PG I and PG II show unique value in diagnosing postoperative biochemical recurrence in patients with gastric cancer after total gastrectomy.

OBJECTIVE: To investigate the potential of group I pepsinogen (PG I) and group II pepsinogen (PG II) as diagnostic markers for recurrence in gastric cancer (GC) patients post-total gastrectomy. METHODS: Ninety-six patients who underwent total gastrectomy for GC between June 2022 and June 2023 were included in this study. Clinical data, serum samples, and ascites samples were collected. Patients were categorized based on recurrence status at the time of sample collection and the primary tumor site. PG I and PG II levels were determined using a chemiluminescent immunoassay, and their clinical utility following total gastrectomy for GC was evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: This study included 96 GC patients who underwent total gastrectomy, 55 of whom experienced postoperative recurrence (57.29%). The levels of serum PG I (27.86 (27.04, 30.97) vs. 26.05 (24.16, 27.09) ng/mL; P < 0.0001) and PG II (1.95 (1.23, 3.05) vs. 0.63 (0.47, 0.90) ng/mL; P < 0.0001) were significantly greater in the recurrent group compared to the non-recurrent group. The secretion of PG I and/or PG II by metastatic cancer cells correlated with the primary lesion site. When the cut-off value for serum PG I was 26.93 ng/mL, the area under the curve (AUC) for PG I was 0.77. When the cut-off value for serum PG II was 0.96 ng/mL, the AUC reached 0.90. The combined AUC was 0.97. CONCLUSION: These findings suggest that serum PG I and PG II are valuable biomarkers for identifying GC patients with biochemical recurrence post-total gastrectomy.

An On-Treatment Decreased Trend of Serum IL-6 and IL-8 as Predictive Markers Quickly Reflects Short-Term Efficacy of PD-1 Blockade Immunochemotherapy in Patients with Advanced Gastric Cancer.

Objective: Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. Materials and Methods: The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-α, IL-1ß, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results: When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1ß, IL-2R, IL-10, IL-17, and TNF-α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. Conclusion: Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy.

Chronic Stress Exacerbates the Immunosuppressive Microenvironment and Progression of Gliomas by Reducing Secretion of CCL3.

As understanding of cancer has deepened, increasing attention has been turned to the roles of psychological factors, especially chronic stress-induced depression, in the occurrence and development of tumors. However, whether and how depression affects the progression of gliomas are still unclear. In this study, we have revealed that chronic stress inhibited the recruitment of tumor-associated macrophages (TAM) and other immune cells, especially M1-type TAMs and CD8+ T cells, and decreased the level of proinflammatory cytokines in gliomas, leading to an immunosuppressive microenvironment and glioma progression. Mechanistically, by promoting the secretion of stress hormones, chronic stress inhibited the secretion of the chemokine CCL3 and the recruitment of M1-type TAMs in gliomas. Intratumoral administration of CCL3 reprogrammed the immune microenvironment of gliomas and abolished the progression of gliomas induced by chronic stress. Moreover, levels of CCL3 and M1-type TAMs were decreased in the tumor tissues of glioma patients with depression, and CCL3 administration enhanced the antitumor effect of anti-PD-1 therapy in orthotopic models of gliomas undergoing chronic stress. In conclusion, our study has revealed that chronic stress exacerbates the immunosuppressive microenvironment and progression of gliomas by reducing the secretion of CCL3. CCL3 alone or in combination with an anti-PD-1 may be an effective immunotherapy for the treatment of gliomas with depression. See related Spotlight by Cui and Kang, p. 514.

Phase separation-mediated biomolecular condensates and their relationship to tumor.

Phase separation is a cellular phenomenon where macromolecules aggregate or segregate, giving rise to biomolecular condensates resembling "droplets" and forming distinct, membrane-free compartments. This process is pervasive in biological cells, contributing to various essential cellular functions. However, when phase separation goes awry, leading to abnormal molecular aggregation, it can become a driving factor in the development of diseases, including tumor. Recent investigations have unveiled the intricate connection between dysregulated phase separation and tumor pathogenesis, highlighting its potential as a novel therapeutic target. This article provides an overview of recent phase separation research, with a particular emphasis on its role in tumor, its therapeutic implications, and outlines avenues for further exploration in this intriguing field.

Ultra-thin 2D bimetallic MOF nanosheets for highly sensitive and stable detection of glucose in sweat for dancer.

The measurement of glucose concentration in sweat is expected to replace the existing blood glucose detection, which realize the effective way of non-invasive monitoring of human glucose concentration in dancing. High precision glucose detection can be achieved by adjusting the electrode material of the sensor. Thus, in this work, the bimetallic organic frameworks (bi-MOFs) materials containing Mn and Ni ions (NiMn-MOF) with ultrathin nanosheets have been exquisitely designed. The ultrathin nanosheet and heterogeneous metal ions in the structure optimize the electronic structure, which improves the electrical conductivity of MOFs. The success of the preparation strategy leads the good electrocatalytic performance of NiMn-MOF for glucose detection. Detailedly, NiMn-MOF shows high sensitivity of 1576 µA mM-1 cm-2 in the linear range from 0 to 0.205 mM and the wide linear region of 0.255-2.655 mM and 3.655-5.655 mM were also observed. In addition, the high repeatability, reproductivity, long-term stability and ultra-low limited of detection (LOD, 0.28 µM, S/N = 3) provide foundation for the practical sensor application of this NiMn-MOF nanosheets. Remarkably, as designed NiMn-MOF sensor can accurately measure glucose in sweat showing great potential in the field of wearable glucose monitoring during dancing.

Towards Sustainable Green Adjuvants for Microbial Pesticides: Recent Progress, Upcoming Challenges, and Future Perspectives.

Microbial pesticides can be significantly improved by adjuvants. At present, microbial pesticide formulations are mainly wettable powders and suspension concentrations, which are usually produced with adjuvants such as surfactants, carriers, protective agents, and nutritional adjuvants. Surfactants can improve the tension between liquid pesticides and crop surfaces, resulting in stronger permeability and wettability of the formulations. Carriers are inert components of loaded or diluted pesticides, which can control the release of active components at appropriate times. Protective agents are able to help microorganisms to resist in adverse environments. Nutritional adjuvants are used to provide nutrients for microorganisms in microbial pesticides. Most of the adjuvants used in microbial pesticides still refer to those of chemical pesticides. However, some adjuvants may have harmful effects on non-target organisms and ecological environments. Herein, in order to promote research and improvement of microbial pesticides, the types of microbial pesticide formulations were briefly reviewed, and research progress of adjuvants and their applications in microbial pesticides were highlighted, the challenges and the future perspectives towards sustainable green adjuvants of microbial pesticides were also discussed in this review.

Moderated by personal perception: The preventive relationship between home HIIT dance and depression during the COVID-19 pandemic in China.

Introduction: Lockdowns during the COVID-19 pandemic were believed to greatly increase the risk of depression among isolated residents in both China and in Western countries. How to effectively reduce this risk has become one of the key issues in the field of public mental health. Methods: The present study seeks to examine the preventive relationship between doing home HIIT dance-which became popular during Shanghai's COVID-19 lockdown in 2022-and depression, and how such a preventive relationship has been mediated by different personal perception factors using an online survey with 528 samples. Results: The preventive relationship between doing home HIIT dance and depression was differently mediated by residents' personal perception factors, such as perceived benefits, severity, and self-efficacy, based on the health belief model. Discussion: These results deepen the research on the psychological effects of doing home HIIT dance on preventing depression, especially in the COVID-19 lockdown period, emphasizing the possible moderation effects of different self-perception factors.

Sandwich Biomimetic Scaffold Based Tendon Stem/Progenitor Cell Alignment in a 3D Microenvironment for Functional Tendon Regeneration.

Tendon injuries are some of the most commonly diagnosed musculoskeletal diseases. Tendon regeneration is sensitive to the topology of the substitute as it affects the cellular microenvironment and homeostasis. To bionic in vivo three-dimensional (3D) aligned microenvironment, an ordered 3D sandwich model was used to investigate the cell response in the tendon. First, high-resolution 3D printing provided parallel-grooved topographical cues on the hydrogel surface. Then the cells were seeded on its surface to acquire a 2D model. Afterward, an additional hydrogel coating layer was applied to the cells to create the 3D model. The interaction between cells and order structures in three-dimensions is yet to be explored. The study found that the tendon stem/progenitor cells (TSPCs) still maintain their ordering growth in the 3D model as in the 2D model. The study also found that the 3D-aligned TSPCs exhibited enhanced tenogenic differentiation through the PI3K-AKT signaling pathway and presented a less inflammatory phenotype than those in the 2D model. The in vivo implantation of such a 3D-aligned TSPC composite promoted tendon regeneration and mitigated heterotopic ossification in an Achilles defect model. These findings demonstrated that 3D-aligned TSPCs within a biomimetic topology environment are promising for functional tendon regeneration.

The impact of COVID-19 on the employment status and psychological expectations of college graduates: Empirical evidence from the survey data of Chinese recruitment websites.

Based on the big data and survey data of online recruitment platform, this paper empirically tests the impact of COVID-19 on the employment status and psychological expectations of college graduates. The results show that: under the impact of COVID-19 epidemic, both supply and demand sides of college graduates' employment market are affected, such as the decline of recruitment demand, the rise of the employment supply, and the obvious decrease of employment market prosperity. The impacts of COVID-19 epidemic on college graduates' employment status and psychological expectation in different cities are heterogeneous. In the short term, the epidemic has a negative impact on the employment of graduates, but the employment situation is gradually improving with the support of national policies. Under the influence of COVID-19 epidemic, graduates will change their employment location and expected salary, and they tend to choose "temporary non-employment," and their proportions of getting offers and signing contracts are significantly reduced. This paper suggests: Firstly, we should continue to push forward the action plan of "expanding jobs in graduation season to promote employment," and strengthen the persistence and permanence of employment promotion policies for college graduates; Secondly, encourage college students to change their employment concept and rationally adjust their employment expectations; Thirdly, to promote the development of flexible employment of college graduates, it is necessary to strengthen the propaganda of flexible employment, so that students can understand relevant policies; Fourthly, strengthen employment guidance services for graduates from poor families to ensure the continuity and stability of employment assistance policies.

Does Internet Entertainment Reduce the Cognitive Ability of Children? Evidence from the China Education Panel Survey.

Internet technology has been assimilated into children's educational system on an in-depth level. In particular, the number of children who use the internet for entertainment has been rapidly increasing. However, there has been a debate as to whether internet entertainment can have a detrimental impact on children's cognitive ability. This paper investigates the effect of internet entertainment on the cognitive ability of children in the Chinese context. The results show no evidence of associations between internet entertainment and children's cognitive ability. However, the additional analysis provides preliminary evidence suggesting that internet entertainment can be beneficial to children who use it for entertainment only on weekends but detrimental for those who spend leisure time online daily. In addition, the findings are robust in a variety of sensitivity tests. We also examine whether the effects of internet entertainment on children's cognitive ability in different family environments are heterogeneous. The findings suggest that parents' internet habits, parents' internet supervision, parental relationship, family education and living area play a moderating role in the relationship between internet entertainment and children's cognitive ability. This study offers useful insights into the current global debate on the nexus between internet entertainment and children's cognitive ability and also provides suggestions for parents, children, regulators and policymakers.

SU4312 Represses Glioma Progression by Inhibiting YAP and Inducing Sensitization to the Effect of Temozolomide.

SU4312, initially designed as a multi-target tyrosine kinase inhibitor, is consequently reported to inhibit tumor angiogenesis by blocking VEGFR. However, although SU4312 can penetrate the brain-blood barrier, its potential to inhibit glioma growth is unknown. In this study, we report that SU4312 inhibited glioma cell proliferation and down-regulated yes-associated protein (YAP), the key effector of the hippo pathway. The exogenous over-expression of YAP partially restored the inhibitory effect of SU4312 on glioma progression. Interestingly, SU4312 sensitized the antitumor effect of temozolomide, both in vitro and in vivo. Moreover, SU4312 decreased the M2tumor-associated macrophages and enhanced anti-tumor immunity by down-regulating the YAP-CCL2 axis. In conclusion, our results suggest that SU4312 represses glioma progression by down-regulating YAP transcription and consequently CCL2 secretion. SU4312 may be synergistic with temozolomide for glioma treatment.

Deep Learning-Based Automated Detection of Arterial Vessel Wall and Plaque on Magnetic Resonance Vessel Wall Images.

Purpose: To develop and evaluate an automatic segmentation method of arterial vessel walls and plaques, which is beneficial for facilitating the arterial morphological quantification in magnetic resonance vessel wall imaging (MRVWI). Methods: MRVWI images acquired from 124 patients with atherosclerotic plaques were included. A convolutional neural network-based deep learning model, namely VWISegNet, was used to extract the features from MRVWI images and calculate the category of each pixel to facilitate the segmentation of vessel wall. Two-dimensional (2D) cross-sectional slices reconstructed from all plaques and 7 main arterial segments of 115 patients were used to build and optimize the deep learning model. The model performance was evaluated on the remaining nine-patient test set using the Dice similarity coefficient (DSC) and average surface distance (ASD). Results: The proposed automatic segmentation method demonstrated satisfactory agreement with the manual method, with DSCs of 93.8% for lumen contours and 86.0% for outer wall contours, which were higher than those obtained from the traditional U-Net, Attention U-Net, and Inception U-Net on the same nine-subject test set. And all the ASD values were less than 0.198 mm. The Bland-Altman plots and scatter plots also showed that there was a good agreement between the methods. All intraclass correlation coefficient values between the automatic method and manual method were greater than 0.780, and greater than that between two manual reads. Conclusion: The proposed deep learning-based automatic segmentation method achieved good consistency with the manual methods in the segmentation of arterial vessel wall and plaque and is even more accurate than manual results, hence improved the convenience of arterial morphological quantification.

FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1.

BACKGROUND: We previously report that yes-associated protein (YAP), the core downstream effector of Hippo pathway, promotes the malignant progression of glioblastoma (GBM). However, although classical regulatory mechanisms of YAP are well explored, how YAP is modulated by the Hippo-independent manner remains poorly understood. Meanwhile, the nonreceptor tyrosine kinase Fyn-related kinase (FRK), which exhibits low expression and possesses tumor suppressor effects in GBM, is reported to be involved in regulation of protein phosphorylation. Here, we examined whether FRK could impede tumor progression by modulating YAP activities. METHODS: Human GBM cells and intracranial GBM model were used to assess the effects of FRK and YAP on the malignant biological behaviors of GBM. Immunoblotting and immunohistochemistry were used to detect the expression of core proteins in GBM tissues. Co-immunoprecipitation, proximity ligation assay, luciferase assay and ubiquitination assay were utilized to determine the protein-protein interactions and related molecular mechanisms. RESULTS: The expression levels of FRK and YAP were inversely correlated with each other in glioma tissues. In addition, FRK promoted the ubiquitination and degradation of YAP, leading to tumor suppression in vitro and in vivo. Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP. Siah1 is required for YAP destabilization initiated by FRK. CONCLUSIONS: We identify a novel mechanism by which FRK orchestrates tumor-suppression effect through phosphorylating YAP and inducing its ubiquitination by Siah1. FRK-Siah1-YAP signaling axis may serve as a potential therapeutic target for GBM treatment.

Entrepreneurial Capability, Career Development, and Entrepreneurial Intention: Evidence From China's HR Survey Data.

Based on 2018 China's Human Resource Employees Survey Data, this study uses the probit model to examine the impact of entrepreneurial ability and career development on HR's entrepreneurial intention. In terms of entrepreneurial ability, the results show that the educational background of Human Resource Management, cross-disciplinary knowledge, job-hopping experience, and the number of subordinates have significant positive impacts on HR's entrepreneurial intention. In terms of career development, lack of promotion space, skill upgrading opportunities, and lower than expected income have significant positive impacts on HR's entrepreneurial intention, and these impacts are heterogeneous among different enterprises. This study suggests that potential entrepreneurs can be identified from the explicit characteristics, which reflect HR's entrepreneurial abilities, and it is necessary to face up to the influence of career development on HR's entrepreneurial intention and encourage them to participate in on-the-job entrepreneurship. This study suggests that HR's entrepreneurial ability should be regarded as an important starting point for entrepreneurial success, and it is necessary to improve HR's career development system to create more opportunities for on-the-job entrepreneurship, and government should implement differentiated and precise entrepreneurial support policies to encourage HR's entrepreneurship.

Point-of-Care Technologies for the Advancement of Precision Medicine in Heart, Lung, Blood, and Sleep Disorders.

The commercialization of new point of care technologies holds great potential in facilitating and advancing precision medicine in heart, lung, blood, and sleep (HLBS) disorders. The delivery of individually tailored health care to a patient depends on how well that patient's health condition can be interrogated and monitored. Point of care technologies may enable access to rapid and cost-effective interrogation of a patient's health condition in near real time. Currently, physiological data are largely limited to single-time-point collection at the hospital or clinic, whereas critical information on some conditions must be collected in the home, when symptoms occur, or at regular intervals over time. A variety of HLBS disorders are highly dependent on transient variables, such as patient activity level, environment, time of day, and so on. Consequently, the National Heart Lung and Blood Institute sponsored a request for applications to support the development and commercialization of novel point-of-care technologies through small businesses (RFA-HL-14-011 and RFA-HL-14-017). Three of the supported research projects are described to highlight particular point-of-care needs for HLBS disorders and the breadth of emerging technologies. While significant obstacles remain to the commercialization of such technologies, these advancements will be required to achieve precision medicine.

Semiconductor Electronic Label-Free Assay for Predictive Toxicology.

While animal experimentations have spearheaded numerous breakthroughs in biomedicine, they also have spawned many logistical concerns in providing toxicity screening for copious new materials. Their prioritization is premised on performing cellular-level screening in vitro. Among the screening assays, secretomic assay with high sensitivity, analytical throughput, and simplicity is of prime importance. Here, we build on the over 3-decade-long progress on transistor biosensing and develop the holistic assay platform and procedure called semiconductor electronic label-free assay (SELFA). We demonstrate that SELFA, which incorporates an amplifying nanowire field-effect transistor biosensor, is able to offer superior sensitivity, similar selectivity, and shorter turnaround time compared to standard enzyme-linked immunosorbent assay (ELISA). We deploy SELFA secretomics to predict the inflammatory potential of eleven engineered nanomaterials in vitro, and validate the results with confocal microscopy in vitro and confirmatory animal experiment in vivo. This work provides a foundation for high-sensitivity label-free assay utility in predictive toxicology.

Self-Locking Optoelectronic Tweezers for Single-Cell and Microparticle Manipulation across a Large Area in High Conductivity Media.

Optoelectronic tweezers (OET) has advanced within the past decade to become a promising tool for cell and microparticle manipulation. Its incompatibility with high conductivity media and limited throughput remain two major technical challenges. Here a novel manipulation concept and corresponding platform called Self-Locking Optoelectronic Tweezers (SLOT) are proposed and demonstrated to tackle these challenges concurrently. The SLOT platform comprises a periodic array of optically tunable phototransistor traps above which randomly dispersed single cells and microparticles are self-aligned to and retained without light illumination. Light beam illumination on a phototransistor turns off the trap and releases the trapped cell, which is then transported downstream via a background flow. The cell trapping and releasing functions in SLOT are decoupled, which is a unique feature that enables SLOT's stepper-mode function to overcome the small field-of-view issue that all prior OET technologies encountered in manipulation with single-cell resolution across a large area. Massively parallel trapping of more than 100,000 microparticles has been demonstrated in high conductivity media. Even larger scale trapping and manipulation can be achieved by linearly scaling up the number of phototransistors and device area. Cells after manipulation on the SLOT platform maintain high cell viability and normal multi-day divisibility.

γδ Τ cells enhance B cells for antibody production in Hashimoto's thyroiditis, and retinoic acid induces apoptosis of the γδ Τ cell.

TCR γδ(+) Τ cells are important in the pathogenesis of inflammatory and autoimmune conditions. This study investigated the effect of γδ T cells on autoantibody production in patients with Hashimoto's thyroiditis (HT). A total of 148 subjects were enrolled, including 99 patients with HT, 5 with simple goiters, and 44 healthy controls. Peripheral blood and thyroid mononuclear cells were subjected to flow cytometric analysis. Thyroid tissues underwent immunofluorescent staining and immunohistochemistry for γδ T cells and anti-thyroid antibody detection. Antibody production was measured by ELISA and automated chemiluminescent immunoassays. And activation and apoptosis of peripheral blood γδT cells and B cells were measured by flow cytometric analysis. The percentage of γδ T cells were greater in thyroid tissue from HT patients than that of goiter patients (n = 5, 5.33 ± 1.20 vs. 2.07 ± 0.44 %; P < 0.05), with the Vδ1(+) γδ T cell subset especially dominant. Frequencies of CD69 (8.42 ± 1.08 vs. 1.60 ± 0.38 %, P < 0.001), HLA-DR (58.12 ± 6.36 vs. 37.82 ± 3.70 %, P < 0.05), CD40L (1.58 ± 0.35 vs. 0.15 ± 0.05 %, P < 0.01), and ICOS (2.78 ± 0.66 vs. 0.28 ± 0.13 %, P < 0.01) expressed on γδ T cells from HT patients (n = 19) were significantly increased compared with those of healthy controls (n = 15). More importantly, γδ T cells from HT patients enhanced B cells for antibody production, and all-trans retinoic acid (ATRA) treatment inhibited the effect by inducing apoptosis of γδ Τ cells. γδ Τ cells appear to play an important role in the pathogenesis of HT, and ATRA might be an effective regulator for HT patients.