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The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and is greatly reduced in Mafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced in Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased in Mafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q.

Purposes Delayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes. Methods We reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC. Results Between 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra—and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC. Conclusions In view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC.

Ultraviolet (UV) irradiation offers an effective and convenient method for the disinfection of pathogenic microorganisms. However, UV irradiation causes protein and/or DNA damage; therefore, further insight into the performance of different UV wavelengths and their applications is needed to reduce risks to the human body. In this paper, we determined the efficacy of UV inactivation of the SARS-CoV-2 omicron BA.2 and BA.5 variants in a liquid suspension at various UV wavelengths by the 50% tissue culture infection dose (TCID 50 ) method and quantitative polymerase chain reaction (qPCR) assay. The inactivation efficacy of 220 nm light, which is considered safe for the human body, was approximately the same as that of health hazardous 260 nm light for both BA.2 and BA.5. Based on the inactivation rate constants determined by the TCID 50 and qPCR methods versus the UV wavelength, the action spectra were determined, and BA.2 and BA.5 showed almost the same spectra. This result suggests that both variants have the same UV inactivation characteristics.

Background3C/Ritscher-Schinzel syndrome is characterised by congenital cranio-cerebello-cardiac dysplasia, where CCDC22 and WASHC5 are accepted as the causative genes. In combination with the retromer or retriever complex, these genes play a role in endosomal membrane protein recycling. We aimed to identify the gene abnormality responsible for the pathogenicity in siblings with a 3C/Ritscher-Schinzel-like syndrome, displaying cranio-cerebello-cardiac dysplasia, coloboma, microphthalmia, chondrodysplasia punctata and complicated skeletal malformation.MethodsExome sequencing was performed to identify pathogenic variants. Cellular biological analyses and generation of knockout mice were carried out to elucidate the gene function and pathophysiological significance of the identified variants.ResultsWe identified compound heterozygous pathogenic variants (c.1097dup; p.Cys366Trpfs*28 and c.2755G>A; p.Ala919Thr) in the VPS35L gene, which encodes a core protein of the retriever complex. The identified missense variant lacked the ability to form the retriever complex, and the frameshift variant induced non-sense-mediated mRNA decay, thereby confirming biallelic loss of function of VPS35L. In addition, VPS35L knockout cells showed decreased autophagic function in nutrient-rich and starvation conditions, as well as following treatment with Torin 1. We also generated Vps35l−/− mice and demonstrated that they were embryonic lethal at an early stage, between E7.5 and E10.5.ConclusionsOur results suggest that biallelic loss-of-function variants in VPS35L underlies 3C/Ritscher-Schinzel-like syndrome. Furthermore, VPS35L is necessary for autophagic function and essential for early embryonic development. The data presented here provide a new insight into the critical role of the retriever complex in fetal development.

Purpose This single-institution retrospective cohort study was conducted to assess the prognostic significance of perioperative changes in the prognostic nutritional index (PNI) in patients who underwent surgery for non-small cell lung cancer (NSCLC). Methods Clinicopathological data were collected from 441 patients who underwent lobectomy for NSCLC between 2010 and 2016.The PNI ratio (postoperative PNI/preoperative PNI) was used as an indicator of perioperative PNI changes. Prognostic differences were investigated based on PNI ratios. Results The optimal cut-off value of the PNI ratio for overall survival (OS) was set at 0.88 using a receiver operating characteristic curve. The PNI ratio was inversely related to a high smoking index, interstitial lung disease, and postoperative pulmonary complications. The 5-year OS rates for the high vs. low PNI ratio groups were 88.2% vs. 68.5%, respectively (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.90–4.86). Multivariable analysis revealed that a low PNI ratio was significantly associated with poor prognosis (HR: 2.94, 95% CI: 1.77–4.87). The PNI ratio was a more sensitive indicator than postoperative PNI status alone for identifying patients at high risk of mortality, particularly those with non-lung cancer causes. Conclusion The perioperative PNI change is a significant prognostic factor for patients with NSCLC.

Purpose To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. Methods Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart–Lung Transplantation. Results The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). Conclusions The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

Reelin is a secreted protein that plays versatile roles in neuronal development and function. The strength of Reelin signaling is regulated by proteolytic processing, but its importance in vivo is not yet fully understood. Here, we generated Reelin knock-in (PA-DV KI) mice in which the key cleavage site of Reelin was abolished by mutation. As expected, the cleavage of Reelin was severely abrogated in the cerebral cortex and hippocampus of PA-DV KI mice. The amount of Dab1, whose degradation is induced by Reelin signaling, decreased in these tissues, indicating that the signaling strength of Reelin was augmented. The brains of PA-DV KI mice were largely structurally normal, but unexpectedly, the hippocampal layer was disturbed. This phenotype was ameliorated in hemizygote PA-DV KI mice, indicating that excess Reelin signaling is detrimental to hippocampal layer formation. The neuronal dendrites of PA-DV KI mice had more branches and were elongated compared to wild-type mice. These results present the first direct evidence of the physiological importance of Reelin cleavage.

Purpose To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. Methods Patients’ data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. Results Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient’s age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. Conclusion The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

Purpose Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC). Methods The present study included 422 patients with stage I–IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively. Results One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching. Conclusion Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis.

Purpose To investigate the surgical outcomes and postoperative survival prognostic factors of intractable secondary spontaneous pneumothorax. Methods A total of 95 patients who underwent thoracoscopic surgery for intractable secondary spontaneous pneumothorax between April 2010 and March 2020 were included in this study. These patients were classified into interstitial pneumonia and non-interstitial pneumonia groups, and a comparative study was performed on surgical outcomes and postoperative survival prognostic factors. Results There was no difference in the 1-year overall survival rate between the two groups. However, the 3-year overall survival rate was significantly lower in the interstitial pneumonia group than in the non-interstitial pneumonia group. The differences in short-term surgical outcomes (persistent air leakage, postoperative complications, etc.) were not significant between the two groups. Univariate analysis revealed that the drainage period, the development of postoperative complications, and recurrence were significant independent postoperative survival prognostic factors for all cases. Postoperative complications were the only associated postoperative survival prognostic factor for interstitial pneumonia pneumothorax in the multivariate analysis. Conclusion The development of postoperative complications can cause poor postoperative survival prognosis of intractable secondary spontaneous pneumothorax due to interstitial pneumonia.