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Nacre, the iridescent inner layer of mollusk shells, has long been traditionally used in medicine. While we have previously demonstrated its anti-aging effects on muscle and skin, its impact on pancreatic dysfunction and glucose metabolism remains unclear. In this study, we aimed to isolate and identify an active component from nacre extract that improves glucose metabolism and to evaluate its potential to prevent or ameliorate pancreatic dysfunction and glucose metabolic abnormalities in a D-galactose-induced aging mouse model. A polysaccharide component was successfully isolated using a combination of reverse-phase and ion-exchange chromatography. Structural analyses revealed that it was primarily composed of glucose, mannose, and rhamnose, which together accounted for approximately 87% of the total monosaccharide content. Further characterization by FT-IR spectroscopy and MALDI-TOF-MS confirmed its identity as a neutral polysaccharide with glycosidic linkages and an estimated molecular weight of approximately 5000 Da. Intraperitoneal administration of this polysaccharide significantly improved glucose tolerance and prevented a decline in serum insulin levels in D-galactose-induced aging mice. Immunohistochemical analysis of pancreatic tissues revealed that the polysaccharide preserved insulin expression and suppressed the D-galactose-induced upregulation of cellular senescence and apoptosis markers. These findings suggest that this nacre-derived polysaccharide effectively mitigates pancreatic dysfunction and glucose metabolic dysfunction, indicating its potential as a natural therapeutic agent for age-related metabolic disorders.

Shells are composed of two types of calcium carbonate polymorphs—the prismatic layer and the nacreous layer. Pearls, composed of the nacreous layer, have been used in Chinese medicine since ancient times. We have previously shown that extracts from the nacreous layer improves scopolamine-induced memory impairment. However, whether pearl ameliorates cognitive disorders induced by amyloid-β 1–40 (Aβ1–40) has not been elucidated. In this study, we investigated whether nacre extract improves memory impairment induced by intracerebroventricular injection of Aβ1–40. Administration of nacre extract led to recovery from Aβ1–40-induced impairments in object recognition, short-term memory, and spatial memory. Nacre extract reversed the increase in lipid peroxidation caused by Aβ1–40 in the cerebral cortex by increasing the expression of catalase and superoxide dismutase. In addition, nacre extract recovered the expression and phosphorylation of cyclic AMP response element-binding protein (CREB), which decreased with Aβ1–40 treatment, and increased the expression of brain-derived neurotrophic factor and neuropeptide Y, which are regulated by CREB. Nacre extract also suppressed acetylcholine esterase activity and Aβ1–40-induced tau phosphorylation. Histochemical analysis of the hippocampus region showed that the nacre extract protected against Aβ1–40-induced neuronal loss in the hippocampus. These results suggest that nacre extract protects against Aβ1–40-induced neuronal cell death by suppressing oxidative stress and increasing the expression and phosphorylation of CREB. Graphical abstract

An all-optical network is identified as a promising infrastructure for fast and energy-efficient communication. Recently, it has been shown that its quantum version based on ‘all-photonic quantum repeaters’—inheriting, at least, the same advantages—expands its possibility to the quantum realm, that is, a global quantum internet with applications far beyond the conventional Internet. Here we report a proof-of-principle experiment for a key component for the all-photonic repeaters—called all-photonic time-reversed adaptive (TRA) Bell measurement, with a proposal for the implementation. In particular, our TRA measurement—based only on optical devices without any quantum memories and any quantum error correction—passively but selectively performs the Bell measurement only on single photons that have successfully survived their lossy travel over optical channels. In fact, our experiment shows that only the survived single-photon state is faithfully teleported without the disturbance from the other lost photons, as the theory predicts. Storage-free quantum repeaters represent a viable alternative to quantum-memory-based ones. Here, the authors propose a modified scheme for Bell state measurements which reduces the necessary resources for realising such an all-photonic repeater, and show a proof-of-principle implementation.

Purpose Acute liver failure is a life-threatening condition for which ABO-incompatible living donor liver transplantation (ABOi-LDLT) is sometimes the only life-saving treatment option. We reviewed a single-center experience of adult ABOi-LDLT treatment for acute liver failure (ALF). Methods Preoperative treatment, immune indices (B cell marker, anti-donor blood-type antibody), and postoperative outcomes were compared between ALF and non-ALF groups. Results There were 5 and 33 patients in the ALF and non-ALF groups, respectively. The ALF group received higher doses of steroids, underwent more rounds of plasma exchange (PE), and underwent transplantation for ALF with a shorter interval following preoperative rituximab (RTx) administration (median: 2 vs 13 days; P  < 0.05) than the non-ALF group. Preoperatively, CD19-positive lymphocytes in the peripheral blood were sufficiently depleted in all of the non-ALF group patients, whereas they were poorly depleted in the ALF group. Postoperatively, neither group suffered anti-donor blood-type antibody titer rebound or antibody-mediated rejection. The ALF group had a comparable 5-year survival rate to the non-ALF group (80.0% vs 77.9%). Conclusions Despite the delayed preoperative administration of RTx, the ALF group showed an uneventful immunological response and acceptable long-term survival rate. Thus, ABOi-LDLT seems a viable treatment option for ALF.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O‐glycan‐binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV‐counting system (ExoCounter). This retrospective study analyzed changes in ACA‐positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre‐ and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19‐9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA‐positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA‐positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence‐free survival (RFS) of patients with higher ACA‐positive EVs were significantly shorter than those with lower ACA‐positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA‐positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA‐positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period. This retrospective, observational study developed a system to predict poor prognosis of pancreatic ductal adenocarcinoma after surgery based on the change in Amaranthus caudatus agglutinin‐positive extracellular vesicles in patients' sera before surgery and after surgical resection.

Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell–cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell–cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.

The mucin‐type sialoglycoprotein podoplanin (aggrus) is involved in tumor cell‐induced platelet aggregation and tumor metastasis. C‐type lectin‐like receptor‐2 (CLEC‐2) was recently identified as an endogenous receptor of podoplanin on platelets. However, the pathophysiological importance and function of CLEC‐2 have not been elucidated. Here we clarified the pathophysiological interaction between podoplanin and CLEC‐2 in vitro and in vivo. Using several deletion mutants of CLEC‐2 expressed as Fc chimeras, we first identified an important podoplanin‐recognition domain in CLEC‐2. Furthermore, the podoplanin–CLEC‐2 interaction was confirmed using several deletion mutants of podoplanin expressed as Fc chimeras. Not only the disialyl‐core1‐attached glycopeptide but also the stereostructure of the podoplanin protein was found to be critical for the CLEC‐2‐binding activity of podoplanin. We next synthesized various glycopeptides of podoplanin that included both the platelet aggregation‐stimulating domain and O‐glycan on Thr52. Interestingly, a disialyl‐core1‐attached glycopeptide was recognized specifically by CLEC‐2. Moreover, the anti‐podoplanin monoclonal antibody NZ‐1 suppressed both the podoplanin–CLEC‐2 interaction and podoplanin‐induced pulmonary metastasis, suggesting that CLEC‐2 is the first pathophysiological receptor of podoplanin to be identified. In summary, we clarified the molecular interaction in vitro and in vivo between a platelet aggregation‐inducing factor, podoplanin, and its specific pathophysiological receptor on platelets, CLEC‐2. Podoplanin and CLEC‐2 might represent promising therapeutic targets in cancer metastasis. (Cancer Sci 2008; 99: 54–61)

Purpose Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. Methods We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a “pooled” cohort of cases identified in our institute and reported in the literature. Results HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. Conclusion Early-onset HVOD developing within 14 days after LT has a poor prognosis.

PurposeTo evaluate the early remission rate of type 2 diabetes mellitus (T2DM) after laparoscopic sleeve gastrectomy (LSG) and establish a preliminary scoring system that predicts T2DM remission.MethodsWe assessed the outcomes of 49 morbidly obese patients with T2DM who underwent LSG between 2008 and 2018. The prognostic factors for T2DM remission 1 year post-LSG were identified and an original scoring system was established. We validated our scoring system by comparing it with the individualized metabolic surgery score and the ABCD score.ResultsThe patients’ mean body weight loss and percentage of excess weight loss were 34.4 kg and 59.4%, respectively, while the T2DM remission rate was 77.5%. The serum insulin level and the T2DM duration were independent predictive factors, the receiver-operating characteristic (ROC) curves for which revealed cutoff values of 12.7 ng/mL and 72 months, respectively. We set our system’s score range at 0–2, whereby patients with higher scores have a good T2DM remission prognosis, as higher insulin levels, and/or shorter T2DM duration. Our scoring system had accuracy levels similar to those of the ABCD score with a simple stratification.ConclusionOur preliminary scoring system attains a good level of accuracy for predicting T2DM remission.

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole‐exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first‐degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer. Patients with intraductal papillary mucinous neoplasm with a family history of pancreatic cancer are more likely to develop malignancy in a shorter period than those without a family history. Of 18 patients with a strong family history of pancreatic cancer, three previously known susceptibility genes and one novel candidate gene were identified.