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Biology subjects

zhou, z.

Publications and source records attributed to zhou, z..

5 recordsLinked to original sources

The role of falx cerebri in the selective vulnerability of splenium within the corpus callosum

The corpus callosum, the largest white matter tract connecting the cerebral hemispheres, is anatomically divided into the genu, midbody, and splenium. Among these subregions, the splenium is particularly vulnerable to traumatic injury, with the underlying biomechanics largely unknown. We hypothesized that the falx cerebri contributes to splenial vulnerability because of its anatomical proximity to the posterior corpus callosum and its substantially greater stiffness relative to brain tissue. To test this hypothesis, a high-resolution finite element head model with explicit representations of the corpus callosum subregions was used to simulate ten head impacts with and without an anatomically and mechanically detailed falx. Peak strain, strain rate, and shear stress were quantified and compared using linear mixed-effects models. The results showed the inclusion of the falx consistently increased strain, strain rate, and shear stress in the splenium relative to the genu and midbody, whereas this preferential splenial response was not consistently observed without the falx. Statistical analyses confirmed significant region-dependent effects, with falx-induced increases significantly greater in the splenium than in the other subregions (p < 0.05). These findings verified that the falx selectively amplifies mechanical loading within the splenium, providing a biomechanical explanation for its frequent involvement in neurotrauma patients.

bioengineering↗

Therapeutic Salmonella induces long-term protective trained immunity in NK cells against cancer metastasis

Trained immunity, a form of innate immune memory initially recognized in pathogen defense, has recently been reported to aid in combating cancer. Although trained immunity has been well-characterized in myeloid lineage cells, its presence in innate lymphoid cells, particularly natural killer (NK) cells, remains largely unexplored. Here, we report that a single dose of Salmonella YB1, an attenuated candidate anticancer vaccine strain, provides long-lasting protection against cancer metastasis in mice by inducing trained natural killer (NK) cells. Functional assays coupled with multiomics analysis revealed that Salmonella-trained NK (stNK) cells establish an enduring reprogrammed epigenome characterized by enhanced pro-survival signaling and immune effector functions, resulting in more potent IFN-{gamma} release and cytotoxicity upon secondary stimulation. We further revealed that IL-12 and IL-18 are essential but insufficient for this NK cell training effect. Crucially, stNK cells far outperform the common immune checkpoint therapies, including PD-1 and TIGIT blockade, in suppressing metastasis, underscoring the unique immunological mechanisms in combating metastasis. These findings uncover a novel long-term anti-metastatic function of trained immunity in NK cells, highlighting its potential as an effective antitumor strategy.

immunology↗

Electrospinning of hydroxypropyl chitosan nanofibers for bone regeneration application

To study the effect of electrospinning nanofiber mats synthesized using hydroxypropyl chitosan in conjugation with poly (vinyl alcohol) on the osteogenesis in MC3T3 cell, we fabricated different ratios of hydroxypropyl chitosan (HPCH) and poly (vinyl alcohol) to electrospin the nanofiber mats, the mechanical and physical properties of nanofiber mats were tested by using SEM, FT-IR and conventional methods. Then the effect of the electrospinning mats on osteogenesis in MC3T3 cell were evaluated by Alizarin Red stain, ALP stain and expression of relevant genes. We found that the nanofiber mats fabricated by hydroxypropyl chitosan (50%) and poly (vinyl alcohol)(50%) can induce osteoblast differentiation apparently in MC3T3 cell.

biochemistry↗

FLASH radiotherapy using high-energy X-rays: validation of the FLASH effect triggered by a compact single high-energy X-ray source device

PurposeThis preclinical study aimed to verify the FLASH effect of compact single high-energy X-ray source (CHEXs) and to explore whether three irradiations with single-gantry rotation two 30 s pauses can generate FLASH effect in mice. Materials and methodsThe absolute dose and pulsed beam of the CHEXs were measured using an EBTXD radiochromic film and fast current transformer. Healthy C57BL/6J female mice and a subcutaneous tumor model were irradiated under different conditions: sham (control), FLASH-RT (FLASH1: delivering the total dose in 1 fraction; FLASH3: delivering the total dose with two 30 second pauses to simulate a three-field delivery where the gantry rotation is occurring within 30 seconds), and conventional dose rate radiotherapy (CONV-RT). Various total doses were administered to the corresponding normal tissues (whole thorax, 30 Gy; whole abdomen, 12 Gy; and skin, 36 Gy) and tumors (CT26, 16.5 Gy; and LLC, 18 Gy). Survival status, normal tissue damage, and tumor growth suppression were recorded in each group. ResultsThe average dose rate of the CHEXs exceeded 40 Gy/s. For whole-thorax and skin irradiation, both FLASH1 and FLASH3 demonstrated protective effects. For whole-abdomen irradiation, FLASH1 exhibited a superior protective effect. No significant differences in tumor growth responses were observed between the FLASH1, FLASH3, and CONV-RT groups (P>0.05). ConclusionThis study confirmed that the FLASH effect could be triggered using CHEXs FLASH radiotherapy, and demonstrated that three irradiations with single gantry rotation two 30 s pauses can trigger the FLASH effect, indicating the potential benefit of CHEXs 3D conformal radiotherapy. Our findings indicate that further clinical trials on CHEXs are warranted.

cancer biology↗

The Genetic Heterogeneity of Multimodal Human Brain Age

The complex biological mechanisms underlying human brain aging remain incompletely understood, involving multiple body organs and chronic diseases. In this study, we used multimodal magnetic resonance imaging and artificial intelligence to examine the genetic architecture of the brain age gap (BAG) derived from gray matter volume (GM-BAG, N=31,557 European ancestry), white matter microstructure (WM-BAG, N=31,674), and functional connectivity (FC-BAG, N=32,017). We identified sixteen genomic loci that reached genome-wide significance (P-value<5x10-8). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and neuropsychiatric disorders and WM-BAG genes for cancer therapy. GM-BAG showed the highest heritability enrichment for genetic variants in conserved regions, whereas WM-BAG exhibited the highest heritability enrichment in the 5 untranslated regions; oligodendrocytes and astrocytes, but not neurons, showed significant heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several exposure variables on brain aging, such as type 2 diabetes on GM-BAG (odds ratio=1.05 [1.01, 1.09], P-value=1.96x10-2) and AD on WM-BAG (odds ratio=1.04 [1.02, 1.05], P-value=7.18x10-5). Overall, our results provide valuable insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. All results are publicly available at the MEDICINE knowledge portal: https://labs.loni.usc.edu/medicine.

genetics↗