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The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights. This review underscores the multifaceted roles of GzmB, spanning immunological and pathological contexts, which call for further investigations to pave the way for innovative targeted therapies.

Beta-adrenergic receptor signaling regulates cellular processes associated with facilitating tumor cell proliferation and dampening anti-tumor immune response. These cellular processes may lead to compromised tumor control and cancer progression. Based on this ramification, Beta-blockers (BBs) have emerged as a potential treatment by inhibiting beta-adrenergic receptor signaling. This review aimed to investigate the relationship between the use of BBs and tumor progression and treatment response. Therefore, the authors explored several aspects: the potential synergistic relationship of BBs with chemotherapy and immunotherapy in enhancing the effectiveness of chemotherapeutic and immunotherapeutic treatments and their role in boosting endogenous immunity. Further, this review explores the distinctions between the major types of BBs: Non-selective Beta Blockers (NSBBs) and Selective Beta Blockers (SBBs), and their contributions to combinatory cancer treatment. In this review, we presented a perspective interpretation of research findings and future directions. Overall, this review discusses the potential and challenge that BBs present in improving the effectiveness and outcome of cancer treatment.

Treg play a central role in maintenance of self tolerance and homeostasis through suppression of self-reactive T cell populations. In addition to that role, Treg also survey cancers and suppress anti-tumor immune responses. Thus, understanding the unique attributes of Treg-tumor interactions may permit control of this pathologic suppression without interfering with homeostatic self-tolerance. This review will define the unique role of Treg in cancer growth, and the ways by which Treg inhibit a robust anti-tumor immune response. There will be specific focus placed on Treg homing to the tumor microenvironment (TME), TME formation of induced Treg (iTreg), mechanisms of suppression that underpin cancer immune escape, and trophic nonimmunologic effects of Treg on tumor cells.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic malignancies, and other hematologic and immunologic diseases. Donor-derived immune cells identify and attack cancer cells in the patient producing a unique graft-vs.-tumor (GVT) effect. This beneficial response renders allo-HCT one of the most effective forms of tumor immunotherapy. However, alloreactive donor T cells can damage normal host cells thereby causing graft-vs.-host disease (GVHD), which results in substantial morbidity and mortality. To date, GVHD remains as the major obstacle for more successful application of allo-HCT. Of special significance in this context are a number of cytotoxic pathways that are involved in GVHD and GVT response as well as donor cell engraftment. In this review, we summarize progress in the investigation of these cytotoxic pathways, including Fas/Fas ligand (FasL), perforin/granzyme, and cytokine pathways. Many studies have delineated their distinct operating mechanisms and how they are involved in the complex cellular interactions amongst donor, host, tumor, and infectious pathogens. Driven by progressing elucidation of their contributions in immune reconstitution and regulation, various interventional strategies targeting these pathways have entered translational stages with aims to improve the effectiveness of allo-HCT.

Immune checkpoint inhibitor therapies and allogeneic hematopoietic cell transplant (alloHCT) represent two distinct modalities that offer a chance for long-term cure in a diverse array of malignancies and have experienced many breakthroughs in recent years. Herein, we review the CD27-CD70 co-stimulatory pathway and its therapeutic potential in 1) combination with checkpoint inhibitor and other immune therapies and 2) its potential ability to serve as a novel approach in graft- versus -host disease (GVHD) prevention. We further review recent advances in the understanding of GVHD as a complex immune phenomenon between donor and host immune systems, particularly in the early stages with mixed chimerism, and potential novel therapeutic approaches to prevent the development of GVHD.

The use of tumor mutation-derived neoantigen represents a promising approach for cancer vaccines. Preclinical and early phase human clinical studies have shown the successful induction of tumor neoepitope-directed responses; however, overall clinical efficacy of neoantigen vaccines has been limited. One major obstacle of this strategy is the prevailing lack of sufficient understanding of the mechanism underlying the generation of neoantigen-specific CD8+ T cells. Here, we report a correlation between antitumor efficacy of neoantigen/toll-like receptor 3 (TLR3)/CD40 agonists vaccination and an increased frequency of circulating antigen-specific CD8+ T cells expressing CX3C chemokine receptor 1 (CX3CR1) in a preclinical model. Mechanistic studies using mixed bone marrow chimeras identified that CD40 and CD80/86, but not CD70 signaling in Batf3-dependent conventional type 1 dendritic cells (cDC1s) is required for the antitumor efficacy of neoantigen vaccine and generation of neoantigen-specific CX3CR1+ CD8+ T cells. Although CX3CR1+ CD8+ T cells exhibited robust in vitro effector function, in vivo depletion of this subset did not alter the antitumor efficacy of neoantigen/TLR3/CD40 agonists vaccination. These findings indicate that the vaccine-primed CX3CR1+ subset is dispensable for antitumor CD8+ T cell responses, but can be used as a blood-based T-cell biomarker for effective priming of CD8+ T cells as post-differentiated T cells. Taken together, our results reveal a critical role of CD40 and CD80/86 signaling in cDC1s in antitumor efficacy of neoantigen-based therapeutic vaccines, and implicate the potential utility of CX3CR1 as a circulating predictive T-cell biomarker in vaccine therapy.

Photocatalytic reduction is a promising approach to detoxifying carcinogenic Cr(VI) in water. Herein, CdS-sensitized Cs3PW12O40 composites were fabricated by electrostatic self-assembly followed by hydrothermal post-treatment strategy. The composite with 28.6 wt% CdS loading (CdS/CsPW) was characterized by XRD, FT-IR, SEM/TEM, EDX, UV-vis DRS, XPS, potentiometric titration, and N2 adsorption. The catalytic activity was evaluated by reducing Cr(VI) in the presence of EDTA under UV and visible light irradiation. The results revealed that CdS/CsPW had good photocatalytic reduction performance for Cr(VI) degradation under both UV and visible light illumination. After four-time repetitive use, ~ 93% of catalytic activity still remained. The photocatalytic reduction of Cr(VI) under visible light irradiation followed pseudo-first-order kinetics; the decreasing solution pH and initial Cr(VI) concentration, and increasing catalyst dosage and EDTA concentration were beneficial to Cr(VI) photoreduction. XPS analyses further indicated that the Cr(VI) adsorbed on surface of the catalyst was also reduced to Cr(III), and CdS and Cs3PW12O40 existed strong interaction. Meanwhile, the photoelectrons in CdS could migrate to Cs3PW12O40. Further, PL results verified CdS/CsPW heterostructure effectively suppressed the photogenerated electron-hole recombination. Based on experimental results, the mechanisms for Cr(VI) photoreduction by the prepared catalyst were proposed. This work may provide an attractive avenue to construct the efficient photocatalyst using polyoxometalates for environmental remediation.

Background Traditional detection methods face challenges in meeting the diverse clinical needs for diagnosing both lung cancer and infections within a single test. Onco-mNGS has emerged as a promising solution capable of accurately identifying infectious pathogens and tumors simultaneously. However, critical evidence is still lacking regarding its diagnostic performance in distinguishing between pulmonary infections, tumors, and non-infectious, non-tumor conditions in real clinical settings. Methods In this study, data were gathered from 223 participants presenting symptoms of lung infection or tumor who underwent Onco-mNGS testing. Patients were categorized into four groups based on clinical diagnoses: infection, tumor, tumor with infection, and non-infection-non-tumor. Comparisons were made across different groups, subtypes, and stages of lung cancer regarding copy number variation (CNV) patterns, microbiome compositions, and clinical detection indices. Results Compared to conventional infection testing methods, Onco-mNGS demonstrates superior infection detection performance, boasting a sensitivity of 81.82%, specificity of 72.55%, and an overall accuracy of 77.58%. In lung cancer diagnosis, Onco-mNGS showcases excellent diagnostic capabilities with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value reaching 88.46%, 100%, 91.41%, 100%, and 90.98%, respectively. In bronchoalveolar lavage fluid (BALF) samples, these values stand at 87.5%, 100%, 94.74%, 100%, and 91.67%, respectively. Notably, more abundant CNV mutation types and higher mutation rates were observed in adenocarcinoma (ADC) compared to squamous cell carcinoma (SCC). Concurrently, onco-mNGS data revealed specific enrichment of Capnocytophaga sputigeria in the ADC group and Candida parapsilosis in the SCC group. These species exhibited significant correlations with C reaction protein (CRP) and CA153 values. Furthermore, Haemophilus influenzae was enriched in the early-stage SCC group and significantly associated with CRP values. Conclusions Onco-mNGS has exhibited exceptional efficiencies in the detection and differentiation of infection and lung cancer. This study provides a novel technological option for achieving single-step precise and swift detection of lung cancer. Graphical Abstract

In this paper, a series of samples La0.7Sr0.3Mn1-xFexO3 (x = 0, 0.05, 0.10, 0.15, 0.2) were prepared. Among these samples, La0.7Sr0.3Mn0.85Fe0.15O3 showed better catalytic activity than the samples with undoped and other doped ones, so undoped iron La0.7Sr0.3MnO3 and doped iron La0.7Sr0.3Mn0.85Fe0.15O3 were characterized by X-ray diffraction (XRD), UV–Vis diffuse reflection analysis (UV–Vis DRS), vibrating sample magnetometer (VSM), transmission electron microscopy (TEM), scanning electron microscope (SEM), specific surface analysis (BET), and X-ray photoelectron spectroscopy (XPS). In addition, it takes methyl orange (MO) as the object of degradation, and the photocatalysis, Fenton-like reaction, and their synergistic catalytic effects as well as the catalytic mechanisms of La0.7Sr0.3Mn0.85Fe0.15O3 have been studied. The results show that La0.7Sr0.3Mn0.85Fe0.15O3 exhibits high solar-driven photocatalytic and Fenton-like catalytic activities for MO degradation. Moreover, there is an obvious synergistic catalytic effect of photocatalysis and Fenton-like catalytic activity. In addition, according to the free radical capture experiment, the hole, •OH and •O2− are the active substances in the synergistic catalytic process. The possible synergistic catalytic mechanism of La0.7Sr0.3Mn0.85Fe0.15O3 was also proposed. And the average pore size of the catalyst is 20.91 nm by BET. The near-superparamagnetic properties of La0.7Sr0.3Mn0.85Fe0.15O3 enable it to achieve simple separation in an external magnetic field, avoiding the disadvantages of ordinary catalysts that are difficult to separate. Therefore, La0.7Sr0.3Mn0.85Fe0.15O3 is an advanced multifunctional nanocatalyst and could be widely used in the field of wastewater treatment.The magnetic La0.7Sr0.3Mn0.85Fe0.15O3 was synthesized by hydrothermal method successfully, the photocatalysis, Fenton-like reaction and their synergistic catalytic effects as well as the catalytic mechanisms of La0.7Sr0.3Mn0.85Fe0.15O3 have been studied, It is not only a high efficient solar-driven photocatalyst, but also has Fenton -like catalytic properties, and both of them have synergistic catalytic effect. And those indicate that La0.7Sr0.3Mn0.85Fe0.15O3 is an advanced multi-functional catalyst.

Recently, the incidence of chlamydial pneumonia caused by rare pathogens such as or has shown a significant upward trend. The non-specific clinical manifestations and the limitations of traditional pathogen identification methods determine that chlamydial pneumonia is likely to be poorly diagnosed or even misdiagnosed, and may further result in delayed treatment or unnecessary antibiotic use. mNGS's non-preference and high sensitivity give us the opportunity to obtain more sensitive detection results than traditional methods for rare pathogens such as or . In the present study, we investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of pneumonia patients with different chlamydial infection patterns using mNGS. More co-infecting pathogens were found to be detectable in clinical samples from patients infected with compared to , suggesting that patients infected with may have a higher risk of mixed infection, which in turn leads to more severe clinical symptoms and a longer disease course cycle. Further, we also used mNGS data to analyze for the first time the characteristic differences in the lower respiratory tract microbiota of patients with and without chlamydial pneumonia, the impact of the pattern of infection on the lower respiratory tract microbiota, and the clinical relevance of these characteristics. Significantly different profiles of lower respiratory tract microbiota and microecological diversity were found among different clinical subgroups, and in particular, mixed infections with and resulted in lower lung microbiota diversity, suggesting that chlamydial infections shape the unique lung microbiota pathology, while mixed infections with different may have important effects on the composition and diversity of the lung microbiota. The present study provides possible evidences supporting the close correlation between chlamydial infection, altered microbial diversity in patients' lungs and clinical parameters associated with infection or inflammation in patients, which also provides a new research direction to better understand the pathogenic mechanisms of pulmonary infections caused by