Poröse MXene/CNT‐Mikrokugeln wurden von Xin Wang, Zhongwei Chen et al. in ihrem Forschungsartikel auf S. 2401 als Elektrokatalysator für hochleistungsfähige Lithium‐Schwefel‐Batterien entwickelt. ...Eine einzigartige O‐Ti‐C‐Grenzfläche wurde auf der MXene‐Oberfläche durch einen Sprühtrocknungsprozess und Wärmebehandlung konstruiert, um eine innere Spannung zu erzeugen, die eine Gitterverzerrung und eine Vergrößerung der Ti‐Ti‐Bindung induziert.
Complement factor properdin (
), encodes plasma glycoprotein, is a critical gene that regulates the complement pathway of the innate immune system. However, correlations of
in cancers remain unclear. ...In this study, the expression pattern and prognostic value of
in pan-cancer were analyzed via the Oncomine, PrognoScan, GEPIA and Kaplan-Meier plotters. In addition, we used immunohistochemical staining to validate CFP expression in clinical tissue samples. Finally, we evaluated the correlations between
and cancer immune infiltrates particularly in stomach adenocarcinoma (STAD) and lung adenocarcinoma (LUAD) by using GEPIA and TIMER databases. The results of database analysis and immunohistochemistry showed that the expression level of CFP in STAD and LUAD was lower than that in normal tissues. Low expression level of
was associated with poorer overall survival (OS), first progression (FP), post progression survival (PPS) and was detrimental to the prognosis of STAD and LUAD, specifically in stage 3, stage T3, stage N2 and N3 of STAD (
0.05). Moreover, expression of
had significant positive correlations with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (DCs) in STAD and LUAD. Furthermore, gene markers of infiltrating immune cells exhibited different
-related immune infiltration patterns such as tumor-associated-macrophages (TAMs). These results suggest that
can serve as a prognostic biomarker for determining prognosis and immune infiltration in STAD and LUAD.
Natural products exhibit structural complexity, diversity, and historical therapeutic significance, boasting attractive functions and biological activities that have significantly influenced drug ...discovery endeavors. The identification of target proteins of active natural compounds is crucial for advancing novel drug innovation. Currently, methods for identifying targets of natural products can be categorized into labeling and label-free approaches based on whether the natural bioactive constituents are modified into active probes. In addition, there is a new avenue for rapidly exploring the targets of natural products based on their innate functions.
This review aimed to summarize recent advancements in both labeling and label-free approaches to the identification of targets for natural products, as well as the novel target identification method based on the natural functions of natural products.
We systematically collected relevant articles published in recent years from PubMed, Web of Science, and ScienceDirect, focusing on methods employed for identifying protein targets of bioactive natural products. Furthermore, we systematically summarized the principles, procedures, and successful cases, as well as the advantages and limitations of each method.
Labeling methods allow for the direct labeling of target proteins and the exclusion of indirectly targeted proteins. However, these methods are not suitable for studying post-modified compounds with abolished activity, chemically challenging synthesis, or trace amounts of natural active compounds. Label-free methods can be employed to identify targets of any natural active compounds, including trace amounts and multicomponent mixtures, but their reliability is not as high as labeling methods. The structural complementarity between natural products and their innate receptors significantly increase the opportunities for finding more promising structural analogues of the natural products, and natural products may interact with several structural analogues of receptors in humans.
Each approach presents benefits and drawbacks. In practice, a combination of methods is employed to identify targets of natural products. And natural products' innate functions-based approach is a rapid and selective strategy for target identification. This review provides valuable references for future research in this field, offering insights into techniques and methodologies.
This review systematically summarizes recent advancements in target identification methods and technologies for natural products, providing a comprehensive overview of principles, procedures, successful cases, as well as the advantages and limitations of each approach. Display omitted
•Summarizing the recent progress in identifying targets of natural products.•These methods can be categorized into labeling and label-free approaches, as well as natural products' innate functions-based avenue.•Elucidation of the principle, workflow, successful cases of each method.•Comparing the pros and cons of different approaches.
Confined nanospaces provide a new platform to promote catalytic reactions. However, the mechanism of catalytic enhancement in the nanospace still requires insightful exploration due to the lack of ...direct visualization. Here, we report operando investigations on the etching and growth of graphene in a two-dimensional (2D) confined space between graphene and a Cu substrate. We observed that the graphene layer between the Cu and top graphene layer was surprisingly very active in etching (more than 10 times faster than the etching of the top graphene layer). More strikingly, at a relatively low temperature (∼530 °C), the etched carbon radicals dissociated from the bottom layer, in turn feeding the growth of the top graphene layer with a very high efficiency. Our findings reveal the in situ dynamics of the anomalous confined catalytic processes in 2D confined spaces and thus pave the way for the design of high-efficiency catalysts.
Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8+ T cells are ...affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8+ T cell death. Protective CD8+ T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness.
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•CD8+ T cell function and survival is impaired in HSAN-I patients with SPTLC2 mutation•Mouse CD8+ T cells require SPTLC2 to protect against viral infections•SPTLC2-mediated sphingolipid synthesis prevents mTORC1 hyperactivation and cell death•Sphingolipid supplementation restores SPTLC2-deficient CD8+ T cell effector function
SPTLC2 mutations are associated with the neurological disorder HSAN-I, in which patients get frequent infections, attributed to loss of pain sensation and failure to seek treatment for minor injuries. Wu et al. show that protective CD8+ T cell responses are defective in HSAN-I patients and that CD8+ T cells require SPTLC2-mediated sphingolipid synthesis to promote T cell metabolic fitness.
CD8
T cells become functionally impaired or "exhausted" in chronic infections, accompanied by unwanted body weight reduction and muscle mass loss. Whether muscle regulates T cell exhaustion remains ...incompletely understood. We report that mouse skeletal muscle increased interleukin (IL)-15 production during LCMV clone 13 chronic infection. Muscle-specific ablation of
enhanced the CD8
T cell exhaustion phenotype. Muscle-derived IL-15 was required to maintain a population of CD8
CD103
muscle-infiltrating lymphocytes (MILs). MILs resided in a less inflamed microenvironment, expressed more T cell factor 1 (Tcf1), and had higher proliferative potential than splenic T cells. MILs differentiated into functional effector T cells after reentering lymphoid tissues. Increasing muscle mass via muscle-specific inhibition of TGFβ signaling enhanced IL-15 production and antiviral CD8
T cell responses. We conclude that skeletal muscle antagonizes T cell exhaustion by protecting T cell proliferative potential from inflammation and replenishing the effector T cell progeny pool in lymphoid organs.
The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current ...cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1−PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses.
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•CMTM6 maintains the expression of CD58•CMTM6 co-regulates and interacts with both CD58 and PD-L1•Tumor cell-intrinsic CMTM6 and CD58 are important for antitumor T cell response
Miao et al. reveal CMTM6 as a positive regulator and interaction partner of CD58, an important costimulatory ligand in antitumor immune responses. They highlight the critical roles of tumor-intrinsic CMTM6 and CD58 expression in modulating T cell-tumor cell interactions and their potential impact on T cell-based immunotherapy.
T cells become functionally exhausted in tumors, limiting T cell-based immunotherapies. Although several transcription factors regulating the exhausted T (T
) cell differentiation are known, ...comparatively little is known about the regulators of T
cell survival. Here, we reported that the regulator of G protein signaling 16 (Rgs-16) suppressed T
cell survival in tumors. By performing lineage tracing using reporter mice in which mCherry marked Rgs16-expressing cells, we identified that Rgs16
CD8
tumor-infiltrating lymphocytes (TILs) were terminally differentiated, expressed low levels of T cell factor 1 (Tcf1), and underwent apoptosis as early as 6 days after the onset of Rgs16 expression.
deficiency inhibited CD8
T cell apoptosis and promoted antitumor effector functions of CD8
T cells. Furthermore,
deficiency synergized with programmed cell death protein 1 (PD-1) blockade to enhance antitumor CD8
T cell responses. Proteomics revealed that Rgs16 interacted with the scaffold protein IQGAP1, suppressed the recruitment of Ras and B-Raf, and inhibited Erk1 activation.
deficiency enhanced antitumor CD8
TIL survival in an Erk1-dependent manner. Loss of function of Erk1 decreased antitumor functions of
-deficient CD8
T cells.
mRNA expression levels in CD8
TILs of patients with melanoma negatively correlated with genes associated with T cell stemness, such as
,
, and
, and predicted low responses to PD-1 blockade. This study uncovers Rgs16 as an inhibitor of T
cell survival in tumors and has implications for improving T cell-based immunotherapies.
HIV-1 Nef is a multifunctional protein that optimizes virus spread and promotes immune evasion of infected cells to accelerate disease progression in AIDS patients. As one of its activities, Nef ...reduces the motility of infected CD4
T lymphocytes in confined space. In vivo, Nef restricts T lymphocyte homing to lymph nodes as it reduces the ability for extravasation at the diapedesis step. Effects of Nef on T lymphocyte motility are typically mediated by its ability to reduce actin remodeling. However, interference with diapedesis does not depend on residues in Nef required for inhibition of host cell actin dynamics. In search for an alternative mechanism by which Nef could alter T lymphocyte extravasation, we noted that the viral protein interferes with the polarization of primary human CD4
T lymphocytes upon infection with HIV-1. Expression of Nef alone is sufficient to disrupt T cell polarization, and this effect is conserved among lentiviral Nef proteins. Nef acts by arresting the oscillation of CD4
T cells between polarized and nonpolarized morphologies. Mapping studies identified the binding site for the Nef-associated kinase complex (NAKC) as critical determinant of this Nef activity and a NAKC-binding-deficient Nef variant fails to impair CD4
T lymphocyte extravasation and homing to lymph nodes. These results thus imply the disruption of T lymphocyte polarity via its NAKC binding site as a novel mechanism by which lentiviral Nef proteins alter T lymphocyte migration in vivo.
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