Chip-Based Electronic System for Quantum Key Distribution.

Quantum Key Distribution (QKD) has garnered significant attention due to its unconditional security based on the fundamental principles of quantum mechanics. While QKD has been demonstrated by various groups and commercial QKD products are available, the development of a fully chip-based QKD system, aimed at reducing costs, size, and power consumption, remains a significant technological challenge. Most researchers focus on the optical aspects, leaving the integration of the electronic components largely unexplored. In this paper, we present the design of a fully integrated electrical control chip for QKD applications. The chip, fabricated using 28 nm CMOS technology, comprises five main modules: an ARM processor for digital signal processing, delay cells for timing synchronization, ADC for sampling analog signals from monitors, OPAMP for signal amplification, and DAC for generating the required voltage for phase or intensity modulators. According to the simulations, the minimum delay is 11ps, the open-loop gain of the operational amplifier is 86.2 dB, the sampling rate of the ADC reaches 50 MHz, and the DAC achieves a high rate of 100 MHz. To the best of our knowledge, this marks the first design and evaluation of a fully integrated driver chip for QKD, holding the potential to significantly enhance QKD system performance. Thus, we believe our work could inspire future investigations toward the development of more efficient and reliable QKD systems.

Clinicopathological and molecular characterization of resected lung adenocarcinoma: Correlations with histopathological grading systems in Chinese patients.

PURPOSE: Driver mutations inform lung adenocarcinoma (LUAD) targeted therapy. Association of histopathological attributes and molecular profiles facilitates clinically viable testing platforms. We assessed correlations between LUAD clinicopathological features, mutational landscapes, and two grading systems among Chinese cases. METHODS: 79 Chinese LUAD patients undergoing resection were subjected to targeted sequencing. 68 were invasive nonmucinous adenocarcinoma (INMA), graded via: predominant histologic pattern-based grading system (P-GS) or novel IASLC grading system (I-GS). Driver mutation distributions were appraised and correlated with clinical and pathological data. RESULTS: Compared to INMA, non-INMA exhibited smaller, well-differentiated tumors with higher mucin content. INMA grade correlated with size, lymph invasion (P-GS), and driver/EGFR mutations. Mutational spectra varied markedly between grades, with EGFR p.L858R and exon 19 deletion mutations predominating in lower grades; while high-grade P-GS tumors often harbored EGFR copy number variants and complex alterations alongside wild-type cases. I-GS upgrade of P-GS grade 2 to grade 3 was underpinned by ≥20 % high-grade regions bearing p.L858R or ALK fusions. Both systems defined tumors of distinctive phenotypic attributes and molecular genotypes. CONCLUSIONS: INMA represent larger, mucin-poor, molecularly heterogeneous LUAD with divergent grade-specific mutation profiles. Stronger predictor of clinicopathological attributes and driver mutations, P-GS stratification offers greater accuracy for molecular testing. A small panel encompassing EGFR and ALK captures the majority of P-GS grade 1/2 mutations whereas expanded panels are optimal for grade 3.

In situ N-doping engineered biochar catalysts for oxidation degradation of sulfadiazine via nonradical pathways: Singlet oxygen and electron transfer.

Understanding the structure of non-metallic heteroatom-doped carbon catalysts and the subsequent degradation of new pollutants is crucial for designing more efficient carbon catalysts. Environmentally friendly in situ N-doped biochar catalysts were prepared for peroxymonosulfate (PMS) activation and sulfadiazine (SDZ) degradation. The acid washing process and calcination temperature of catalyst increased π-π* shake up, graphitic N percentage, specific surface area and defects, promoting the transformation of pollutant degradation mechanism from radical pathway to non-radical pathway. 100 % of the SDZ with the initial concentration of 10 mg/L was quickly degraded within 60 min using 0.2 g/L catalysts and 0.5 mM PMS. Excellent catalytic performance was attributed to singlet oxygen and electron transfer-dominated non-radical pathways. The four potential degradation pathways of SDZ were proposed, and toxicity predication indicated that overall biotoxicity of the intermediates during SDZ degradation was decreased. This research deepens our understanding of the mechanisms of non-radical pathways and guides the synthesis of carbon-based catalysts.

Radiation-induced exosomes promote oral squamous cell carcinoma progression via enhancing SLC1A5-glutamine metabolism.

BACKGROUND: Radiotherapy (RT) can drive cancer cells to enter a state of cellular senescence in which cells can secrete senescence-associated secretory phenotype (SASP) and produce small extracellular vesicles (sEVs) to interact with cells in the tumor microenvironment (TME). Tumor-derived sEVs that are taken up by recipient cells contribute to cancer cell metabolic plasticity, resistance to anticancer therapy, and adaptation to the TME. However, how radiation-induced sEVs support oral squamous cell carcinoma (OSCC) progression remains unclear. METHODS: Beta-galactosidase staining and SASP mRNA expression analysis were used to evaluate the senescence-associated activity of OSCC cells after irradiation. Nanoparticle tracking analysis was performed to identify radiation-induced sEVs. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to explore changes in the levels of proteins in radiation-induced sEVs. Cell Counting Kit-8 and colony formation assays were performed to investigate the function of radiation-induced SASP and sEVs in vitro. A xenograft tumor model was established to investigate the functions of radiation-induced sEVs and V-9302 in vivo as well as the underlying mechanisms. Bioinformatics analysis was performed to determine the relationship between glutamine metabolism and OSCC recurrence. RESULTS: We determined that the radiation-induced SASP triggered OSCC cell proliferation. Additionally, radiation-induced sEVs exacerbated OSCC cell malignancy. LC-MS/MS and bioinformatics analyses revealed that SLC1A5, which is a cellular receptor that participates in glutamine uptake, was significantly enriched in radiation-induced sEVs. In vitro and in vivo, inhibiting SLC1A5 could block the oncogenic effects of radiation-induced sEVs in OSCC. CONCLUSION: Radiation-induced sEVs might promote the proliferation of unirradiated cancer cells by enhancing glutamine metabolism; this might be a novel molecular mechanism underlying radiation resistance in OSCC patients.

Mechanosensitive Ion Channels Piezo1 and Piezo2 in Vivo Mediate Motor Response During Transcranial Focused Ultrasound Stimulation of Rodent Cerebral Motor Cortex.

OBJECTIVE: Transcranial focused ultrasound (tFUS) neuromodulation offers a noninvasive, safe, deep brain stimulation with high precision, presenting potential in understanding neural circuits and treating brain disorders. This in vivo study investigated the mechanism of tFUS in activating the opening of the mechanosensitive ion channels Piezo1 and Piezo2 in the mouse motor cortex to induce motor responses. METHODS: Piezo1 and Piezo2 were knocked down separately in the mouse motor cortex, followed by EMG and motor cortex immunofluorescence comparisons before and after knockdown under tFUS stimulation. RESULTS: The results demonstrated that the stimulation-induced motor response success rates in Piezo knockdown mice were lower compared to the control group (Piezo1 knockdown: 57.63% ± 14.62%, Piezo2 knockdown: 73.71% ± 13.10%, Control mice: 85.69% ± 10.23%). Both Piezo1 and Piezo2 knockdowns showed prolonged motor response times (Piezo1 knockdown: 0.62 ± 0.19 s, Piezo2 knockdown: 0.60 ± 0.13 s, Control mice: 0.44 ± 0.12 s) compared to controls. Additionally, Piezo knockdown animals subjected to tFUS showed reduced immunofluorescent c-Fos expression in the target area when measured in terms of cells per unit area compared to the control group. CONCLUSION: This in vivo study confirms the pivotal role of Piezo channels in tFUS-induced neuromodulation, highlighting their influence on motor response efficacy and timing. SIGNIFICANCE: This study provides insights into the mechanistic underpinnings of noninvasive brain stimulation techniques and opens avenues for developing targeted therapies for neural disorders.

Does working memory training improve emotion regulation and reduce internalizing symptoms? A pair of three-level meta-analyses.

BACKGROUND: Emotional dysfunction is a core feature of many mental disorders. Working memory training (WM-T) is promising to improve emotion regulation and reduce internalizing symptoms (anxiety and depressive symptoms), but the results are mixed. Therefore, we conducted meta-analyses to clarify these mixed results. METHODS: We searched Web of Science, PubMed, ScienceDirect, and EBSCO to identify relevant studies and screened the references. The effect size was calculated using Hedges' g. Three-level, random-effects models were run using metafor in R. RESULTS: The current study included 44 articles, of which 29 were involved with emotion regulation, and 30 were involved with internalizing symptoms. The results showed that WM-T could yield emotional benefits, but the benefits were confined to enhancing explicit emotional regulation capacity and reducing anxiety symptoms. For the meta-analysis regarding the effect of WM-T on emotion regulation, there was no significant moderator. For the meta-analysis regarding the effect of WM-T on internalizing symptoms, the emotional valence of the material and control group were statistically significant moderators. CONCLUSION: WM-T could yield certain emotional effects, but only to improve explicit emotion regulation capacity and reduce anxiety symptoms. In addition, some measures could enhance the effect, such as targeting specific populations, increasing the number of training sessions (≥15) or duration (>450 minutes), using negative material, and using n-back training tasks.

Immunogenicity and safety of concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine in Chinese adults: An open-label, randomized, controlled trial.

The immunogenicity and safety of the concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine (Split Virion) (QIIV) in Chinese adults are unclear. In this open-label, randomized controlled trial, participants aged ≥ 18 years were recruited. Eligible healthy adults were randomly assigned (1:1) to receive QIIV at the same time as the first dose of COVID-19 vaccine (simultaneous-group) or 14 days after the second dose of COVID-19 vaccine (non-simultaneous-group). The primary outcome was to compare the difference in immunogenicity of QIIV (H1N1, H3N2, Yamagata, and Victoria) between the two groups. A total of 299 participants were enrolled, 149 in the simultaneous-group and 150 in the non-simultaneous-group. There were no significant differences in geometric mean titer (GMT) [H1N1: 386.4 (95%CI: 299.2-499.0) vs. 497.4 (95%CI: 377.5-655.3); H3N2: 66.9 (95%CI: 56.1-79.8) vs. 81.4 (95%CI: 67.9-97.5); Yamagata: 95.6 (95%CI: 79.0-115.8) vs. 74.3 (95%CI: 58.6-94.0); and Victoria: 48.5 (95%CI: 37.6-62.6) vs. 65.8 (95%CI: 49.0-88.4)] and seroconversion rate (H1N1: 87.5% vs. 90.1%; H3N2: 58.1% vs. 62.0%; Yamagata: 75.0% vs. 64.5%; and Victoria: 55.1% vs. 62.8%) of QIIV antibodies between the simultaneous and non-simultaneous groups. For the seroprotection rate of QIIV antibodies, a higher seroprotection rate of Yamagata antibody was observed only in the simultaneous-group than in the non-simultaneous-group [86.0% vs. 76.0%, p = .040]. In addition, no significant difference in adverse events was observed between the two groups (14.2% vs. 23.5%, p = .053). In conclusion, no immune interference or safety concerns were found for concomitant administration of COVID-19 vaccine with QIIV in adults aged ≥ 18 years.

Closing the gap: Solving complex medically relevant genes at scale.

Comprehending the mechanism behind human diseases with an established heritable component represents the forefront of personalized medicine. Nevertheless, numerous medically important genes are inaccurately represented in short-read sequencing data analysis due to their complexity and repetitiveness or the so-called 'dark regions' of the human genome. The advent of PacBio as a long-read platform has provided new insights, yet HiFi whole-genome sequencing (WGS) cost remains frequently prohibitive. We introduce a targeted sequencing and analysis framework, Twist Alliance Dark Genes Panel (TADGP), designed to offer phased variants across 389 medically important yet complex autosomal genes. We highlight TADGP accuracy across eleven control samples and compare it to WGS. This demonstrates that TADGP achieves variant calling accuracy comparable to HiFi-WGS data, but at a fraction of the cost. Thus, enabling scalability and broad applicability for studying rare diseases or complementing previously sequenced samples to gain insights into these complex genes. TADGP revealed several candidate variants across all cases and provided insight into LPA diversity when tested on samples from rare disease and cardiovascular disease cohorts. In both cohorts, we identified novel variants affecting individual disease-associated genes (e.g., IKZF1, KCNE1). Nevertheless, the annotation of the variants across these 389 medically important genes remains challenging due to their underrepresentation in ClinVar and gnomAD. Consequently, we also offer an annotation resource to enhance the evaluation and prioritization of these variants. Overall, we can demonstrate that TADGP offers a cost-efficient and scalable approach to routinely assess the dark regions of the human genome with clinical relevance.

Molecularly Thin 2D Organic Single Crystals: A New Platform for High-Performance Polarization-Sensitive Phototransistors.

The inherent linear dichroism (LD), high absorption, and solution processability of organic semiconductors hold immense potential to revolutionize polarized light detection. However, the disordered molecular packing inherent to polycrystalline thin films obscures their intrinsic diattenuation, resulting in diminished polarization sensitivity. In this study, we develop filter-free organic polarization-sensitive phototransistors (PSPs) with both a high linear dichroic ratio (LDR) and exceptional photosensitivity utilizing molecularly thin dithieno[3,2-b:2',3'-d]thiophene derivatives (DTT-8) two-dimensional molecular crystals (2DMCs) as the active layer. The orderly molecular packing in 2DMCs amplifies the inherent LD, and their molecular-scale thickness enables complete channel depletion, significantly reducing the dark current. As a result, PSPs with an impressive LDR of 3.15 and a photosensitivity reaching 3.02 × 106 are obtained. These findings present a practical demonstration of using the polarization angle as an encryption key in optical communication, showcasing the potential of 2DMCs as a viable and promising category of semiconductors for filter-free, polarization-sensitive photodetectors.

Evaluating the accuracy and relevance of ChatGPT responses to frequently asked questions regarding total knee replacement.

BACKGROUND: Chat Generative Pretrained Transformer (ChatGPT), a generative artificial intelligence chatbot, may have broad applications in healthcare delivery and patient education due to its ability to provide human-like responses to a wide range of patient queries. However, there is limited evidence regarding its ability to provide reliable and useful information on orthopaedic procedures. This study seeks to evaluate the accuracy and relevance of responses provided by ChatGPT to frequently asked questions (FAQs) regarding total knee replacement (TKR). METHODS: A list of 50 clinically-relevant FAQs regarding TKR was collated. Each question was individually entered as a prompt to ChatGPT (version 3.5), and the first response generated was recorded. Responses were then reviewed by two independent orthopaedic surgeons and graded on a Likert scale for their factual accuracy and relevance. These responses were then classified into accurate versus inaccurate and relevant versus irrelevant responses using preset thresholds on the Likert scale. RESULTS: Most responses were accurate, while all responses were relevant. Of the 50 FAQs, 44/50 (88%) of ChatGPT responses were classified as accurate, achieving a mean Likert grade of 4.6/5 for factual accuracy. On the other hand, 50/50 (100%) of responses were classified as relevant, achieving a mean Likert grade of 4.9/5 for relevance. CONCLUSION: ChatGPT performed well in providing accurate and relevant responses to FAQs regarding TKR, demonstrating great potential as a tool for patient education. However, it is not infallible and can occasionally provide inaccurate medical information. Patients and clinicians intending to utilize this technology should be mindful of its limitations and ensure adequate supervision and verification of information provided.

Multiple ultrasonic parametric imaging for the detection and monitoring of high-intensity focused ultrasound ablation.

Numerous quantitative ultrasound imaging techniques have demonstrated superior monitoring performance for thermal ablation when compared to conventional ultrasonic B-mode imaging. However, the absence of comparative studies involving various quantitative ultrasound imaging techniques hinders further clinical exploration. In this study, we simultaneously reconstructed ultrasonic Nakagami imaging, ultrasonic horizontally normalized Shannon entropy (hNSE) imaging, and ultrasonic differential attenuation coefficient intercept (DACI) imaging from ultrasound backscattered envelope data collected during high-intensity focused ultrasound ablation treatment. We comprehensively investigated their performance differences through qualitative and quantitative analyses, including the calculation of contrast-to-noise ratios (CNR) for ultrasonic images, receiver operating characteristic (ROC) analysis with corresponding indicators, the analysis of lesion area fitting relationships, and computational time consumption comparison. The mean CNR of hNSE imaging was 10.98 ± 4.48 dB, significantly surpassing the 3.82 ± 1.40 dB (p < 0.001, statistically significant) of Nakagami imaging and the 2.45 ± 0.74 dB (p < 0.001, statistically significant) of DACI imaging. This substantial difference underscores that hNSE imaging offers the highest contrast resolution for lesion recognition. Furthermore, we evaluated the ability of multiple ultrasonic parametric imaging to detect thermal ablation lesions using ROC curves. The area under the curve (AUC) for hNSE was 0.874, exceeding the values of 0.848 for Nakagami imaging and 0.832 for DACI imaging. Additionally, hNSE imaging exhibited the strongest linear correlation coefficient (R = 0.92) in the comparison of lesion area fitting, outperforming Nakagami imaging (R = 0.87) and DACI imaging (R = 0.85). hNSE imaging also performs best in real-time monitoring with each frame taking 6.38 s among multiple ultrasonic parametric imaging. Our findings unequivocally demonstrate that hNSE imaging excels in monitoring HIFU ablation treatment and holds the greatest potential for further clinical exploration.

Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

Background: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). Methods: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively. Results: A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival. Conclusions: These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

Characterization of macrophages in ischemia-reperfusion injury-induced acute kidney injury based on single-cell RNA-Seq and bulk RNA-Seq analysis.

Acute kidney injury (AKI) is a complex disease, with macrophages playing a vital role in its progression. However, the mechanism of macrophage function remains unclear and strategies targeting macrophages in AKI are controversial. To address this issue, we used single-cell RNA-seq analysis to identify macrophage sub-types involved in ischemia-reperfusion-induced AKI, and then screened for associated hub genes using intersecting bulk RNA-seq data. The single-cell and bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) database. Screening of differentially-expressed genes (DEGs) and pseudo-bulk DEG analyses were used to identify common hub genes. Pseudotime and trajectory analyses were performed to investigate the progression of cell differentiation. CellChat analysis was performed to reveal the crosstalk between cell clusters. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify enriched pathways in the cell clusters. Immunofluorescence and RT-PCR were preformed to validate the expression of the identified hub genes. Four hub genes, Vim, S100a6, Ier3, and Ccr1, were identified in the infiltrated macrophages between normal samples and those 3 days after ischemia-reperfusion renal injury (IRI); all were associated with the progression of IRI-induced AKI. Increased expression of Vim, S100a6, Ier3, and Ccr1 in infiltrated macrophages may be associated with inflammatory responses and may mediate crosstalk between macrophages and renal tubular epithelial cells under IRI conditions. Our results reveal that Ier3 may be critical in AKI, and that Vim, S100a6, Ier3, and Ccr1 may act as novel biomarkers and potential therapeutic targets for IRI-induced AKI.

A2M possesses anti-bacterial functions by recruiting and enhancing phagocytosis through GRP78 in an echinoderm.

Alpha-2-macroglobulin (A2M) is an extracellular macromolecule mainly known for its role as a broad-spectrum protease inhibitor in mammals. However, the immune recognition and regulation mechanisms of A2M in invertebrates are still not well investigated. In the current study, the role of sea cucumber Apostichopus japonicus A2M in the regulation of innate immune responses was explored. We found that AjA2M promotes phagocytosis of Vibrio splendidus in coelomocytes of sea cucumber. Then two major functional structural domains of AjA2M, the thioester domain (TED) and the receptor-binding structural domain (RBD) were cloned. It was found that the AjA2M-TED binds to pathogens while causing Vibrio splendidus aggregation; the AjA2M-RBD interacts with the Glucose Regulated Protein 78 (AjGRP78), subsequently AjGRP78 accelerates the degradation of Vibrio splendidus in lysosomes by facilitating polymerisation and rearrangement of the cytoskeleton. Collectively, the findings together suggest that A2M-GRP78 axis mediates immune signaling pathway of phagocytosis and AjA2M has been characterized to play an essential crucial role in antibacterial immune responses of invertebrates.

From pre-clinical to translational brain metastasis research: current challenges and emerging opportunities.

Brain metastasis, characterized by poor clinical outcomes, is a devastating disease. Despite significant mechanistic and therapeutic advances in recent years, pivotal improvements in clinical interventions have remained elusive. The heterogeneous nature of the primary tumor of origin, complications in drug delivery across the blood-brain barrier, and the distinct microenvironment collectively pose formidable clinical challenges in developing new treatments for patients with brain metastasis. Although current preclinical models have deepened our basic understanding of the disease, much of the existing research on brain metastasis has employed a reductionist approach. This approach, which often relies on either in vitro systems or in vivo injection models in young and treatment-naive mouse models, does not give sufficient consideration to the clinical context. Given the translational importance of brain metastasis research, we advocate for the design of preclinical experimental models that take into account these unique clinical challenges and align more closely with current clinical practices. We anticipate that aligning and simulating real-world patient conditions will facilitate the development of more translatable treatment regimens. This brief review outlines the most pressing clinical challenges, the current state of research in addressing them, and offers perspectives on innovative metastasis models and tools aimed at identifying novel strategies for more effective management of clinical brain metastasis.

Membrane-associated RING-CH 7 inhibits stem-like capacities of bladder cancer cells by interacting with nucleotide-binding oligomerization domain containing 1.

BACKGROUND: Cancer stem-like capacities are major factors contributing to unfavorable prognosis. However, the associated molecular mechanisms underlying cancer stem-like cells (CSCs) maintain remain unclear. This study aimed to investigate the role of the ubiquitin E3 ligase membrane-associated RING-CH 7 (MARCH7) in bladder cancer cell CSCs. METHODS: Male BALB/c nude mice aged 4-5 weeks were utilized to generate bladder xenograft model. The expression levels of MARCHs were checked in online databases and our collected bladder tumors by quantitative real-time PCR (q-PCR) and immunohistochemistry (IHC). Next, we evaluated the stem-like capacities of bladder cancer cells with knockdown or overexpression of MARCH7 by assessing their spheroid-forming ability and spheroid size. Additionally, we conducted proliferation, colony formation, and transwell assays to validate the effects of MARCH7 on bladder cancer CSCs. The detailed molecular mechanism of MARCH7/NOD1 was validated by immunoprecipitation, dual luciferase, and in vitro ubiquitination assays. Co-immunoprecipitation experiments revealed that nucleotide-binding oligomerization domain-containing 1 (NOD1) is a substrate of MARCH7. RESULTS: We found that MARCH7 interacts with NOD1, leading to the ubiquitin-proteasome degradation of NOD1. Furthermore, our data suggest that NOD1 significantly enhances stem-like capacities such as proliferation and invasion abilities. The overexpressed MARCH7 counteracts the effects of NOD1 on bladder cancer CSCs in both in vivo and in vitro models. CONCLUSION: Our findings indicate that MARCH7 functions as a tumor suppressor and inhibits the stem-like capacities of bladder tumor cells by promoting the ubiquitin-proteasome degradation of NOD1. Targeting the MARCH7/NOD1 pathway could be a promising therapeutic strategy for bladder cancer patients.

Eosinophil extracellular traps in eosinophilic chronic rhinosinusitis induce Charcot-Leyden crystal formation and eosinophil recruitment.

Eosinophil extracellular traps (EETs) are implicated in various eosinophil-associated diseases; however, their role in chronic rhinosinusitis (CRS) remains unclear. In the present study, 57 CRS patients were enrolled, and immunofluorescence was used to analyze EETs in eosinophilic (eCRS) and non-eosinophilic (Non-eCRS) tissues. MSD was used to examine IL-4, IL-5, and IL-13 concentrations in tissue homogenates. Charcot-Leyden crystals (CLCs) protein expression was detected in PMA, PMA+DNase I, and blank control eosinophils using ELISA. Eotaxin-3 mRNA and protein levels were measured in human nasal epithelial cells (HNECs) cultured with EETs, EETs+DNase I, DNase I, and unstimulated eosinophils using PCR and ELISA. EETs were significantly increased in eCRS tissues compared with Non-eCRS (P<0.001), and correlated with VAS and Lund-Mackay CT scores. IL-5 expression was related to EETs formation (r = 0.738, P<0.001). PMA-stimulated eosinophils exhibited higher CLCs protein levels (P<0.01). Co-culturing HNECs with EETs significantly increased eotaxin-3 mRNA and protein levels (P<0.0001, P<0.001) compared with other groups. The study suggests EETs formation is elevated in eCRS patients and is involved in CLCs formation and chemokine secretion, promoting eosinophilic inflammation.

Effects of immunogenic cell death-inducing chemotherapeutics on the immune cell activation and tertiary lymphoid structure formation in melanoma.

Background: The infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas. Methods: Doxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining. Results: Doxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells. Conclusions: These results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

Algorithmic detection of sleep-disordered breathing using respiratory signals: a systematic review.

Background and Objective. Sleep-disordered breathing (SDB) poses health risks linked to hypertension, cardiovascular disease, and diabetes. However, the time-consuming and costly standard diagnostic method, polysomnography (PSG), limits its wide adoption and leads to underdiagnosis. To tackle this, cost-effective algorithms using single-lead signals (like respiratory, blood oxygen, and electrocardiogram) have emerged. Despite respiratory signals being preferred for SDB assessment, a lack of comprehensive reviews addressing their algorithmic scope and performance persists. This paper systematically reviews 2012-2022 literature, covering signal sources, processing, feature extraction, classification, and application, aiming to bridge this gap and provide future research references.Methods. This systematic review followed the registered PROSPERO protocol (CRD42022385130), initially screening 342 papers, with 32 studies meeting data extraction criteria.Results. Respiratory signal sources include nasal airflow (NAF), oronasal airflow (OAF), and respiratory movement-related signals such as thoracic respiratory effort (TRE) and abdominal respiratory effort (ARE). Classification techniques include threshold rule-based methods (8), machine learning models (13), and deep learning models (11). The NAF-based algorithm achieved the highest average accuracy at 94.11%, surpassing 78.19% for other signals. Hypopnea detection sensitivity with single-source respiratory signals remained modest, peaking at 73.34%. The TRE and ARE signals proved to be reliable in identifying different types of SDB because distinct respiratory disorders exhibited different patterns of chest and abdominal motion.Conclusions. Multiple detection algorithms have been widely applied for SDB detection, and their accuracy is closely related to factors such as signal source, signal processing, feature selection, and model selection.