Impaired glymphatic function as a biomarker for subjective cognitive decline: An exploratory dual cohort study.

BACKGROUND: Subjective cognitive decline (SCD) has been recognized as a potential risk stage for progression to Alzheimer's disease (AD), while glymphatic dysfunction is considered an important characteristic of AD. We hypothesize that glymphatic dysfunction occurs during the SCD stage, aiming to discover potential biomarkers for SCD. METHODS: Participants from two independent studies, Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 654) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 650), representing different ethnicities and disease stages, were included to assess glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: Abnormal glymphatic function occurs during the SCD stage, with the ALPS index demonstrating excellent classification performance for SCD and normal controls (area under the receiver operating characteristic curve [AUC]SILCODE = 0.816, AUCADNI = 0.797). Lower ALPS index indicates higher risk of cognitive progression, which is negatively correlated with Subjective Cognitive Decline Questionnaire 9 scores and amyloid positron emission tomography burden. DISSCUSION: Our study suggests the ALPS index has the potential to serve as a biomarker for SCD. HIGHLIGHTS: Glymphatic function characterized by the analysis along the perivascular space (ALPS) index becomes abnormal in subjective cognitive decline (SCD), the earliest symptomatic manifestation and preclinical stage of Alzheimer's disease (AD). The ALPS index demonstrates excellent classification performance for SCD and normal controls in the East Asian and Western cohorts. Participants with a lower ALPS index show a higher risk of clinical progression. The ALPS index is closely associated with serval cognitive scales and amyloid beta burden.

A prediction model based on deep learning and radiomics features of DWI for the assessment of microsatellite instability in endometrial cancer.

BACKGROUND: To explore the efficacy of a prediction model based on diffusion-weighted imaging (DWI) features extracted from deep learning (DL) and radiomics combined with clinical parameters and apparent diffusion coefficient (ADC) values to identify microsatellite instability (MSI) in endometrial cancer (EC). METHODS: This study included a cohort of 116 patients with EC, who were subsequently divided into training (n = 81) and test (n = 35) sets. From DWI, conventional radiomics features and convolutional neural network-based DL features were extracted. Random forest (RF) and logistic regression were adopted as classifiers. DL features, radiomics features, clinical variables, ADC values, and their combinations were applied to establish DL, radiomics, clinical, ADC, and combined models, respectively. The predictive performance was evaluated through the area under the receiver operating characteristic curve (AUC), total integrated discrimination index (IDI), net reclassification index (NRI), calibration curves, and decision curve analysis (DCA). RESULTS: The optimal predictive model, based on an RF classifier, comprised four DL features, three radiomics features, two clinical variables, and an ADC value. In the training and test sets, this model exhibited AUC values of 0.989 (95% CI: 0.935-1.000) and 0.885 (95% CI: 0.731-0.967), respectively, demonstrating different degrees of improvement compared with the clinical, DL, radiomics, and ADC models (AUC-training = 0.671, 0.873, 0.833, and 0.814, AUC-test = 0.685, 0.783, 0.708, and 0.713, respectively). The NRI and IDI analyses revealed that the combined model resulted in improved risk reclassification of the MSI status compared to the clinical, radiomics, DL, and ADC models. The calibration curves and DCA indicated good consistency and clinical utility of this model, respectively. CONCLUSIONS: The predictive model based on DWI features extracted from DL and radiomics combined with clinical parameters and ADC values could effectively assess the MSI status in EC.

Relationships of the adversity quotient subtypes of nursing interns with depression, coping styles, positive psychological capital, and professional adaptability: a cross-sectional study.

BACKGROUND: Nursing interns encounter numerous professional pressures during clinical practice. Assessing adversity quotient levels and understanding the influencing factors are crucial for supporting students' seamless transition to professional nurses. PURPOSE: This study examined the adversity quotient subtypes of nursing interns and explored the relationships between adversity quotient and depression, coping styles, positive psychological capital, and professional adaptability. METHODS: This study employed a cross-sectional research design, involving a survey of 287 nursing interns in five general hospitals in Shanghai, China. Latent profile analysis was conducted to explore the subtypes of adversity quotient with the four domains as input variables. Multinomial logistic regression models and multiple correspondence analysis were used for subsequent data analysis. RESULTS: The average adversity quotient score of the nursing interns was 116.63 ± 32.22. A three-profile solution was obtained based on the latent profile analysis results. Three distinct subtypes emerged: a high-adversity quotient subtype (n = 50, 17.4%), a medium-adversity quotient subtype (n = 189, 65.9%), and a relatively low-adversity quotient subtype (n = 48, 16.7%). Multinomial logistic regression revealed that nursing interns in the high-adversity quotient subtype tended to be male, and had higher scores for positive psychological capital, negative coping style, and professional adaptability (p < 0.05). CONCLUSION: Most of the nursing interns were in the medium adversity quotient subtype. Gender, positive psychological capital, negative coping style and professional adaptability were all significantly related to the adversity quotient. Boosting the positive psychological capital of nursing interns is an effective way to improve the adversity quotient.

Abundance, characteristics and ecological risk assessment of microplastics in ship ballast water in ports around Liaodong Peninsula, China.

The development of the shipping industry has led to a large volume of ballast water discharge annually. This accelerates pollutants' transfer and dispersion, such as microplastics. Currently, empirical data on microplastics in ballast water are rarely available. This study innovatively investigated the abundance, morphological characteristics (particle size, shape, and color), and polymer composition of microplastics in ballast water from ports surrounding the Liaodong Peninsula. The results revealed that the average abundance of microplastics in 13 ships' ballast water was 6071.30 ± 1313.85 items/m3. Notably, the small microplastics (0.06-2.50 mm) were most abundant, accounting for 94.52 % of the total microplastics. Transparent, fiber, and polyethylene glycol terephthalate were the most prevalent color, shape, and polymer composition of microplastics detected in the ballast water. The risk assessment indicated that these microplastics present ecological risks to organisms. These findings suggest that ship ballast water is the potential "hotspot" for marine microplastics transport.

Differences in gray matter atrophy and functional connectivity between motor subtypes of Parkinson's disease.

Parkinson's disease (PD) patients with postural gait abnormalities exhibit poorer motor function scores, more severe non-motor symptoms, faster cognitive function deterioration, and a less favorable response to drugs and surgery compared to PD patients with tremor. This discrepancy is believed to be associated with more pronounced gray matter atrophy and abnormal functional connectivity. To investigate the distinctive pathological mechanisms between PD subtypes, we examined gray matter volume (GMV) and functional connectivity in patients with Parkinson's disease presenting with postural instability/gait difficulty (PD-PIGD), patients with tremor-dominant Parkinson's disease (PD-TD), and healthy controls. Voxel-based morphometry (VBM) of T1-weighted images was conducted to compare GMV among 64 PD-PIGD patients, 44 PD-TD patients, and 32 controls. Subsequently, functional connectivity within regions showing reduced GMV was compared across the groups. We analyzed whether differences among the groups were associated with clinical characteristics and neuroimaging biomarkers using partial correlation and binary logistic regression. Our comparison between PD-PIGD and PD-TD patients revealed a link between PD-PIGD and more extensive frontotemporal atrophy, potentially indicating increased basal ganglia activity accompanied by decreased cerebellum activity. Furthermore, in addition to the smaller GMV in the left middle temporal gyrus, the increased functional connectivity between this brain region and the right caudate was also the independent risk factor for PD-PIGD. In addition, we compared brain network connectivity between the PIGD and TD subtypes, using an independent component analysis (ICA). We found that Compared to PD-TD, PD-PIGD patients showed an enhanced sensorimotor network (SMN) around the left supplementary motor area. These findings suggest that severe gray matter atrophy and abnormal functional connectivity and brain networks may serve as pathophysiological mechanisms distinguishing PD-PIGD patients from other subtypes.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

INTRODUCTION: Subjective cognitive decline (SCD) in amyloid-positive (Aß+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models. RESULTS: In the combined and stratified cohorts, Aß+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aß- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION: Aß+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. HIGHLIGHTS: SCD in amyloid-positive (Aß+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aß+ older adults with SCD could be a target population for interventional trials.

Proton-Induced Reversible Spin-State Switching in Octanuclear FeIII Spin-Crossover Metal-Organic Cages.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, FeIII-based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel FeIII MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active FeIII cages and feature an atypical {FeN6}-type coordination sphere, uncommon for FeIII SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these FeIII MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

A Flexible Capacitive Pressure Sensor with Adjustable Detection Range Based on the Inflatable Dielectric Layer for Human-Computer Interaction.

As an essential component in wearable electronic devices and intelligent robots, flexible pressure sensors have enormous application value in fields such as healthcare, human-computer interaction, and intelligent perception. However, due to the complex and ever-changing pressure loads borne by sensors in different application scenarios, this also puts great demands on the flexible response and adjustment ability of a sensor's detection range. Therefore, developing a flexible pressure sensor with a wide and adjustable detection range, which can be applied flexibly under different pressure loads, is also a major challenge in current research. In this paper, we propose a flexible pressure sensor with a wide and adjustable detection range based on an inflatable adjustable safety airbag as the dielectric layer. This sensor uses inflatable airbags prepared using 3D printing technology and silicone reverse molding technology as the dielectric layer and achieves high sensitivity (0.6 kPa-1 to 1.19 kPa-1), wide detection range (220-1500 kPa), and flexible performance applicability by adjusting the air pressure inside the dielectric layer. At the same time, its simple production process, convenient production, fast response time (100 ms), and good stability provide the possibility for the flexible application of sensors in different pressure detection. The experimental results indicate that the sensor has enormous potential for applications in wearable devices, healthcare, human-computer interaction, and intelligent perception recognition.

Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Distribution characteristics and ecological risk analysis of microplastics in sediments and effluents related to offshore oil and gas activities in the Bohai Sea, China.

Oil and gas activities are sources of marine microplastics (MPs) but have received less attention globally. This study assessed the distribution characteristics and ecological risks of MPs in 31 sediment samples and effluent samples of 5 oil and gas platforms related to offshore oil and gas activities in the Bohai Sea. The results showed that the mean abundance of MPs in sediment, produced water, and domestic sewage was 205.7 ± 151.5 items/kg d.w., 18 ± 11 items/L, and 26 ± 39 items/L, respectively. The MPs in sediments and effluents were dominated by transparent, rayon, and fibers <1 mm. Oil and gas activities may influence the abundance of MPs in the sediments. The sediments in the area were at a low level of risk, but some samples exhibited indexes beyond low levels. The mass of MPs carried by the effluents from oil and gas platforms in the Bohai Sea was less than that of other sources.

Chromene meroterpenoids from Rhododendron dauricum L. and their anti-inflammatory effects.

Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5-8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (-)-rhodonoid E (9b), (+)-confluentin (10a), and (-)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC50 values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 µM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, ß-unsaturated ketone carbonyl and Δ12(13) double bond functionalities exhibited enhanced anti-inflammatory properties.

Enhancing mechanical and water barrier properties of starch film using chia mucilage.

Biodegradable packaging materials are increasingly being investigated due to rising concerns about food safety and environmental conservation. This study examines the incorporation of chia mucilage (CM) into starch-based films using the casting method, aiming to understand its effects on the structure and functionality of the films. CM, an anionic heteropolysaccharide, is hypothesized to enhance the mechanical and barrier properties of the films through polymer interactions and hydrogen bonding. Our findings confirm that CM incorporation results in films with uniformly smooth surfaces, indicating high compatibility and homogeneity within the starch matrix. Notably, CM improves film transparency and crystallinity. Mechanical assessments show a remarkable elevation in tensile strength, soaring from 5.21 MPa to 12.38 MPa, while elongation at break decreases from 61.73 % to 31.42 %, indicating a trade-off between strength and flexibility. Additionally, water solubility decreases from 57.97 % to 41.40 %, and water vapor permeability is reduced by 30 % with CM loading. These results highlight the role of CM in facilitating the formation of a dense, interconnected polymeric network within the starch matrix. Given the soluble dietary fiber nature of CM, the CS/CM (corn starch/chia mucilage) blended films are expected to be safe for food packaging and applicable as edible films with health benefits.

Comprehensive analysis of immune-related lncRNAs in AML patients uncovers potential therapeutic targets and prognostic biomarkers.

Purpose: The objective of this study was to provide theoretically feasible strategies by understanding the relationship between the immune microenvironment and the diagnosis and prognosis of AML patients. To this end, we built a ceRNA network with lncRNAs as the core and analyzed the related lncRNAs in the immune microenvironment by bioinformatics analysis. Methods: AML transcriptome expression data and immune-related gene sets were obtained from TCGA and ImmPort. Utilizing Pearson correlation analysis, differentially expressed immune-related lncRNAs were identified. Then, the LASSO-Cox regression analysis was performed to generate a risk signature consisting immune-related lncRNAs. Accuracy of signature in predicting patient survival was evaluated using univariate and multivariate analysis. Next, GO and KEGG gene enrichment and ssGSEA were carried out for pathway enrichment analysis of 183 differentially expressed genes, followed by drug sensitivity and immune infiltration analysis with pRRophetic and CIBERSORT, respectively. Cytoscape was used to construct the ceRNA network for these lncRNAs. Results: 816 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by multivariate Cox and stepwise regression analysis contained 12 lncRNAs engaged in tumor apoptotic and metastatic processes: LINC02595, HCP5, AC020934.2, AC008770.3, LINC01770, AC092718.4, AL589863.1, AC131097.4, AC012368.1, C1RL-AS1, STARD4-AS1, and AC243960.1. Based on this predictive model, high-risk patients exhibited lower overall survival rates than low-risk patients. Signature lncRNAs showed significant correlation with tumor-infiltrating immune cells. In addition, significant differences in PD-1/PD-L1 expression and bleomycin/paclitaxel sensitivity were observed between risk groups. Conclusion: LncRNAs related to immune microenvironment were prospective prognostic and therapeutic options for AML.

An elastic single crystal composed of one-dimensional chiral coordination polymers.

A single crystal composed of one-dimensional coordinated polymers, [CdCl2(1-methyl-2-pyridone)]n, has been synthesized and characterized. This compound exhibits outstanding elastic bending due to the molecular spring nature of the CdCl2 coordination framework and weak intermolecular interactions between the coordination chains. Owing to the helical arrangement of organic ligands surrounding the coordination structure, the compound crystallizes in a chiral space group. As a result, it displays compelling circular dichroism spectra and second harmonic generation properties.

Fluorescence Sensors for the Detection of L-Histidine Based on Silver Nanoclusters Modulated by Copper Ions.

In this study, Cu2+ modulated silver nanoclusters were constructed for the turn-on, label-free detection of L-histidine. Six Ag NCs protected by oligonucleotides (DNA-Ag NCs) were tested in a series of experiments. Finally, A-DAN-Ag NCs were chosen as the best candidate due to their excellent fluorescent properties. The fluorescence of A-DAN-Ag NCs was quenched using Cu2+ through energy or electron transfer. However, quenched fluorescence could be restored dramatically in the presence of L-histidine due to Cu2+ liberation from A-DAN-Ag NCs and because of the chelation between the imidazole group of L-histidine and Cu2+. The proposed sensor exhibited high selectivity towards L-histidine over other amino acids, with a limit of detection (LOD) of 0.096 µM ranging from 0 to 8 µM. The proposed sensor succeeded in detecting L-histidine in diluted human urine. Therefore, the sensor has promising practical applications in biological systems.

A Bayesian Change Point Model for Dynamic Alternative Transcription Start Site Usage During Cellular Differentiation.

ABSTRACT An alternative transcription start site (ATSS) is a major driving force for increasing the complexity of transcripts in human tissues. As a transcriptional regulatory mechanism, ATSS has biological significance. Many studies have confirmed that ATSS plays an important role in diseases and cell development and differentiation. However, exploration of its dynamic mechanisms remains insufficient. Identifying ATSS change points during cell differentiation is critical for elucidating potential dynamic mechanisms. For relative ATSS usage as percentage data, the existing methods lack sensitivity to detect the change point for ATSS longitudinal data. In addition, some methods have strict requirements for data distribution and cannot be applied to deal with this problem. In this study, the Bayesian change point detection model was first constructed using reparameterization techniques for two parameters of a beta distribution for the percentage data type, and the posterior distributions of parameters and change points were obtained using Markov Chain Monte Carlo (MCMC) sampling. With comprehensive simulation studies, the performance of the Bayesian change point detection model is found to be consistently powerful and robust across most scenarios with different sample sizes and beta distributions. Second, differential ATSS events in the real data, whose change points were identified using our method, were clustered according to their change points. Last, for each change point, pathway and transcription factor motif analyses were performed on its differential ATSS events. The results of our analyses demonstrated the effectiveness of the Bayesian change point detection model and provided biological insights into cell differentiation.

Tetraphenylene-based semiconductive metal-organic framework crystals for direct X-ray detection and imaging.

MOFs have good potential for X-ray detection, but direct X-ray detection in single crystal form is rarely reported. In this work, we successfully synthesized Pb-TCPE, and the single crystal achieves a low detection limit and high detection sensitivity of 4812.6 µC Gyair-1 cm-2, which exhibits great potential for X-ray detection and imaging.

Targeted drug-loaded peptides induce tumor cell apoptosis and immunomodulation to increase antitumor efficacy.

Immunotherapy is an emerging approach for the treatment of solid tumors. Although chemotherapy is generally considered immunosuppressive, specific chemotherapeutic agents can induce tumor immunity. In this study, we developed a targeted, acid-sensitive peptide nanoparticle (DT/Pep1) to deliver doxorubicin (DOX) and triptolide (TPL) to breast cancer cells via the enhanced permeability and retention (EPR) effect and the breast cancer-targeting effect of peptide D8. Compared with administration of the free drugs, treatment with the DT/Pep1 system increased the accumulation of DOX and TPL at the tumor site and achieved deeper penetration into the tumor tissue. In an acidic environment, DT/Pep1 transformed from spherical nanoparticles to aggregates with a high aspect ratio, which successfully extended the retention of the drugs in the tumor cells and bolstered the anticancer effect. In both in vivo and in vitro experiments, DT/Pep1 effectively blocked the cell cycle and induced apoptosis. Importantly, the DT/Pep1 system efficiently suppressed tumor development in mice bearing 4T1 tumors while simultaneously promoting immune system activation. Thus, the results of this study provide a system for breast cancer therapy and offer a novel and promising platform for peptide nanocarrier-based drug delivery.

[Exploring the Role of PCDHGB4 in the Occurrence of Lung Squamous Cell Carcinoma Based on Bioinformatics Analysis].

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods. METHODS: The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes. RESULTS: Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways. CONCLUSIONS: The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

Investigation of HLA susceptibility alleles and genotypes with hematological disease among Chinese Han population.

Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance.