CUSABIO Quarterly Citations Review: Q3 2024, Over 720 Citations with an Impact Factor Exceeding 3500, Totaling 23,600 Articles!

This study integrated plasma and fecal metabolomics to identify functional metabolites in the progression of colorectal cancer (CRC) and colorectal adenoma, and explored their potential as early diagnostic biomarkers. The study found that the increase of certain metabolites (such as oleic acid) in CRC is associated with disease progression, while the decrease of other metabolites (such as allocholic acid) is related to disease suppression. These metabolites can directly bind to tumor cell receptors to modulate downstream oncogenic pathways. Clinically, a panel of 17 plasma metabolites was established to accurately diagnose CRC and adenoma. The results highlight the key role of metabolites in CRC progression and demonstrate the potential of plasma metabolites as biomarkers for non-invasive early diagnosis of CRC patients.

This article reports a quantitative one-pot iterative living polymerization technique for precise control over the molecular structure and monomer sequence of protein-polymer conjugates. Using this technique, the research team successfully developed a series of sequence-controlled protein-multiblock polymer conjugates, significantly enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations were performed to reveal the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution. This work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions, promising candidates for disease treatment.

This study reports a novel interferonopathy caused by a dominant negative mutation in the REXO2 gene, which encodes a mitochondrial exonuclease critical for the regulation of mitochondrial RNA. The heterozygous de novo mutation (p.T132A) impairs REXO2's ability to cleave RNA and inhibits the activity of wild-type REXO2 in a dominant-negative manner. This leads to the accumulation of mitochondrial dsRNA in the cytosol, activation of the MDA5 pathway, and induction of a type I interferon gene signature. The findings uncover a critical role of REXO2 in immune homeostasis and suggest potential therapeutic avenues for related inflammatory conditions.

This study developed zinc oxide nanoparticles (ZnO NPs) with catalase-like nanozyme activity and near-infrared light response for enhanced photodynamic therapy (PDT) efficacy. The ZnO NPs can convert 808 nm near-infrared light into 401 nm visible light to excite the photosensitizer Ce6, enabling deep-tissue PDT. Moreover, as nanozymes with peroxidase-like activity, ZnO NPs can decompose hydrogen peroxide in tumors to produce oxygen, thereby alleviating the hypoxic tumor environment. The study also found that ZnO NPs can induce ferroptosis and autophagy in tumor cells without light, thereby enhancing the antitumor immune response. These findings indicate that ZnO NPs have great potential in improving PDT effects, promoting antitumor immune responses, and serving as an effective tumor treatment strategy.

This article investigates whether SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease. The researchers used human dopaminergic neurons and hACE2 transgenic mouse models to conduct the study. The findings reveal that SARS-CoV-2 infection spreads to the brain via the nasal cavity and worsens the degeneration of dopaminergic neurons treated with 伪-synuclein preformed fibrils. Moreover, the neuroinflammatory response in SARS-CoV-2-infected mice persists for over 60 days even after the virus is undetectable in the brain. These findings highlight the potential long-term neurodegenerative effects of COVID-19 on Parkinson's disease.

This article investigates the role of heat shock protein 47 (HSP47) in brain metastasis of lung and breast cancer. The study found that upregulation of HSP47 in tumor cells promotes collagen deposition, which suppresses anti-tumor immune responses through polarization of M2 microglia, thereby facilitating brain metastasis. Using the HSP47 inhibitor Col003 can restore anti-tumor immunity and enhance the efficacy of anti-PD-L1 immunotherapy for brain metastases. The research indicates that HSP47 is a critical determinant of M2 microglial polarization and immunosuppression, and targeting the HSP47-collagen axis is a promising therapeutic strategy for treating brain metastatic tumors.

This article explores the role of bone marrow adipocytes (BMAds) in skeletal aging and finds that exercise can inhibit the secretion of PCNA clamp-associated factor (PCLAF) from bone marrow macrophages to suppress BMAd senescence, thereby alleviating skeletal aging. The study also discovers that PCLAF promotes the senescence of BMAds by binding to the ADGRL2 receptor and inhibiting the AKT/mTOR signaling pathway, a process that promotes bone loss. In addition, the study develops a PCLAF-neutralizing antibody and confirms its therapeutic potential in improving skeletal health in old mice. In summary, the research reveals PCLAF as an inducer of BMAd senescence and provides a promising therapeutic strategy for treating age-related osteoporosis.

This article investigates how oxidative stress can promote antitumor immune responses by altering oxidative post-translational modifications (oxPTM) of melanoma-associated antigens MART and PMEL. The study found that cold plasma technology-treated oxidized MART (oxMART) and oxidized PMEL (oxPMEL) significantly enhance the activation and proliferation of cytotoxic T-cell subpopulations. The results showed that the oxMART vaccine increased the activity of cytotoxic central memory T-cells, while the oxPMEL vaccine led to increased proliferation of cytotoxic effector T-cells. Additionally, the study developed a PCLAF-neutralizing antibody, demonstrating its therapeutic potential in improving skeletal health in old mice. This research provides, for the first time, evidence of the importance of oxidative modifications of two melanoma-associated antigens in inducing anticancer immunity.

The article presents a bioactive patch for rotator cuff repair by enhancing tendon-to-bone healing. The research team utilized bioactive components from the umbilical cord (UC) to fabricate a novel tissue engineering scaffold that modulates the tendon-bone interface (TBI) healing microenvironment in vitro, promoting cell proliferation, migration, inflammation suppression, and chondrogenic differentiation. In vivo validation in a canine model and short-term clinical trial outcomes demonstrated the efficacy of the UC scaffold in promoting TBI reconstruction and rotator cuff repair. This study provides key insights for clinical

This study explores the relationship between the imbalance of Th1/Th2 cells in peripheral blood and the dynamics of microglia state in the central nervous system (CNS), and how this relationship affects the progression of temporal lobe epilepsy (TLE). The study found an imbalance of Th1/Th2 cell subsets in the peripheral blood of TLE patients, accompanied by the release of related cytokines. It is proposed that this peripheral imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In a lithium-pilocarpine-induced TLE rat model, a peripheral Th1/Th2 imbalance and corresponding central and systemic responses were observed. Notably, CD4+ T cells infiltrated through the compromised blood-brain barrier (BBB) and were spatially close to microglia around epileptic foci. Depletion and reinfusion of CD4+ T cells via intravenous injection modulated microglial state dynamics and altered the secretion of neuroinflammatory cytokines. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. The study emphasizes the significance of Th1/Th2 imbalance in modulating the "systemic-central" response in TLE and highlights Notch1 as a potential therapeutic target.