GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signal pathway.

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and regulate various physiological and pathological processes. Despite extensive studies, the roles of GPCRs in mouse embryonic stem cells (mESCs) represent a significant data gap. Here, we show that GPR160, a class A member of GPCRs, is dramatically downregulated concurrent with mESC differentiation into embryoid bodies in vitro. Knockdown of GPR160 leads to downregulation of the expression of pluripotency-associated transcription factors and upregulation of the expression of lineage markers, accompanying with the arrest of the mESC cell cycle in the G0/G1 phase. RNA-seq analysis shows that GPR160 participates in the JAK/STAT signaling pathway crucial for maintaining ESC stemness, and the knockdown of GPR160 results in the downregulation of STAT3 phosphorylation level, which in turn is partially rescued by colivelin, a STAT3 activator. Constant with these observations, GPR160 physically interacts with JAK1, and cooperates with leukemia inhibitory factor receptor (LIFR) and gp130 to activate the STAT3 pathway. In summary, our results suggest that GPR160 regulates mESC self-renewal and pluripotency by interacting with the JAK1-LIFR-gp130 complex to mediate the JAK1/STAT3 signaling pathway.

A clinical comparative study of dual LVIS devices and single flow diversion stenting for the treatment of unruptured V3-V4 vertebral artery dissection.

PURPOSE: This study aims to compare the efficacy and safety of using overlapping low-profile visualized intraluminal support (LVIS) devices and flow diversion (FD) for the treatment of unruptured vertebral artery dissection (VAD) in the V3-V4 segments. METHODS: The clinical and imaging data of 71 patients with unruptured VAD in the V3-V4 segments who underwent either dual LVIS stenting (d-LVIS group) or single FD stenting (FD group) at our center from September 2014 to December 2021 were retrospectively analyzed. RESULTS: Immediate postoperative angiography revealed no significant difference in the degree of occlusion between the two groups in treating vertebral artery dissecting aneurysms (with or without noncompact coiling). However, the d-LVIS group had significantly higher fluoroscopy exposure time and total radiation exposure dose compared to the FD group. During the perioperative period, two cases of pontine infarction and one case of acute thrombosis were encountered. One patient died from subarachnoid hemorrhage during the follow-up period. For dissecting the aneurysm, angiographic follow-up (8.56 ± 1.96 months) showed similar healing outcomes between the two groups (with or without noncompact coiling). However, seven patients (7/40, 17.5%) showed poor healing and one patient showed mild in-stent stenosis. For simple dissection, angiographic follow-up (8.78 ± 1.83 months) showed patent lumens in both groups, with all dissections healing well, and two patients having mild in-stent stenosis. CONCLUSION: Both methods could effectively treat unruptured VAD in V3-V4 segments. Nevertheless, simple FD implantation is relatively easier to perform and involves lower radiation exposure.

Membranes with Molecular Gatekeepers for Efficient CO2 Capture and H2 Purification.

The urgent need for CO2 capture and hydrogen energy has attracted great attention owing to greenhouse gas emissions and global warming problems. Efficient CO2 capture and H2 purification with membrane technology will reduce greenhouse gas emissions and help reach a carbon-neutral society. Here, 4-sulfocalix[4]arene (SC), which has an intrinsic cavity, was embedded into the Matrimid membrane as a molecular gatekeeper for CO2 capture and H2 purification. The interactions between SC and the Matrimid polymer chains immobilize SC molecules into the interchain gaps of the Matrimid membrane, and the strong hydrogen and ionic bondings were able to form homogeneous mixed-matrix membranes. The incorporation of the SC molecular gatekeeper with exceptional molecular-sieving properties improved the gas separation performance of the mixed-matrix membranes. Compared with that of the Matrimid membrane, the CO2 permeability of the Matrimid-SC-3% membrane increased from 16.75 to 119.78 Barrer, the CO2/N2 selectivity increased from 29.39 to 106.95, and the CO2/CH4 selectivity increased from 29.91 to 140.92. Furthermore, when the permeability of H2 was increased to 172.20 Barrer, the H2/N2 and H2/CH4 selectivities reached approximately 153.75 and 202.59, respectively, which are far superior to those of most existing Matrimid-based materials. The mixed-matrix membranes also exhibited excellent long-term operation stability, with separation performance for several important gas pairs still overtaking the Robeson upper limit after aging for 400 days.

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study.

BACKGROUND: To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors. METHODS: A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP. RESULTS: The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone. CONCLUSIONS: The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance. TRIAL REGISTRATION: Clinical Trials, NCT03645655. Registered 20 August 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03645655 .

Emissive brightening in molecular graphene nanoribbons by twilight states.

Carbon nanomaterials are expected to be bright and efficient emitters, but structural disorder, intermolecular interactions and the intrinsic presence of dark states suppress their photoluminescence. Here, we study synthetically-made graphene nanoribbons with atomically precise edges and which are designed to suppress intermolecular interactions to demonstrate strong photoluminescence in both solutions and thin films. The resulting high spectral resolution reveals strong vibron-electron coupling from the radial-breathing-like mode of the ribbons. In addition, their cove-edge structure produces inter-valley mixing, which brightens conventionally-dark states to generate hitherto-unrecognised twilight states as predicted by theory. The coupling of these states to the nanoribbon phonon modes affects absorption and emission differently, suggesting a complex interaction with both Herzberg-Teller and Franck- Condon coupling present. Detailed understanding of the fundamental electronic processes governing the optical response will help the tailored chemical design of nanocarbon optical devices, via gap tuning and side-chain functionalisation.

Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

Stem-like CD8 T cells in stage I lung adenocarcinoma as a prognostic biomarker: A preliminary study.

OBJECTIVES: This study aimed to investigate the presence of stem-like CD8 T (CD8 TSL) cells in lung adenocarcinoma (LUAD) and explore their relationships with the clinical outcomes. METHODS: Multiplex immunofluorescence (mIF) was performed to identify CD8 TSL and antigen-presenting cells (APC) in 76 LUAD patients. Differences in the number of CD8 TSL cells based on tumor stage and the spatial relationships between CD8 TSL cells and APC niches were determined. The optimal cutoff value of CD8 TSL cells for predicting survival in patients with stage I LUAD was calculated. RESULTS: CD8 TSL cells were present in all tumors, and their numbers were significantly higher in stage I patients than in stage III patients (P = 0.010); CD8 TSL cells located in the APC niches accounted for 69.7% (53/76) of the hotspot fields. The optimal cutoff value for the number of CD8 TSL cells required to predict the overall survival (OS) in patients with stage I LUAD was 2.5 per 10000 µm2. The median OS and progression-free survival (PFS) in the high-level group (>2.5) were significantly (P < 0.001) longer than those in the low-level group (≤2.5). The number of CD8 TSL cells was an independent prognostic factor for stage I LUAD. Patients with more CD8 TSL cells had a lower risk of death and disease progression than those with less CD8 TSL cells. CONCLUSION: CD8 TSL cells were observed in patients with stages I-III LUAD and might serve as prognostic biomarkers for stage I LUAD.

Diagnostic and prognostic nomograms for laryngeal carcinoma patients with lung metastasis: a SEER-based study.

PURPOSE: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. METHODS: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. RESULTS: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. CONCLUSION: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.

YF17D-based vaccines - standing on the shoulders of a giant.

Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.

Using unsupervised learning to classify inlet water for more stable design of water reuse in industrial parks.

The water reuse facilities of industrial parks face the challenge of managing a growing variety of wastewater sources as their inlet water. Typically, this clustering outcome is designed by engineers with extensive expertise. This paper presents an innovative application of unsupervised learning methods to classify inlet water in Chinese water reuse stations, aiming to reduce reliance on engineer experience. The concept of 'water quality distance' was incorporated into three unsupervised learning clustering algorithms (K-means, DBSCAN, and AGNES), which were validated through six case studies. Of the six cases, three were employed to illustrate the feasibility of the unsupervised learning clustering algorithm. The results indicated that the clustering algorithm exhibited greater stability and excellence compared to both artificial clustering and ChatGPT-based clustering. The remaining three cases were utilized to showcase the reliability of the three clustering algorithms. The findings revealed that the AGNES algorithm demonstrated superior potential application ability. The average purity in six cases of K-means, DBSCAN, and AGNES were 0.947, 0.852, and 0.955, respectively.

TacPrint: Visualizing the Biomechanical Fingerprint in Table Tennis.

Table tennis is a sport that demands high levels of technical proficiency and body coordination from players. Biomechanical fingerprints can provide valuable insights into players' habitual movement patterns and characteristics, allowing them to identify and improve technical weaknesses. Despite the potential, few studies have developed effective methods for generating such fingerprints. To address this gap, we propose TacPrint, a framework for generating a biomechanical fingerprint for each player. TacPrint leverages machine learning techniques to extract comprehensive features from biomechanics data collected by inertial measurement units (IMU) and employs the attention mechanism to enhance model interpretability. After generating fingerprints, TacPrint provides a visualization system to facilitate the exploration and investigation of these fingerprints. In order to validate the effectiveness of the framework, we designed an experiment to evaluate the model's performance and conducted a case study with the system. The results of our experiment demonstrated the high accuracy and effectiveness of the model. Additionally, we discussed the potential of TacPrint to be extended to other sports.

Effects of cold plasma pretreatment combined with sodium periodate on property enhancement of dialdehyde starch prepared using native maize starch.

This study represents the inaugural investigation into the effect of cold plasma (CP) pretreatment combined with sodium periodate on the preparation of dialdehyde starch (DAS) from native maize starch and its consequent effects on the properties of DAS. The findings indicate that the maize starch underwent etching by the plasma, leading to an increase in the particle size of the starch, which in turn weakened the rigid structure of the starch and reduced its crystallinity. Concurrently, the plasma treatment induced cleavage of the starch molecular chain, resulting in a decrease in the viscosity of the starch and an enhancement of its fluidity. These alterations facilitated an increased contact area between the starch and the oxidising agent sodium periodate, thereby augmenting the efficiency of the DAS preparation reaction. Consequently, the aldehyde group content was elevated by 9.98 % compared to the conventional DAS preparation methodology. Therefore, CP could be an efficient and environmentally friendly non-thermal processing method to assist starch oxidation for DAS preparation and property enhancement.

Safety and Efficacy of LVIS Jr Stent-assisted Coiling of Intracranial Aneurysms in Small-diameter Parent Arteries : A Single-center Experience.

OBJECTIVE: To investigate the safety and efficacy of LVIS Jr stent-assisted coiling (SAC) of intracranial aneurysms (IAs) in small-diameter parent arteries and determine the factors influencing incomplete aneurysm occlusion. MATERIAL AND METHODS: Clinical and imaging data of 130 patients with IAs in small-diameter parent arteries that were treated with LVIS Jr SAC were retrospectively analyzed. Stent apposition was evaluated by high-resolution flat detector CT, and aneurysm embolization density was evaluated using 2D-DSA. Perioperative complications were recorded. Multivariate logistic regression analyses were performed to determine possible factors for incomplete aneurysm occlusion. RESULTS: In this study, 130 patients (60 and 70 patients with ruptured and unruptured aneurysms, respectively) were successfully treated with LVIS Jr SAC. Immediate digital subtraction angiography (DSA) showed that the aneurysm occlusion was Raymond-Roy class I, II, IIIa, and IIIb in 93 (71.5%), 24 (18.5%), 8 (6.2%), and 5 (3.8%) cases, respectively. There were three cases of acute in-stent thrombosis and two cases of severe vasospasm observed during the perioperative period. The 6­month follow-up angiograms indicated that complete aneurysm occlusion in 122 patients was 79.5% (97/122). Multivariate logistic regression analyses showed that an aneurysm size > 10.0 mm, parent artery mean diameter < 2.0 mm, and incomplete stent apposition at the aneurysm neck were possible risk factors for incomplete aneurysm occlusion. CONCLUSION: The LVIS Jr SAC is effective for managing IAs in small-diameter parent arteries. An aneurysm size > 10.0 mm, parent artery mean diameter < 2.0 mm, and incomplete stent apposition at the aneurysm neck are possible risk factors for incomplete aneurysm occlusion.

High-throughput sequencing reveals differences in microbial community structure and diversity in the conjunctival tissue of healthy and type 2 diabetic mice.

BACKGROUND: To investigate the differences in bacterial and fungal community structure and diversity in conjunctival tissue of healthy and diabetic mice. METHODS: RNA-seq assays and high-throughput sequencing of bacterial 16 S rDNA and fungal internal transcribed spacer (ITS) gene sequences were used to identify differentially expressed host genes and fungal composition profiles in conjunctival tissues of diabetic BKS-db/db mice and BKS (control) mice. Functional enrichment analysis of differentially expressed genes and the correlation between the relative abundance of bacterial and fungal taxa in the intestinal mucosa were also performed. RESULTS: Totally, 449 differential up-regulated genes and 1,006 down-regulated genes were identified in the conjunctival tissues of diabetic mice. The differentially expressed genes were mainly enriched in metabolism-related functions and pathways. A decrease in conjunctival bacterial species diversity and abundance in diabetic mice compared to control mice. In contrast, fungal species richness and diversity were not affected by diabetes. The microbial colonies were mainly associated with cellular process pathways regulating carbohydrate and lipid metabolism, as well as cell growth and death. Additionally, some interactions between bacteria and fungi at different taxonomic levels were also observed. CONCLUSION: The present study revealed significant differences in the abundance and composition of bacterial and fungal communities in the conjunctival tissue of diabetic mice compared to control mice. The study also highlighted interactions between bacteria and fungi at different taxonomic levels. These findings may have implications for the diagnosis and treatment of diabetes.

[Determination of four phenolic endocrine-disrupting chemicals in water by dispersive solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry based on metal-organic skeleton porous carbon materials].

Phenolic endocrine-disrupting chemicals (EDCs) are exogenous substances that interfere with the endocrine system and disrupt normal cell functions upon entering a living organism, leading to reproductive and developmental toxicity. Therefore, the development of a rapid and efficient analytical method for detecting phenolic EDCs in environmental waters is crucial. Owing to the low concentration of phenolic EDCs in environmental water, appropriate sample pretreatment methods are necessary to remove interferences caused by the sample matrix and enrich the target analytes before instrumental analysis. Dispersive solid-phase extraction (DSPE) has gained considerable attention as a simple and rapid sample pretreatment method for environmental-sample analysis. In this method, an adsorbent material is uniformly dispersed in a sample solution and the target analytes are extracted through processes such as vortexing. Compared with traditional solid-phase extraction (SPE), DSPE increases the contact area between the adsorbent and sample solution, reduces the required amounts of adsorbent and organic solvents, and improves the extraction efficiency. The adsorbent material plays a critical role in DSPE because it determines the extraction efficiency of the method. Metal-organic frameworks (MOFs) are porous framework materials composed of metal clusters and multifunctional organic ligands. They possess many excellent properties such as tunable pore sizes, large surface areas, and good thermal and chemical stability, rendering them ideal adsorbent materials for sample pretreatment. MOF-derived porous carbon materials obtained through high-temperature carbonization not only increase the density of MOF materials for better separation but also retain the advantages of a large surface area, highly ordered porous structure, and high porosity. In this study, a porous carbon material derived from an MOF, named as University of Oslo-66-carbon (UiO-66-C), was synthesized using a solvothermal method and applied as an adsorbent to enrich four phenolic EDCs (bisphenol A, 4-tert-octylphenol, 4-nonylphenol, and nonylphenol) in water. A method combining DSPE with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to analyze these phenolic EDCs in water. The UiO-66-C dosage, pH of water sample, adsorption time, eluent type and volume, elution time, and ion strength were optimized. Gradient elution was performed using methanol-water as the mobile phase. The target analytes were separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and multiple reaction monitoring (MRM) was conducted in negative electrospray ionization mode. The method exhibited a linear correlation within the range of 0.5-100 µg/L for the four phenolic EDCs. The limits of detection (LODs) and quantification (LOQs) of the four phenolic EDCs were 0.01-0.13 µg/L and 0.03-0.42 µg/L, respectively. The precision of the method was evaluated through intra- and inter-day relative standard deviations (RSDs), with values ranging from 1.5% to 10.6% and from 6.1% to 13.2%, respectively. When applied to the detection of phenolic EDCs in tap and surface water, the spiked recoveries of the four phenolic EDCs were 77.1%-116.6%. Trace levels of 4-nonylphenol and nonylphenol were detected in surface water at levels of 1.38 and 0.26 µg/L, respectively. The proposed method exhibits good accuracy and precision; thus, it provides a new rapid, efficient, and sensitive approach for the detection of phenolic EDCs in environmental water.

Fast real-time monitoring of meat freshness based on fluorescent sensing array and deep learning: From development to deployment.

A fluorescent sensor array (FSA) combined with deep learning (DL) techniques was developed for meat freshness real-time monitoring from development to deployment. The array was made up of copper metal nanoclusters (CuNCs) and fluorescent dyes, having a good ability in the quantitative and qualitative detection of ammonia, dimethylamine, and trimethylamine gases with a low limit of detection (as low as 131.56 ppb) in range of 5 âˆ¼ 1000 ppm and visually monitoring the freshness of various meats stored at 4 °C. Moreover, SqueezeNet was applied to automatically identify the fresh level of meat based on FSA images with high accuracy (98.17 %) and further deployed in various production environments such as personal computers, mobile devices, and websites by using open neural network exchange (ONNX) technique. The entire meat freshness recognition process only takes 5 âˆ¼ 7 s. Furthermore, gradient-weighted class activation mapping (Grad-CAM) and uniform manifold approximation and projection (UMAP) explanatory algorithms were used to improve the interpretability and transparency of SqueezeNet. Thus, this study shows a new idea for FSA assisted with DL in meat freshness intelligent monitoring from development to deployment.

Correlation between PD-1 and sPD-L1 expression levels in peripheral blood of DLBCL patients and their clinicopathological characteristics.

Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hans's classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hans's classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.

Favorable response to PD-1 inhibitor plus chemotherapy as first-line treatment for metastatic gastric mixed neuroendocrine-non-neuroendocrine tumor: a case report.

Gastric mixed neuroendocrine-non-neuroendocrine tumor (MiNEN), a rare malignancy, currently has no standard treatment. Here, we report a patient with pathologically confirmed gastric MiNEN following radical surgery with rapid postoperative distant tumor recurrence. Immunofluorescence results suggested intensive lymphocyte infiltration in the tumor. The programmed death receptor ligand 1 (PD-L1) immunohistochemistry 22C3 pharmDx assay showed tumor proportion score was 5% and combined positive score was 10. After 6 cycles of treatment with etoposide and cisplatin in combination with toripalimab, efficacy was assessed as a complete response. Our report shows that for gastric MiNEN patients with high expression of PD-L1, chemotherapy combined with immune checkpoint inhibitors may achieve more significant efficacy.

Tailoring Magnetism of Graphene Nanoflakes via Tip-Controlled Dehydrogenation.

Atomically precise graphene nanoflakes called nanographenes have emerged as a promising platform to realize carbon magnetism. Their ground state spin configuration can be anticipated by Ovchinnikov-Lieb rules based on the mismatch of π electrons from two sublattices. While rational geometrical design achieves specific spin configurations, further direct control over the π electrons offers a desirable extension for efficient spin manipulations and potential quantum device operations. To this end, we apply a site-specific dehydrogenation using a scanning tunneling microscope tip to nanographenes deposited on a Au(111) substrate, which shows the capability of precisely tailoring the underlying π-electron system and therefore efficiently manipulating their magnetism. Through first-principles calculations and tight-binding mean-field-Hubbard modeling, we demonstrate that the dehydrogenation-induced Au-C bond formation along with the resulting hybridization between frontier π orbitals and Au substrate states effectively eliminate the unpaired π electron. Our results establish an efficient technique for controlling the magnetism of nanographenes.