The depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. In vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. One hour/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype.

 m⁶A-mediated lncRNA PHKA1-AS1 promotes proliferation and metastasis of NSCLC via increasing ACTN4 stability. Increased m⁶A modification of lncRNA PHKA1-AS1 enhanced its expression in NSCLC, which in turn regulated the expression of epithelial‒mesenchymal transition-related proteins, leading to NSCLC metastasis. Additionally, high levels of PHKA1-AS1 could bind to the oncogene ACTN4, inhibiting its ubiquitination degradation and enhancing its protein stability, thus promoting NSCLC progression and metastasis.

Ferroptosis is an iron-dependent cell death form. In this study, we reveal a novel platinum(IV)–artesunate complex, which exhibits substantial bioactivity. For mechanism, the complex catalyzes lipid peroxidation, which ultimately induces ferroptosis in tumor cells. Meanwhile, the complex destroys ferroptosis defense system in mitochondria and cytoplasm. In summary, the complex has enormous clinical potential for ferroptosis-based cancer therapy in translational medicine.

Relationships between immune cell metabolism, epigenetics modulation, and cancer immunotherapy clinical efficiency. Epigenetic regulation (including DNA methylation, RNA methylation, histone modification, and chromatin remodeling) of immune cells can influence the differentiation and activity of immune cells, while metabolic status influences the energy supply and reactivity of immune cells, and they are participated in cancer immunotherapy and influenced clinical effect through immune cells as a bridge. (Me, methylation; U, ubiquitination; Ac, acetylation; P, phosphorylation).

The expression of CD44 is associated with stemness in cancer cells and activation in immune cells. In this review, we have mainly discussed the influence of CD44 expressing in cancer cells and therapeutic strategies through targeting CD44.

White adipose tissue undergoes dynamic changes in obesity, including adipose tissue pathological expansion, hypoxia, adipose tissue fibrosis, immune cells infiltration and finally leads to chronic low-grade inflammation and insulin resistance.

Cancer cachexia is a multifactorial syndrome that is responsible for the death of approximately 20% of cancer patients. It can effectively cause weight loss, skeletal muscle atrophy, and adipose tissue atrophy which can adversely affect the quality of life. However, effective drugs for cancer cachexia are still lacking. In this study, we have investigated whether brassinin (BSN) can affect cancer cachexia under in vitro and in vivo settings. We found that BSN effectively suppressed muscle atrophy by down-regulating the levels of Muscle RING-finger protein-1 and Atrogin-1, accompanied by increased expression of myosin heavy chain in cachexia-induced-C2C12 myotubes. BSN inhibited adipocyte atrophy by inducing adipogenesis in cachexia-induced 3T3-L1 adipocytes. We also noted that BSN can down-regulate signaling transducer and activator of transcription 3 activation. Moreover, it was found that BSN inhibited weight loss in mice and exerted anti-cachexic actions. Overall, our observations indicate that BSN can attenuate cancer cachexia and might function as a novel agent for the treatment of cancer cachexia.

Application of liquid biopsy in immunotherapy of tumors. This schematic illustrates the advantages of liquid biopsy over tissue biopsy, such as minimally invasive and reproducible. As an essential alternative or complementary tool to tissue biopsy, liquid biopsy obtains a tumor profile by analyzing tumor-derived components from the circulation (e.g., circulating tumor cells, circulating tumor DNA, exosomes, etc.) and can be used in critical fields, such as screening for immunotherapy beneficiaries, indicating disease progression, predicting prognosis, and so on.

Schematic description of the main molecular mechanism involved in the critical role of TTYH3 in the regulation of CRC migration and angiogenesis via ceRNA mechanism. TTYH3 facilitates the advancement of CRC via interacting with HDAC7 through ceRNA crosstalk, namely by binding miR-1271-5p, rather than relying on its chloride ion channels activity.

X chromosome showing TSGs position (right) and functional effects of tumorigenic miRNAs (onco-miRs) and tumor-inhibitory miRNAs (left).

We applied individual brain connectome in chronic steno-occlusive vasculopathy to map both ischemic symptoms and their postbypass changes. Using multimodal parcellation with connectivity-based and pathological distortion-independent approach, areal MR features of brain connectome were generated with three measurements at the single-subject level. Machine-learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes. Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome.

TP53 comutation was associated with poor outcomes in non-small cell lung cancer patients treated with third-generation epidermal growth factor receptor tyrosine kinase inhibitors. Notably, subgroup analysis has revealed that patients with TP53 mutations in the alpha helix region had shorter median OS compared with those with TP53 mutations in other structural regions. Similar findings were confirmed in another GENIE cohort.

CircPIK3C2A/miR-31-5p/TFRC axis promotes ferroptosis and exacerbates myocardial injury through inducing iron overload.

MPA-CF₃ destabilizes coatomer subunit zeta-1 (COPZ1) upon binding and disrupts the interaction of COPZ1 with the EV-A71 2C protein, resulting in blocking of coat protein complex I (COPI) coat-mediated transport of 2C to ER and subsequent inhibition of EV-A71 replication.

Targeted DNA and TCR sequencing were performed on tumor biopsy specimens from ICI-treated NSCLC patients. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score. The predictive value and prognostic role of TMR was assessed in NSCLC patients receiving immunotherapy. The performance of TMR score was confirmed in the two external validation cohorts from MD Aderson Cancer Center (MDACC).

Antileukemic PROteolysis-TArgeting Chimeras (PROTACs) induce degradation of leukemia-associated targets, including resistance-conferring mutant forms. PROTACs against leukemia have increased dramatically. Most antileukemic PROTACs, through an event-driven mechanism, degrade the target potently, quickly, selectively, and with a long duration of action in vitro and in vivo, overcoming the difficulties of conventional inhibitors. Currently, six antileukemic PROTACs are in phase I/II of clinical trials .

MY was found to protect aged mice against the loss of muscle mass and strength through scavenging ROS accumulation to rebuild the redox homeostasis. Combining biophysical and pharmacological profiles, peroxiredoxin 5 was discovered and validated as the direct target of MY. Furthermore, mechanistic studies showed that MY reduced reactive oxygen species accumulation and damaged mitochondrial DNA in myotubes through activating peroxiredoxin 5.

Tumor-infiltrating CD4⁺ T cells in OPSCC were categorized into the immune-promoting module (Module 1) and the immunosuppressive module (Module 2).The functions of Module 1 and Module 2 were positively associated with the T cell exhaustion states.Blocking the exhaustion progression of the bidirectional modules of CD4⁺ T cells alter the functional balance between Module 1 and Module 2 exhausted cells.

Transcriptome and metabolome profiling of graft tissues and recipient plasma revealed that MaS-related GF molecules were enriched in ferroptosis, peroxisome, and Peroxisome proliferator-activated receptors (PPAR) pathways. L-glutathione biosynthesis metabolites were depleted and transferrin-centric network regulated MaS-related GF. Decreased transferrin impairs anti-oxidative capacity via HNF4A/HIF1A. Increased circulating aromatic amino acid amplifies MaS-induced GF risk. MaS-induced GF stems from impaired anti-oxidative capacity via comprehensive regulatory networks.

Ageing in stem or progenitor cells often results in cellular apolarity, which impedes their mature differentiation. However, the induction of apolarity in aged myeloid-derived suppressor cells (MDSCs) remains unexplored. This study reveals that the TNFR2 hyperexpression, triggered by either TNF-α or IL-6—two factors associated with the senescence-associated secretory phenotype (SASP), causes JNK-induced apolarity and inhibits differentiation in aged MDSCs.

We found that the LPS translocated from the gut was able to trigger Caspase 11/GSDMD induced pyroptosis of macrophages in lupus-prone mice. The pyroptotic macrophages were able to facilitate the differentiation of plasma cell, by which process the intestinal disorders contributed to the development of lupus. We also confirmed that Caspase 11-inhibition was a potential therapy for lupus. .

CircMALAT1 modulated the ubiquitination and degradation of the MSI2 protein signaling with ESCC CSCs and accelerated malignant progression of ESCC.

Through the optimization of the structural proteins of coronavirus virus-like particle (VLP) pseudotyped virus, we successfully constructed high titer the VLP pseudotyped virus variant. We optimized the conditions for neutralizing antibodies and validated the methodology. We have established a detection method for neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VLP pseudotyped virus, which shows good consistency with authentic viruses and suitable for detecting various variants.