One size might fit all: Indole-3-propionic acid potentiates pan-cancer immunotherapy.

Microbial-based therapies have the potential to combat immunotherapy resistance, extending the boundaries of oncological therapeutics. In a recent issue of Cell, Jia et al. demonstrates an example of microbial collaboration to produce a postbiotic that promotes the stemness program of CD8+ T cells to augment immunotherapy at the pan-cancer level.

Alterations in the immune landscape characterized by inflammatory activation and immune escape within 12 h after trauma.

BACKGROUND: Trauma is statistically a significant cause of mortality among patients across countries. Nevertheless, the precise correlation between genetic diagnostic markers and the intricate mechanism of trauma remains indistinct. METHODS: Our study exclusively centered on trauma patients and selected three trauma-related datasets from the Gene Expression Omnibus (GEO) database, all of which had blood samples collected within post-traumatic 12 h. Differential gene screening, the WGCNA and Cytoscape software were employed to analyze the two datasets, with a particular emphasis on the top 100 genes selected based on MCC algorithm scores. A logistic diagnostic model was constructed by analyzing the intersection genes in the third dataset, leading to the identification of diagnostic biomarkers with high efficiency. The global immune landscape of these patients was extensively investigated using a multidimensional approach. Meanwhile, the underlying pathological and physiological mechanisms associated with early trauma status are summarized by integrating existing literature. RESULTS: Out of these two GEO datasets, 21 overlapping genes were identified and incorporated into in the logistic diagnostic model constructed in the GSE36809 dataset. A panel of 9 genes was uncovered as a diagnostic biomarker, and their expression and correlation were subsequently verified. Additionally, by virtue of various algorithms, the findings revealed an upregulation of neutrophil expression and a downregulation of CD8+ T cell expression, indicating characteristic early trauma-induced inflammation activation and immune suppression. The correlation observed between the feature genes and immune cells serves to validate the exceptional diagnostic capability of these 9 genes in identifying trauma status and their promising potential for patients who could benefit from targeted immune interventions. Drawing from these findings, the discussion section offers insights into the underlying pathological and physiological mechanisms at play. CONCLUSION: Our research has discovered a novel diagnostic biomarker and unveiled its association with post-traumatic immune alterations. This breakthrough enables accurate and timely diagnosis of early trauma, facilitating the implementation of appropriate healthcare interventions.

Crosstalk between Exercise and Immunotherapy: Current Understanding and Future Directions.

Accumulated evidence highlights that exercise can modulate multiple cytokines, influencing transcriptional pathways, and reprogramming certain metabolic processes, ultimately promoting antitumor immunity and enhancing the efficacy of immune checkpoint inhibitors in cancer patients. Exploring the mechanisms behind this will, for one thing, help us uncover key factors and pathways in exercise-assisted cancer immunotherapy, offering more possibilities for future treatment methods. For another, it will support the development of more personalized and effective exercise prescriptions, thereby improving the prognosis of cancer patients.

Microbiome and lung cancer: carcinogenic mechanisms, early cancer diagnosis, and promising microbial therapies.

Microbiomes in the lung, gut, and oral cavity are correlated with lung cancer initiation and progression. While correlations have been preliminarily established in earlier studies, delving into microbe-mediated carcinogenic mechanisms will extend our understanding from correlation to causation. Building upon the causative relationships between microbiome and lung cancer, a novel concept of microbial biomarkers has emerged, mainly encompassing cancer-specific bacteria and circulating microbiome DNA. They might function as noninvasive liquid biopsy techniques for lung cancer early detection. Furthermore, potential microbial therapies have displayed initial efficacy in lung cancer treatment, providing multiple avenues for therapeutic intervention. Herein, we will discuss the molecular mechanisms and signaling pathways through which microbes influence lung cancer initiation and development. Additionally, we will summarize recent findings on microbial biomarkers as a member of tumor liquid biopsy techniques and provide an overview of the latest advances in various microbe-assisted/mediated therapeutic approaches for lung cancer.

Exploring the causal relationship between immune cells and idiopathic pulmonary fibrosis: a bi-directional Mendelian randomization study.

BACKGROUND: The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF. METHODS: By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells. To ensure the reliability of the results, combined sensitivity analyses and inverse Mendelian analyses were conducted. Moreover, within subgroups, multivariate Mendelian randomization analyses were utilized to investigate the autonomous causal connection between immune cell characteristics and IPF. RESULTS: After adjusting for false discovery rate, it was discovered that 20 immunophenotypes exhibited a significant association with IPF. After subgrouping for multivariate Mendelian randomization analysis, there were six immunophenotypes that remained significantly associated with IPF. These included CD33 + HLA DR + CD14dim (OR = 0.96, 95% CI 0.93-0.99, P = 0.033), HLA DR + NK (OR = 0.92, 95% CI 0.85-0.98, P = 0.017), CD39 + CD8 + T cell %T cell (OR = 0.93, 95% CI 0.88-0.99, P = 0.024), CD3 on activated & secreting Treg (OR = 0.91, 95% CI 0.84-0.98, P = 0.026), PDL-1 on CD14- CD16 + monocyte (OR = 0.89, 95% CI 0.84-0.95, P = 8 × 10-4), and CD45 on CD33 + HLA DR + CD14- (OR = 1.08, 95% CI 1.01-1.15, P = 0.011). CONCLUSION: Our study reveals a noteworthy association between IPF and various immune cells, providing valuable insights for clinical research and aiding the advancement of immunologically-based therapeutic strategies.

Into the era of mycobiome-driven cancer research.

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.

Cell-cell communication characteristics in breast cancer metastasis.

Breast cancer, a highly fatal disease due to its tendency to metastasize, is the most prevalent form of malignant tumors among women worldwide. Numerous studies indicate that breast cancer exhibits a unique predilection for metastasis to specific organs including the bone, liver, lung, and brain. However, different types of, The understanding of the heterogeneity of metastatic breast cancer has notably improved with the recent advances in high-throughput sequencing techniques. Focusing on the modification in the microenvironment of the metastatic organs and the crosstalk between tumor cells and in situ cells, noteworthy research points include the identification of two distinct modes of tumor growth in bone metastases, the influence of type II pneumocyte on lung metastases, the paradoxical role of Kupffer cells in liver metastases, and the breakthrough of the blood-brain barrier (BBB) breach in brain metastases. Overall, this review provides a comprehensive overview of the characteristics of breast cancer metastases, shedding light on the pivotal roles of immune and resident cells in the development of distinct metastatic foci.

The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study.

INTRODUCTION: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors. METHODS: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out. RESULTS: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results. CONCLUSION: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches.

Beyond probiotics: postbiotics sensitize cancer cells to immune checkpoint inhibitors.

Accumulated research corroborates the feasibility of microbial antitumor therapies, enriching the diversity of cancer therapeutics. Recently, Ferrari et al. revealed the role of postbiotics in sensitizing cancer cells to immune checkpoint inhibitors (ICIs) and synergizing immunotherapy. Particularly, phytosphingosine induces upstream MYD88/NF-κB and downstream NLRC5 activation, enhances T cell effector responses, and inhibits tumor growth.

Harnessing the power of traditional Chinese medicine monomers and compound prescriptions to boost cancer immunotherapy.

At present, cancer is the largest culprit that endangers human health. The current treatment options for cancer mainly include surgical resection, adjuvant radiotherapy and chemotherapy, but their therapeutic effects and long-term prognosis are unsatisfactory. Immunotherapy is an emerging therapy that has completely transformed the therapeutic landscape of advanced cancers, and has tried to occupy a place in the neoadjuvant therapy of resectable tumors. However, not all patients respond to immunotherapy due to the immunological and molecular features of the tumors. Traditional Chinese Medicine (TCM) provides a new perspective for cancer treatment and is considered to have the potential as promising anti-tumor drugs considering its immunoregulatory properties. This review concludes commonly used TCM monomers and compounds from the perspective of immune regulatory pathways, aiming to clearly introduce the basic mechanisms of TCM in boosting cancer immunotherapy and mechanisms of several common TCM. In addition, we also summarized closed and ongoing trials and presented prospects for future development. Due to the significant role of immunotherapy in the treatment of non-small cell lung cancer (NSCLC), TCM combined with immunotherapy should be emphasized in NSCLC.

Identification and validation of diagnostic biomarkers for intrahepatic cholestasis of pregnancy based on untargeted and targeted metabolomics analyses of urine metabolite profiles.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a prevalent pregnancy-specific complication that presents with maternal itching and elevated serum bile acid levels. ICP is associated with unfavorable pregnancy outcomes, severely decreasing the pregnant woman's quality of life. Timely identification of ICP is crucial for effective management and improved outcomes. METHODS: We collected urine samples from 8 patients with ICP and 8 healthy individuals. We used Liquid Chromatography-Mass Spectrometry (LC-MS) to detect metabolite expression levels, then conducted a series of bioinformatic analyses to explore the potential biological meanings of differentially expressed metabolites, and preliminarily discovered several candidate biomarkers. To validate these candidate biomarkers, we performed Gas Chromatography-Mass Spectrometry (GC-MS) detection and analyzed their diagnostic values using receiver operating characteristic (ROC) curve. RESULTS: Untargeted metabolomics data showed that 6129 positive peaks and 6218 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory capability in discriminating ICP specimens from controls. Subsequent analysis extracted 64 significantly differentially expressed metabolites, which could be potential biomarkers for diagnosis of ICP. Based on the KEGG enrichment analyses, six candidate biomarkers were preliminarily identified. Two most promising biomarkers (3-hydroxypropionic acid and uracil) were validated by targeted metabolomics analyses with the area under the curve (AUC) of 0.920 and 0.850 respectively. CONCLUSION: Based on preliminary screening from untargeted metabolomics and subsequent validation through targeted metabolomics, 3-hydroxypropionic acid and uracil were identified as promising diagnostic biomarkers for ICP.

Untangling the web of intratumor microbiota in lung cancer.

Microbes are pivotal in contemporary cancer research, influencing various biological behaviors in cancer. The previous notion that the lung was sterile has been destabilized by the discovery of microbiota in the lower airway and lung, even within tumor tissues. Advances of biotechnology enable the association between intratumor microbiota and lung cancer to be revealed. Nonetheless, the origin and tumorigenicity of intratumor microbiota in lung cancer still remain implicit. Additionally, accumulating evidence indicates that intratumor microbiota might serve as an emerging biomarker for cancer diagnosis, prognosis, and even a therapeutic target across multiple cancer types, including lung cancer. However, research on intratumor microbiota's role in lung cancer is still nascent and warrants more profound exploration. Herein, this paper provides an extensive review of recent advancements in the following fields, including 1) established and emerging biotechnologies utilized to study intratumor microbiota in lung cancer, 2) causation between intratumor microbiota and lung cancer from the perspectives of translocation, cancerogenesis and metastasis, 3) potential application of intratumor microbiota as a novel biomarker for lung cancer diagnosis and prognosis, and 4) promising lung cancer therapies via regulating intratumor microbiota. Moreover, this review addresses the limitations, challenges, and future prospects of studies focused on intratumor microbiota in lung cancer.

Identification and validation of a novel NK cells-related signature to predict prognosis and immune microenvironment in LUAD.

BACKGROUND: The prevalence and fatality rates of lung cancer are experiencing a rapid escalation. Natural Killer (NK) cells have been established to have a crucial role in both tumor initiation and progression. Nevertheless, uncertainties persist regarding their precise implications in the prognosis of LUAD. METHODS: The data were obtained from reputable sources, such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and our internally generated sequencing data. Utilizing the TCGA data as a background, we selected intersecting genes, validated by cluster analysis, to establish a Cox model and validated it using the GEO datasets. Furthermore, we conducted extensive analyses to investigate the significance of potential biomarkers in relation to immune cell infiltration, single-cell data, differential gene expression, and drug sensitivity. RESULTS: 67 immune-related genes associated with NK cells (NK-IRGs) were identified in the TCGA datasets, whose research potential was demonstrated by cluster analysis. A prognostic signature was identified utilizing the univariate and multivariate Cox model, resulting in the identification of five genes, which was validated using GEO datasets. Additionally, the nomogram's calibration curve demonstrated exceptional concordance between the projected and actual survival rates. Subsequent investigations uncovered that this prognostic signature demonstrated its independence as a risk factor. Notably, in the low-risk group, NK cells exhibited elevated levels of immune checkpoint molecules, indicating heightened sensitivity to immune therapy. These findings highlight the potential of utilizing this signature as a valuable tool in the selection of patients who could benefit from targeted immune interventions.

A comprehensive review of novel biomarkers in the diagnosis of intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a disease specific to pregnancy, featuring maternal itching and elevated serum bile acid levels. It leads to a series of adverse pregnancy outcomes as well as increased fetal mortality. Routine biochemical markers fail to fulfill the tremendous clinical requirements, thereby novel effective biomarkers are urgently desired. In our review, the potential novel biomarkers for ICP diagnosis are classified into four categories and elaborated in detail. The concrete diagnostic performances (sensitivity, specificity and area under the curve) of these biomarkers are demonstrated in tables. Moreover, the relationships between some biomarkers and ICP pathogenesis are briefly expounded. Nevertheless, only a few novel biomarkers are ideal, and their clinical applicability requires more evidence from larger multicenter trials.

Advances in the diagnosis and prognosis of minimal residual lesions of breast cancer.

PURPOSE: To review the latest research of minimal residual disease (MRD) in breast cancer as well as some emerging or potential detection methods for MRD in breast cancer. METHODS: Springer, Wiley, and PubMed databases were searched for the electronic literature with search terms of breast cancer, minimal residual disease, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, etc. RESULTS: Minimal residual disease refers to the occult micrometastasis or minimal residual lesions detected in patients with tumor after radical treatment. An early and dynamic monitoring of breast cancer MRD can contribute to clinical treatment decision-making, improving the diagnosis accuracy and prognosis of breast cancer patients. The updated knowledge regarding MRD in breast cancer diagnosis and prognosis were summarized, followed by the review of several emerging or potential detection technologies for MRD in breast cancer. With the developed new MRD detection technologies referring to CTCs, ctDNA and exosomes, the role of MRD in breast cancer has been growingly verified, which is expected to serve as a new risk stratification factor and prognostic indicator for breast cancer. CONCLUSION: This paper systematically reviews the research progress, opportunities and challenges in MRD in breast cancer in recent years.

Strong enhancement of Goos-Hänchen shift through the resonant optical tunneling effect.

The resonant optical tunneling effect (ROTE) originates from the frustrated total reflection effect because unique transmission characteristics are used to study high-sensitivity sensors. In this study, we theoretically demonstrated that choosing a suitable transmission gap made it possible for the ROTE structure based on hexagonal boron nitride and graphene to obtain a large Goos-Hänchen shift as high as tens of thousands of times the incident wavelength at a specific incident angle. The amplitude of the Goos-Hänchen shift was found to be sensitive to the central layer thickness but was also modulated by the tunneling gap on both sides. In addition, adjusting the chemical potential and relaxation time of the graphene sheets could alter the Goos-Hänchen shift. Our work provides a new way to explore the Goos-Hänchen effect and opens the possibility for the application of high-precision measurement technology based on the ROTE.

Communication wavelength investigation of bound states in the continuum of one-dimensional two-material periodic ring optical waveguide network.

In this study, a one-dimensional (1D) two-material period ring optical waveguide network (TMPROWN) was designed, and its optical properties were investigated. The key characteristics observed in the 1D TMPROWN include the following: (1) Bound states in continuum (BICs) can be generated in the optical waveguide network. (2) In contrast to the BICs previously reported in optical structures, the range of the BICs generated by the 1D TMPROWN is not only larger, but also continuous. This feature makes it possible for us to further study the electromagnetic wave characteristics in the range of the BICs. In addition, we analyzed the physical mechanisms of the BICs generated in the 1D TMPROWN. The 1D TMPROWN is simple in structure, demonstrates flexibility with respect to adjusting the frequency band of the BICs, and offers easy measurement of the amplitude and phase of electromagnetic waves. Hence, further research on high-power super luminescent diodes, optical switches, efficient photonic energy storage, and other optical devices based on the 1D TMPROWN designed in this study is likely to have implications in a broad range of applications.

A Bifunctional Silicon Dielectric Metasurface Based on Quasi-Bound States in the Continuum.

Quasi-bound states in the continuum provide an effective and observable way to improve metasurface performance, usually with an ultra-high-quality factor. Dielectric metasurfaces dependent on Mie resonances have the characteristic of significantly low loss, and the polarization can be affected by the parameter tuning of the structure. Based on the theory of quasi-bound states in the continuum, we propose and simulate a bifunctional resonant metasurface, whose periodic unit structure consists of four antiparallel and symmetrical amorphous silicon columns embedded in a poly(methyl methacrylate) layer. The metasurface can exhibit an extreme Huygens' regime in the case of an incident plane wave with linear polarization, while exhibiting chirality in the case of incident circular polarized light. Our structure provides ideas for promoting the multifunctional development of flat optical devices, as well as presenting potential in polarization-dependent fields.

Flexible Control of Two-Channel Transmission and Group Delay in an Optomechanical System with Double Quantum Dots Driven by External Field.

With the presence of a driving field applied to double quantum dots and a control field applied on the cavity, the transmission performance and group delay effect of a probe field have been theoretically studied in a hybrid optomechanical system (HOMS). Due to the interaction between the mechanical mode and the double quantum dots system, double optomechanically induced transparency (OMIT) arises in the HOMS. With the assistance of a driving field, the system can be tuned to switch on any one of the two OMIT windows, switch on both of the two OMIT windows or switch off both of the two OMIT windows by dynamically adjusting control of the optical field and the driving field. Furthermore, the transmitted probe fields of the two OMIT windows can be tuned to be absorbed or amplified with proper parameters of the driving field and control field. Moreover, the transmission properties of the two OMIT windows are asymmetrical. One can obtain the maximum group delay time of the probe field by optimizing the amplitude and phase of the driving field. These results provide a new way for constructing optically controlled nanostructured photonic switch and storage devices.