Robust Spirobifluorene Core Based Hole Transporters with High Mobility for Long-Life Green Phosphorescent Organic Light-Emitting Devices.

Using a tailored high triplet energy hole transport layer (HTL) is a suitable way to improve the efficiency and extend the lifetime of organic light-emitting devices (OLEDs), which can use all molecular excitons of singlets and triplets. In this study, dibenzofuran (DBF)-end-capped and spirobifluorene (SBF) core-based HTLs referred as TDBFSBF1 and TDBFSBF2 were effectively developed. TDBFSBF1 exhibited a high glass transition temperature of 178 °C and triplet energy of 2.5 eV. Moreover, a high external quantum efficiency of 22.0 %, long operational lifetime at 50 % of the initial luminance of 89,000 h, and low driving voltage at 1000 cd m-2 of 2.95 V were achieved in green phosphorescent OLEDs using TDBFSBF1. Further, a high-hole mobility µh value of 1.9×10-3  cm2 V-1 s-1 was recorded in TDBFSBF2. A multiscale simulation successfully reproduced the experimental µh values and indicated that the reorganization energy was the primary factor in determining the mobility differences among these SBF core based HTLs.

Clinical significance of postoperative subcutaneous emphysema after video-assisted thoracoscopic surgery for esophageal cancer.

BACKGROUND: Postoperative subcutaneous emphysema (SE) is a possible complication of thoracoscopic or laparoscopic surgery. This study investigated the risk factors and clinical significance of SE after video-assisted thoracoscopic surgery for esophageal cancer (VATS-e). METHODS: This study included 135 patients who underwent VATS-e with artificial CO2 pneumothorax. Based on the X-ray images on the first postoperative day, patients were divided into two groups: N/L group (no SE or SE localized at the thoracic area, n = 65) and SE group (SE extended to the cervical area, n = 70). We compared clinicopathological features, surgical findings, and short-term outcomes between the two groups. RESULTS: In SE group, there were more patients who received neoadjuvant chemotherapy compared to N/L group. SE group had significantly lower preoperative body mass index. SE group had more frequently two-lung ventilation than N/L group. Multivariate analysis demonstrated that low BMI, NAC, and two-lung ventilation were independent risk factors for SE extended to the cervical area. Although pulmonary complication was relatively frequent in SE group, there were no significant differences in surgical outcomes between two groups, and all patients had SE disappeared within 21 days without serious complications. CONCLUSIONS: Despite extension to the cervical area, SE had a modest impact on the short-term result of VATS-e with artificial CO2 pneumothorax.

Four Dibenzofuran-Terminated High-Triplet-Energy Hole Transporters for High-Efficiency and Long-Life Organic Light-Emitting Devices.

The weak stability of a hole-transporter upon approaching the anion state is one of the major bottlenecks for developing long-life organic light-emitting devices (OLEDs). Therefore, in this study, we developed a series of thermally and electrically stable hole-transporters that are end-capped with four dibenzofuran units. These materials exhibit i) high bond dissociation energy (BDE) toward the anion state, ii) a high glass transition temperature (Tg >130 °C), and iii) high triplet energy (ET >2.7 eV), thereby enabling approximately 20 % high external quantum efficiency (EQE) and significantly prolonging the stability of both thermally activated delayed fluorescent (TADF) and phosphorescent OLEDs with an operation lifetime at 50 % (LT50 ) of 20 000-30 000 h at 1000 cd m-2 . In addition, investigating their structure-property relationship revealed that ionization potential (IP ), BDE, and Tg are critical prerequisites for the hole-transporter to prolong lifetime in OLEDs.

Clinical Relevance of Tissue and Serum Human Epidermal Growth Factor Receptor 2 Expression in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: Serum and tissue human epidermal growth factor receptor 2 (HER2) levels were evaluated in resected esophageal squamous cell carcinoma (SCC) specimens to assess the relationship between HER2 expression and long-term prognosis. METHODS: We included 95 patients who underwent esophagectomy for esophageal SCC. The serum HER2-extracellular domain (sHER2-ECD) levels were measured using an ELISA kit. A time-dependent receiver operating characteristics curve for censored survival outcomes was constructed to estimate the optimal cut-off value of sHER2-ECD (set at 4211 pg/mL). Immunohistochemical (IHC) staining was performed for HER2, and specimens were classified based on low (0 or 1+) or high HER2-IHC expression (2+ or 3+). RESULTS: Patients with low sHER2-ECD levels showed poorly differentiated tumors, nodal involvement, and larger tumor size more frequently compared to patients with high sHER2-ECD levels. There were no differences in clinicopathological features based on HER2-IHC expression. Between patients with high and low HER2-IHC expression, the former group showed significantly higher sHER2-ECD levels. Patients with high sHER2-ECD levels had significantly favorable relapse-free survival (RFS) and overall survival (OS) compared to those with low sHER2-ECD levels. Conversely, patients with high HER2-IHC expression had significantly poorer RFS than did patients with low HER2-IHC expression, although no difference was observed in OS. Additionally, patients with high sHER2-ECD levels and low HER2-IHC expression had the highest OS and RFS among the patients studied. CONCLUSIONS: The correlation among sHER2-ECD levels, HER2-IHC expression, and prognosis was demonstrated. Prospective studies are required to validate the impact of serum and tissue HER2 expression in esophageal SCC prognosis.

Correlation Between Immunoinflammatory Measures and Periostin Expression in Esophageal Squamous Cell Carcinoma: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Immunoinflammatory measures such as the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the C-reactive protein (CRP)-albumin ratio (CAR) are useful prognostic measures in various malignancies. However, no study has investigated the correlation of these measures with microenvironmental inflammation. Periostin (POSTN), a small extracellular matrix protein, strongly associates with cancer microenvironmental inflammation. The current study investigated the correlation of NLR, PLR, and CAR with periostin expression in esophageal squamous cell carcinoma (ESCC). METHODS: The study retrospectively evaluated preoperative NLR, PLR, and CAR hematologically and POSTN immunohistochemically in 171 patients. The correlation of immunoinflammatory measures, POSTN expression, and survival outcomes was measured. RESULTS: The study showed a significant correlation of POSTN-positive expression with poor overall survival (OS) (P < 0.0001) and recurrence-free survival (RFS) (P = 0.03). The POSTN-positive group had higher PLR (189.6 ± 8 vs. 159.3 ± 12; P = 0.04) and CAR (0.36 ± 0.06 vs. 0.14 ± 0.09; P < 0.05) than the POSTN-negative group, whereas NLR did not differ between the two groups (3.27 ± 0.19 vs. 2.65 ± 0.28; P = 0.07). The uni- and multivariate analyses showed that POSTN-positive expression (hazard ratio [HR], 1.595; 95% confidence interval [CI], 0.770-3.031; P = 0.03), CAR (HR, 1.663; 95% CI, 1.016-2.764; P = 0.03), gender (HR, 2.303; 95% CI, 1.067-6.019; P = 0.03), and tumor depth (HR, 1.957; 95% CI, 1.122-3.526; P = 0.01) were independent prognostic factors. CONCLUSIONS: Because POSTN-positive expression strongly correlates with immunoinflammatory measures, especially PLR and CAR, it is an independent prognostic factor in ESCC.

Impact of postoperative infectious complications on adjuvant chemotherapy administration after gastrectomy for advanced gastric cancer.

BACKGROUND: The aim of this study was to investigate the impact of postoperative infectious complications on adjuvant chemotherapy administration in patients with gastric cancer. METHODS: A retrospective review of 308 patients who underwent curative resection for gastric cancer was performed. Patients were divided into two groups based on the presence (90 patients, 29.2%) or absence (218 patients, 70.8%) of postoperative infectious complications to analyze clinicopathological characteristics, treatment factors and survival. RESULTS: Fewer patients with postoperative infectious complication received adjuvant chemotherapy compared to those without postoperative infectious complication. The proportion of patients who started treatment within 6 weeks after surgery was significantly lower in patients with postoperative infectious complication. The treatment completion rate was significantly lower in patients with postoperative infectious complication. The number of treatment cycles and relative dose intensity was significantly lower in patients with postoperative infectious complication. In univariate analysis, only postoperative infectious complication was significantly associated with continuation of adjuvant chemotherapy. Multivariate analysis demonstrated tumor depth, nodal involvement, postoperative infectious complication and adjuvant chemotherapy were significantly associated with overall survival. CONCLUSION: Postoperative infectious complications are significantly associated with the delay of adjuvant chemotherapy and predict adverse clinical outcome in patients with gastric cancer.

Clinical Significance of Programmed Death Ligand-1 Expression in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The aim of this study was to evaluate the association between the expression of programmed death ligand-1 (PD-L1) and clinical outcomes in patients with surgically resected esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We included 76 patients with primary ESCC who underwent surgical resection between January 2009 and December 2014 at National Defense Medical College Hospital. Using the tumor tissues, we evaluated PD-L1 expression in tumor cells and stromal reactive lymphocytes via immunohistochemistry. Furthermore, the relationship between PD-L1 expression and the clinicopathological status of patients with ESCC was investigated. RESULTS: PD-L1 expression in tumor cells was detected in 39.5% of the patients. In addition, 51.3% of the patients had PD-L1-positive stromal reactive lymphocytes and exhibited significantly longer overall survival than those with lack of PD-L1 expression in stromal reactive lymphocytes (median survival time, 56.0 versus 27.3 mo; log-rank test, P = 0.04). Patients with lack of PD-L1 expression in both tumor cells and stromal reactive lymphocytes showed worse overall survival than those with the PD-L1-positive expression in tumor cells and/or stromal reactive lymphocytes (P = 0.02). CONCLUSIONS: PD-L1-positive expression in stromal reactive lymphocytes, rather than in tumor cells, is associated with a longer survival in patients with ESCC.

Risk factors for nonalcoholic fatty liver disease after gastrectomy for gastric cancer.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to hepatic steatosis caused by something other than alcoholic liver injury, and often occurs after gastrointestinal surgeries such as pancreatoduodenectomy and gastrectomy. This study aimed to identify the risk factors for NAFLD after gastrectomy for gastric cancer. METHODS: A total of 721 patients who underwent gastrectomy for gastric cancer and plane abdominal computed tomography (CT) preoperatively and 1 year after surgery were included in this study. NAFLD was defined as having a mean hepatic CT attenuation value of < 40 Hounsfield units. We retrospectively examined the relationship between the onset of NAFLD and clinicopathological findings to identify the risk factors associated with the development of NAFLD after gastrectomy. RESULTS: The incidence of postoperative NAFLD was 4.85% (35/721). The univariate analysis identified the following factors as being significantly associated with the incidence of NAFLD: age, preoperative BMI ≥ 25 kg/m2, tumor depth of pT3 ≤, lymph node metastasis grade of pN2 ≤, cholecystectomy, D2 lymphadenectomy, adjuvant chemotherapy, high preoperative cholinesterase serum level, and low grade of preoperative FIB-4 index. Adjuvant chemotherapy (p < 0.001) and high preoperative cholinesterase serum level (p = 0.021) were identified as independent risk factors for NAFLD 1 year after gastrectomy. CONCLUSION: Our study showed that adjuvant chemotherapy with S-1 and high level of serum cholinesterase were considered as the risk factors for NAFLD occurring after gastrectomy for gastric cancer.

Impact of perioperative high mobility group box chromosomal protein 1 expression on long-term outcomes in patients with esophageal squamous cell carcinoma.

BACKGROUND AND AIM: High mobility group box chromosomal protein-1 (HMGB-1) is a potential late mediator of sepsis and a possible risk factor for postoperative pulmonary complications after esophagectomy. This study aimed to determine the relationship between HMGB-1 and clinicopathological factors and long-term prognosis after esophagectomy for esophageal cancer. METHODS: We measured perioperative serum HMGB-1 levels using ELISA and HMGB-1 protein by immunohistochemistry expression in resected specimens. RESULTS: Postoperative serum HMGB-1 levels were significantly higher than preoperative levels. Preoperative serum HMGB-1 levels were significantly higher in patients with more intraoperative bleeding, longer intensive care unit stays, and postoperative pneumonia. Postoperative serum HMGB-1 levels were significantly higher in older patients and those with longer operation time and more intraoperative bleeding. There were significant differences in long-term outcomes according to postoperative but not preoperative serum HMGB-1 levels. Multivariate analysis demonstrated that advanced pathological stage, postoperative pulmonary complications, and higher postoperative serum HMGB-1 levels were independently associated with relapse-free survival and overall survival. Preoperative serum HMGB-1 levels were significantly higher in patients with high HMGB-1 expression than those with low HMGB-1 expression by immunohistochemistry, whereas such statistical differences were not observed in postoperative serum HMGB-1. There were no differences in relapse-free survival and overall survival according to HMGB-1 expression by immunohistochemistry. Serum HMGB-1 levels were significantly increased after esophagectomy for esophageal cancer. CONCLUSION: Elevated postoperative serum HMGB-1, which was associated not only with poor long-term but also short-term outcomes such as postoperative complications, might serve as a potential marker for prognosis in esophageal cancer.

Efficacy of artificial pneumothorax under two-lung ventilation in video-assisted thoracoscopic surgery for esophageal cancer.

BACKGROUND: One-lung ventilation (OLV) is the standard and widely applied ventilation approach used in video-assisted thoracoscopic surgery for esophageal cancer (VATS-e). To address the disadvantages of OLV with respect to difficulties in intubation and induction, as well as the risk of respiratory complications, two-lung ventilation (TLV) with artificial pneumothorax has been introduced for use in VATS-e. However, no studies have yet compared TLV and OLV with postoperative infection and inflammation in the prone position over time postoperatively. Here, we investigated the efficacy of TLV in patients undergoing VATS-e in the prone position. METHODS: Between April 2010 and December 2016, 119 patients underwent VATS-e under OLV or TLV with carbon dioxide insufflation. Clinical characteristics, surgical outcomes, and postoperative outcomes, including oxygenation and systemic inflammatory responses, were compared between patients who underwent OLV and those who underwent TLV. RESULTS: Clinical characteristics other than pT stage were comparable between groups. The TLV group had shorter thoracic operation time than the OLV group. No patients underwent conversion to open thoracotomy. The PaO2/FiO2 ratios of the TLV group on postoperative day (POD) 5 and on POD7 were significantly higher than those of the OLV group. C-reactive protein levels on POD7 were lower in the TLV group than in the OLV group. There were no significant differences with respect to postoperative complications between the OLV and TLV groups. In the TLV group, the white blood cell count on POD7 was significantly lower than that in the OLV group; body temperature showed a similar trend immediately after surgery and on POD1. CONCLUSIONS: In this study, we demonstrated that, compared with OLV, TLV in the prone position provides better oxygenation and reduced inflammation in the postoperative course. Accordingly, TLV might be more useful than OLV for ventilation during esophageal cancer surgery.

Bilateral Approach for Thoracoscopic Esophagectomy in a Patient with Esophageal Cancer and Solitary Posterior Thoracic Para-aortic Lymph Node Metastasis.

We report a successful dissection of metastatic posterior thoracic para-aortic lymph node (No. 112aoP) via bilateral thoracoscopic surgery. With the anesthetized patient (a 73-year-old Japanese woman) in the prone position, two working ports were inserted for the left-side approach, and artificial pneumothorax was created. Thoracoscopic examination revealed a swollen LN posterior to the descending aorta. Fat and metastatic LNs posterior to the aorta were dissected from the aortic arch level to the diaphragm while preserving intercostal arteries. For the right-side approach, two working ports were inserted and a routine thoracoscopic esophagec-tomy was performed. Gastric conduit reconstruction was achieved laparoscopically. Operation time for the left thoracic procedure: 54 min; estimated blood loss: almost none. No recurrence was detected 24 months post-operatively. There are several surgical options for approaching No. 112aoP, including transhiatal, left thora-cotomy, and thoracoscopy. Although a wide dissection of the posterior thoracic para-aortic area has not been reported, it may be feasible and safe if the artery of Adamkiewicz and intercostal arteries are preserved. A min-imally invasive bilateral thoracoscopic approach for a thoracoscopic esophagectomy is safe and useful for esophageal cancer patients with solitary No. 112aoP metastasis.

A novel type of prolactin expressed in the bullfrog pituitary specifically during the larval period.

Prolactin (PRL) is one of the major hormones that control amphibian metamorphosis. Recently, a PRL (PRL1B) gene that is different from the known PRL (PRL1A) gene has been found in the genomes of several amphibian species. In order to ascertain whether the PRL1B gene is expressed in the bullfrog (Rana catesbeiana) pituitary, cloning of cDNA encoding PRL1B in the pituitary of the premetamorphic bullfrog tadpole was attempted. The bullfrog PRL1B amino acid sequence predicted from the obtained cDNA showed 62% identity with those of Xenopus PRL1Bs that have been presumed from the genome sequences, whereas the sequence identity between bullfrog PRL1A and PRL1B was 48%. A molecular phylogenetic tree showed that bullfrog PRL1B is most appropriately grouped with amphibian PRL1Bs. Quantitative PCR analysis revealed that the mRNA expression levels of bullfrog PRL1B in the pituitary were high during pre- and prometamorphosis, sharply declined at metamorphic climax and became undetectable after metamorphosis. In contrast, PRL1A mRNA levels were relatively low during pre- and prometamorphosis, rose at climax and remained high after metamorphosis. Immunohistochemical study using antibodies against partial peptides of PRL1A and PRL1B revealed that most of the PRL1A- and PRL1B-immunoreactive cells in the larval pituitary were distributed separately, but that some of the cells immunoreactive with both antibodies were also present. Western blot analysis with the larval pituitary extract indicated that PRL1B-immunoreactive band appeared at the position of molecular weight ca. 22.1 kDa and PRL1A-immunoreactive band at the position of ca. 22.8 kDa. The results obtained in this experiment suggest the possibility that PRL1B plays as-yet-unknown role(s) during the pre-climactic period of metamorphosis. This is the first report on the existence of PRL1B as a protein in the amphibian larval pituitary.

Prognostic Value of Preoperative Systemic Immunoinflammatory Measures in Patients with Esophageal Cancer.

BACKGROUND: It is reported that several systemic immunoinflammatory measures, including systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and C-reactive protein (CRP)-to-albumin ratio (CAR), are associated with survival in patients with various types of cancer. OBJECTIVE: The aim of the present study was to clear which systemic immunoinflammatory measures had the greatest prognostic values. In addition, we examined which component had the greatest prognostic power in patients with esophageal cancer. METHODS: Preoperative systemic immunoinflammatory measures were evaluated in 143 patients undergoing esophageal resection for esophageal cancer from 2009 to 2014. Univariate and multivariate analyses were performed to determine the prognostic significance of these markers. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curves (AUROCs) were compared to verify the accuracy of each measure in predicting overall survival (OS). RESULTS: In univariate analysis, preoperative SII, NLR, and CAR were the predictors of OS in patients who underwent esophagectomy for esophageal cancer (p < 0.05, respectively), whereas in multivariate analysis, CAR and pathological tumor depth were the significant predictors of OS (hazard ratio [HR] 1.994, p = 0.03 vs. HR 1.967, p = 0.02, respectively). According to AUROC, the CRP (0.66) and albumin levels (0.66) were more important systemic immunoinflammatory measures than neutrophil (0.58), lymphocyte (0.63), and platelet (0.56) levels. CONCLUSION: Among systemic immunoinflammatory measures, CAR was the most significant predictor of OS in patients with esophageal cancer. CRP and albumin levels were more important components of systemic immunoinflammatory measures.

Tetanus in a partially immunized child.

A 13-year-old boy developed tetanus, although he had protective antitoxin antibody raised by three doses of tetanus toxoid vaccine. Four days after injury, he presented with muscle rigidity of his posterior neck, excessive diaphoresis, and risus sardonicus and was subsequently diagnosed with tetanus. Tetanus is rare in developed countries, particularly during childhood, but must be promptly diagnosed based on clinical symptoms.

MET4 expression predicts poor prognosis of gastric cancers with Helicobacter pylori infection.

The role of HGF/SF-MET signaling is important in cancer progression, but its relation with Helicobacter pylori-positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti-HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of MET-staining status with outcome. The effect of live H. pylori bacteria on cell signaling and biological behaviors was evaluated using gastric cancer cell lines. MET4-positive gastric cancers showed poorer prognosis than MET4-negative cases (overall survival, P = 0.02; relapse-free survival, P = 0.06). Positive staining for MET4 was also a statistically significant factor to predict poor prognosis in H. pylori-positive cases (overall survival, P < 0.01; relapse-free survival, P = 0.01) but not in H. pylori-negative cases. Gastric cancers positively stained with both HGF/SF and MET4 showed a tendency of the worst prognosis. Stimulation of MET-positive gastric cancer cells with live H. pylori bacteria directly upregulated MET phosphorylation and activated MET downstream signals such as p44/42MAPK and Akt, conferring cell proliferation and anti-apoptotic activity. In conclusion, positive staining for MET4 was useful for predicting poor prognosis of gastric cancers with H. pylori infection. Helicobacter pylori stimulated MET-positive gastric cancers and activated downstream signaling, thereby promoting cancer proliferation and anti-apoptotic activity. These results support the importance of H. pylori elimination from gastric epithelial surface in clinical therapy.

Respiratory Uptake and Depuration Kinetics of Perfluorooctanesulfonate (PFOS) in a Marine Sandworm Species.

We determined the respiratory uptake and depuration kinetics of perfluorooctanesulfonate (PFOS) in Perinereis wilsoni, a polychaete sandworm used as a model species to investigate the fate of chemical pollutants in coastal environments. The sandworms were kept in gravel-packed containers, and the water levels were varied cyclically to mimic the tides. We used seawater kept at 17.1°C. A 7-day exposure period was followed by a 9-day depuration period. The dissolved PFOS concentration averaged 28 ng/L during the exposure period. Sandworm samples were collected regularly for analysis of PFOS concentrations, and a first-order-kinetics model was applied to the concentrations. The respiratory absorption efficiency of PFOS was estimated to be 11% that of oxygen, which is higher than the corresponding estimates reported for several fish species. The estimated depuration half-life of 15 days was comparable to previously reported estimates for fish and oligochaete species. The bioconcentration factor was 470.

In vivo evaluation of a modified linear stapling device designed to facilitate accurate pathologic examination of the surgical margin.

BACKGROUND: Microscopic involvement of the resection margin could influence the long-term outcome of patients undergoing curative surgery for gastric cancer. Linear staplers, commonly used for gastrectomies, are often equipped with three lines of staples on either side of the resection line. Although multiple lines of staples reinforce closure of the gastric or intestinal stump, they could hinder accurate histopathologic evaluation of the surgical margin of the resected specimen. METHODS: We modified a linear stapling device by removing one line (stapler E2) or two lines (stapler E1) of staples on the specimen side, and attempted to dissect a silicon film and then the stomach from a porcine model using the stapling device and examined the distances between the cutting edge and the nearest staple line. RESULTS: The distance between the cutting edge and the staple line for stapler E1 was significantly greater than the distance between the cutting edge and the nearest staple line for stapler E2 or the control device. Consequently, specimens of exemplary quality were available for pathologic examination of the surgical margin. Moreover, the lack of multiple layers of staples did not result in contamination of the abdominal cavity with gastric juice during laparoscopic procedures in the porcine model. CONCLUSIONS: Stapler E1 is safe and could be useful for the pathologic evaluation of the true surgical margin.

Influence of hepatic load from far-off dry period to early postpartum period on the first postpartum ovulation and accompanying subsequent fertility in dairy cows.

The aim of the present study was to investigate nutritional and metabolic parameters during the dry and early postpartum periods of ovulatory and anovulatory cows, as well as their postpartum reproductive performance. Blood samples from 20 multiparous Holstein cows were collected once a week from the far-off dry period to 3 weeks postpartum. Early postpartum (0-3 weeks) ovulation was confirmed using plasma progesterone concentration profiles, and cows were considered ovulatory if they had resumed luteal activity by this point (n = 9), whereas cows that had not were considered anovulatory (n = 11). Data from the ovulatory and anovulatory cows were analyzed separately for the far-off dry period (7-4 weeks prepartum), the close-up dry period (3-1 weeks prepartum), and the early postpartum period (0-3 weeks). Serum gamma-glutamyl transpeptidase activity (far-off, P = 0.065; close-up, P = 0.051; and early postpartum, P = 0.030) and aspartate aminotransferase (close-up, P = 0.050 and early postpartum, P = 0.087) activities were higher in anovulatory than in ovulatory cows. The days open period was longer (P = 0.019) in anovulatory than in ovulatory cows, and the number of artificial inseminations per conception (P = 0.025) was greater. In conclusion, we found that continuously high gamma-glutamyl transpeptidase activities in serum, which may be induced by liver disorders, prevent subsequent ovulation and affect subsequent fertility, even if cows obtain sufficient ovulation-related energy and ß-carotene.

Pivotal role of myeloid-derived suppressor cells in infection-related tumor growth.

BACKGROUND: In this study, we investigated infection-related tumor growth, focusing on myeloid-derived suppressor cells (MDSCs) in clinical and experimental settings. PATIENTS AND METHODS: In the clinical study, a total 109 patients who underwent gastrectomy or esophagectomy were included. Blood samples were collected from a preoperative time point through 3 months after surgery, and MDSCs were analyzed using flow cytometry. In animal experiments, peritonitis model mice were created by CLP method. We investigated the number of splenic MDSCs in these mice using flow cytometry. Malignant melanoma cells (B16F10) were inoculated on the back of the mice, and tumor growth was monitored. We compared the level of MDSC infiltration around the tumor and the migration ability between CLP and sham-operated mice-derived MDSCs. Finally, we focused on PD-L1+ MDSCs to examine the effectiveness of anti-PD-L1 antibodies on tumor growth in CLP mice. RESULTS: In patients with postoperative infectious complication, MDSC number was found to remain elevated 3 months after surgery, when the inflammatory responses were normalized. CLP mice showed increased numbers of MDSCs, and following inoculation with B16F10 cells, this higher number of MDSCs was associated with significant tumor growth. CLP-mice-derived MDSCs had higher levels of accumulation around the tumor and had more enhanced migration ability. Finally, CLP mice had increased numbers of PD-L1+ MDSCs and showed more effective inhibition of tumor growth by anti-PD-L1 antibodies compared to sham-operated mice. CONCLUSION: Long-lasting enhanced MDSCs associated with infection may contribute to infection-related tumor progression.

Design of a gold clustering site in an engineered apo-ferritin cage.

Water-soluble and biocompatible protein-protected gold nanoclusters (Au NCs) hold great promise for numerous applications. However, design and precise regulation of their structure at an atomic level remain challenging. Herein, we have engineered and constructed a gold clustering site at the 4-fold symmetric axis channel of the apo-ferritin cage. Using a series of X-ray crystal structures, we evaluated the stepwise accumulation process of Au ions into the cage and the formation of a multinuclear Au cluster in our designed cavity. We also disclosed the role of key residues in the metal accumulation process. X-ray crystal structures in combination with quantum chemical (QC) calculation revealed a unique Au clustering site with up to 12 Au atoms positions in the cavity. Moreover, the structure of the gold nanocluster was precisely tuned by the dosage of the Au precursor. As the gold concentration increases, the number of Au atoms position at the clustering site increases from 8 to 12, and a structural rearrangement was observed at a higher Au concentration. Furthermore, the binding affinity order of the four Au binding sites on apo-ferritin was unveiled with a stepwise increase of Au precursor concentration.