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Peripheral nerve regeneration after injury is still a clinical problem. The application of autologous nerve grafting, the gold standard treatment, is greatly restricted. Acellular nerve allografts (ANAs) are considered promising alternatives, but they are difficult to achieve satisfactory therapeutic outcomes, which may be attributed to their compact inherent ultrastructure and substantial loss of extracellular matrix (ECM) components. Regarding these deficiencies, this study developed an optimized multichannel ANA by a modified decellularization method. These innovative ANAs were demonstrated to retain more ECM bioactive molecules and regenerative factors, with effective elimination of cellular antigens. The presence of microchannels with larger pore size allowed ANAs to gain higher porosity and better swelling performance, which improves their internal ultrastructure. Their mechanical properties were more similar to those of native nerves. Moreover, the optimized ANAs exhibited good biocompatibility and possessed significant advantages in supporting the proliferation and migration of Schwann cells in vitro. The in vivo results further confirmed their superior capacity to promote axon regrowth and myelination as well as restore innervation of target muscles, leading to better functional recovery than the conventional ANAs. Overall, this study demonstrates that the optimized multichannel ANAs have great potential for clinical application and offer new insight into the further improvement of ANAs.

Persistence of quiescent leukemia stem cells (LSCs) after treatment most likely contributes to chemotherapy resistance and poor prognosis of leukemia patients. Identification of this quiescent cell population would facilitate eradicating LSCs. Here, using a cell‐tracing PKH26 (PKH) dye that can be equally distributed to daughter cells following cell division in vivo, we identify a label‐retaining slow‐cycling leukemia cell population from AML1‐ETO9a (AE9a) leukemic mice. We find that, compared with cells not maintaining PKH‐staining, a higher proportion of PKH‐retaining cells are in G0 phase, and PKH‐retaining cells exhibit increased colony formation ability and leukemia initiation potential. In addition, PKH‐retaining cells possess high chemo‐resistance and are more likely to be localized to the endosteal bone marrow region. Based on the transcriptional signature, HLA class II histocompatibility antigen gamma chain (Cd74) is highly expressed in PKH‐retaining leukemia cells. Furthermore, cell surface CD74 was identified to be highly expressed in LSCs of AE9a mice and CD34+ human leukemia cells. Compared to Lin−CD74− leukemia cells, Lin−CD74+ leukemia cells of AE9a mice exhibit higher stemness properties. Collectively, our findings reveal that the identified slow‐cycling leukemia cell population represents an LSC population, and CD74+ leukemia cells possess stemness properties, suggesting that CD74 is a candidate LSC surface marker. [ABSTRACT FROM AUTHOR]

Objective To analyze the risks and related influencing factors of early screening for lung cancer, and to study prognostic factors based on survival conditions, in order to ultimately provide baseline data for the prevention and treatment of lung cancer. Methods A cluster sampling method was used to select 40 to 75 year old registered residence residents in 10 districts and 6 counties of Zhengzhou City in 2020 as screening objects. Through voluntary participation and filling in evaluation questionnaires, high-risk groups of lung cancer were evaluated, and then three screening tests (tumor markers, low-dose spiral CT and lung function) were performed on high-risk groups. Finally, we will adopt an active and passive follow-up approach to collect information on diagnosed lung cancer patients. Statistically describe the screening data and describe the epidemiological results of different characteristic populations; Using multivariate logistic regression method for statistical analysis, compare the differences in various results of different factors. Results 50 128 cases of early screening for lung cancer in Zhengzhou City were evaluated in 2020, with a completion rate of 100.26%. The average age of the survey was (59.86 ± 17.67) years old, and the gender ratio was 0.81:1. The high-risk detection rate is 30.15%. Multivariate logistic regression analysis showed that males (smoking) (OR = 5.43, 95% CI: 5.20 ~ 5.67), individuals with a history of tobacco exposure (OR = 3.82, 95% CI: 3.67 ~ 3.98), first-degree relatives who had previously suffered from lung cancer (OR = 12.06, 95% CI: 11.02 ~ 13.20), and other populations were more susceptible to lung cancer (all P < 0.05). Conclusion Male (smoking), exposure to secondhand smoke, cancer in first-degree relatives, previous diagnosis of other tumors, symptoms of lung infection, "chest tightness, shortness of breath, and difficulty breathing in daily life", and "significant psychological trauma in the past 3 years" are independent risk factors for lung cancer, which should be given special attention and effective intervention measures should be taken. [ABSTRACT FROM AUTHOR]

Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson's disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8+ T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson's disease patients have a reduced frequency of CD8+ memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8+ T cell formation. We further uncovered that regulators of mitophagy, including Parkin and NIX, were up-regulated in response to interleukin-15 (IL-15) for supporting memory T cell formation. Mechanistically, Parkin suppressed VDAC1-dependent apoptosis in memory T cells. In contrast, NIX expression in T cells counteracted ferroptosis by preventing metabolic dysfunction resulting from impaired mitophagy. Together, our results indicate that the mitophagy machinery orchestrates survival and metabolic dynamics required for memory T cell formation, as well as highlight a deficit in T cell–mediated antiviral responses in Parkinson's disease patients. Editor's summary: During an immune response, T cells rely on mitochondria to support their evolving metabolic demands. Maintenance of mitochondrial health requires removal of damaged mitochondria via mitophagy, which can occur through PINK1/Parkin- or BNIP3L/NIX-mediated pathways. Using peripheral blood from patients with Parkinson's disease and LCMV-infected mice, Franco et al. examined the function of mitochondrial quality control in memory T cell responses. Patients with Parkinson's disease, which is associated with impairments in mitophagy, had fewer CD8+ memory T cells and impaired SARS-CoV-2–specific responses after vaccination. In LCMV-infected mice, Parkin suppressed VDAC1-dependent apoptosis of memory T cells, whereas NIX restrained ferroptosis by preventing metabolic dysfunction. These results demonstrate that key pathways of mitophagy support memory T cell responses by limiting distinct forms of cell death. —Claire Olingy [ABSTRACT FROM AUTHOR]