Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.

Using the geriatric nutritional risk index to predict outcomes in older patients with remnant gastric cancer after gastrectomy: a retrospective multicenter study in Japan.

PURPOSE: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC). METHODS: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS. CONCLUSIONS: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC.

An Autotaxin-Induced Ocular Hypertension Mouse Model Reflecting Physiological Aqueous Biomarker.

Purpose: Animal models of ocular hypertension (OH) have been developed to understand the pathogenesis of glaucoma and facilitate drug discovery. However, many of these models are fraught with issues, including severe intraocular inflammation and technical challenges. Lysophosphatidic acid (LPA) is implicated in trabecular meshwork fibrosis and increased resistance of aqueous outflow, factors that contribute to high intraocular pressure (IOP) in human open-angle glaucoma. We aimed to elevate IOP by increasing expression of the LPA-producing enzyme autotaxin (ATX) in mouse eyes. Methods: Tamoxifen-inducible ATX transgenic mice were developed. Tamoxifen was administered to six- to eight-week-old mice via eye drops to achieve ATX overexpression in the eye. IOP and retinal thickness were measured over time, and retinal flat-mount were evaluated to count retinal ganglion cells (RGCs) loss after three months. Results: Persistent elevation of ATX expression in mouse eyes was confirmed through immunohistochemistry and LysoPLD activity measurement. ATX Tg mice exhibited significantly increased IOP for nearly two months following tamoxifen treatment, with no anterior segment changes or inflammation. Immunohistochemical analysis revealed enhanced expression of extracellular matrix near the angle after two weeks and three months of ATX induction. This correlated with reduced outflow facility, indicating that sustained ATX overexpression induces angle fibrosis, elevating IOP. Although inner retinal layer thickness remained stable, peripheral retina showed a notable reduction in RGC cell count. Conclusions: These findings confirm the successful creation of an open-angle OH mouse model, in which ATX expression in the eye prompts fibrosis near the angle and maintains elevated IOP over extended periods.

Preoperative low skeletal muscle volume can result in insufficient administration of S-1 adjuvant chemotherapy in older patients with stage II/III gastric cancer.

BACKGROUND AND PURPOSE: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. METHODS: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. RESULTS: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). CONCLUSION: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.

A gastroduodenal artery that branched from the celiac artery in gastrectomy: A rare case of an anatomical variant.

Understanding anatomical anomalies of the branch of the celiac artery for safe gastrectomy is important. We report a case of laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer with a vascular anatomical anomaly of the celiac artery. A 45-year-old woman was referred to our hospital because of early gastric cancer. Computed tomography showed an anatomical variation of the gastroduodenal artery, which branched from the celiac artery. The celiac artery also branched into the left gastric artery, the splenic artery, and the common hepatic artery. Preoperative understanding of an unusual branch of the celiac artery enabled a safe laparoscopic surgery. There were no postoperative complications. The Adachi classification or Michel classification is used for an anatomical anomaly of the celiac artery, but to the best of our knowledge, this case has not been previously classified and is the first reported case.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

Skeletal Muscle Mass Before Second-line Chemotherapy Correlates With Subsequent Prognosis and Rate of Late-line Chemotherapy in Patients With Unresectable Gastric Cancer.

BACKGROUND/AIM: Chemotherapy is the standard treatment for patients with unresectable gastric cancer (UGC); however, the survival outcomes are poor. This study investigated the predictive values of skeletal muscle mass (SMM) index (SMI) before second-line chemotherapy and the survival outcomes of patients with UGC. PATIENTS AND METHODS: A total of 79 patients diagnosed with UGC at our hospital who received at least second-line palliative chemotherapy were included. The cross-sectional SMM at the third lumbar vertebra was obtained before second-line chemotherapy. SMI was defined as the muscle area normalized by height squared (m2), and SMI before second-line chemotherapy was defined as 2ndSMI. RESULTS: Using 2ndSMI for men and women (35.4 and 31.7 cm2/m2, respectively) as the cutoff value, patients were divided into high (2ndSMIHigh; n=54) and low (2ndSMILow; n=25) 2ndSMI groups. The number of patients receiving fourth-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.039). The overall survival time after the start of second-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.008). The incidence of grade 3 or 4 side effects was significantly higher in the 2ndSMILow than in the 2ndSMIHigh group (p=0.028). The multivariate analysis identified 2ndSMI as independent prognostic factor after the start of second-line chemotherapy. CONCLUSION: The 2ndSMILow group had a significantly worse prognosis and significantly less conversion to fourth-line chemotherapy than the 2ndSMIHigh group. Moreover, 2ndSMILow was associated with grade 3 or 4 side effects of second-line chemotherapy.

Preoperative Osteopenia as Risk Factor for Death from Other Diseases After Gastrectomy in Elderly Patients.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density, is a prognostic factor in patients with digestive tract cancers, including gastric cancer (GC). However, the correlation between preoperative osteopenia and GC in elderly patients is unclear. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. Patients were classified into the non-elderly group (n=169) and the elderly group (n=82). Bone mineral density was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Although overall survival was significantly shorter in the elderly compared to the non-elderly group (p=0.0062), there was no significant difference in disease-specific survival between the two groups (p=0.71) because of the higher rate of death from other diseases. In addition, the elderly group had a significantly higher incidence of osteopenia (p<0.001) and a significantly lower prognostic nutritional index (p<0.001). Multivariate analysis revealed that preoperative osteopenia and a low preoperative prognostic nutritional index were significant risk factors for death from other diseases after gastrectomy in elderly patients. CONCLUSION: In elderly patients with GC, preoperative osteopenia is an important factor to consider in terms of both curability and death from other diseases.

Using singular value decomposition to analyze drug/ß-cyclodextrin mixtures: insights from X-ray powder diffraction patterns.

The article discusses the use of mathematical models and linear algebra to understand the crystalline structures and interconversion pathways of drug complexes with ß-cyclodextrin (ß-CD). It involved the preparation and analysis of mixtures of indomethacin, diclofenac, famotidine, and cimetidine with ß-CD using techniques such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and proton nuclear magnetic resonance (1H-NMR). Singular value decomposition (SVD) analysis is used to identify the presence of different polymorphs in the mixtures of these drugs and ß-CD, determine interconversion pathways, and distinguish between different forms. In general, linear algebra or artificial intelligence (AI) is used to approximate the contribution of distinguishable entities to various phenomena. We expected linear algebra to completely reveal all eight entities present in the diffractogram dataset. However, after performing the SVD procedure, we found that only six independent basis functions were extracted, and the entities of the INM α-form and the CIM B-form were not included. It is considered that this is due to that data processing is limited to revealing only six or seven independent factors, as it is a small world. The authors caution that these may not always reproduce or approach reality in complicated real-world situations.

Aging impairs the ability of vascular endothelial stem cells to generate endothelial cells in mice.

Tissue-resident vascular endothelial stem cells (VESCs), marked by expression of CD157, possess long-term repopulating potential and contribute to vascular regeneration and homeostasis in mice. Stem cell exhaustion is regarded as one of the hallmarks of aging and is being extensively studied in several types of tissue-resident stem cells; however, how aging affects VESCs has not been clarified yet. In the present study, we isolated VESCs from young and aged mice to compare their potential to differentiate into endothelial cells in vitro and in vivo. Here, we report that the number of liver endothelial cells (ECs) including VESCs was lower in aged (27-28 month-old) than young (2-3 month-old) mice. In vitro culture of primary VESCs revealed that the potential to generate ECs is impaired in aged VESCs isolated from liver and lung relative to young VESCs. Orthotopic transplantation of VESCs showed that aged VESCs and their progeny expand less efficiently than their young counterparts when transplanted into aged mice, but they are equally functional in young recipients. Gene expression analysis indicated that inflammatory signaling was more activated in aged ECs including VESCs. Using single-cell RNA sequencing data from the Tabula Muris Consortium, we show that T cells and monocyte/macrophage lineage cells including Kupffer cells are enriched in the aged liver. These immune cells produce IL-1ß and several chemokines, suggesting the possible involvement of age-associated inflammation in the functional decline of VESCs with age.

Single-cell sequencing reveals the existence of fetal vascular endothelial stem cell-like cells in mouse liver.

BACKGROUND: A resident vascular endothelial stem cell (VESC) population expressing CD157 and CD200 has been identified recently in the adult mouse. However, the origin of this population and how it develops has not been characterized, nor has it been determined whether VESC-like cells are present during the perinatal period. Here, we investigated the presence of perinatal VESC-like cells and their relationship with the adult VESC-like cell population. METHODS: We applied single-cell RNA sequencing of endothelial cells (ECs) from embryonic day (E) 14, E18, postnatal day (P) 7, P14, and week (W) 8 liver and investigated transcriptomic changes during liver EC development. We performed flow cytometry, immunofluorescence, colony formation assays, and transplantation assays to validate the presence of and to assess the function of CD157+ and CD200+ ECs in the perinatal period. RESULTS: We identified CD200- expressing VESC-like cells in the perinatal period. These cells formed colonies in vitro and had high proliferative ability. The RNA velocity tool and transplantation assay results indicated that the projected fate of this population was toward adult VESC-like cells expressing CD157 and CD200 1 week after birth. CONCLUSION: Our study provides a comprehensive atlas of liver EC development and documents VESC-like cell lineage commitment at single-cell resolution.

Preoperative Osteopenia Is a Risk Factor for Death in Patients Undergoing Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density (BMD), has been reported as a prognostic factor in patients with digestive tract cancers. However, the correlation between preoperative osteopenia and the prognosis of gastric cancer (GC) remains unclear. The aim of this study was to reveal the importance of preoperative osteopenia as a prognostic factor in patients undergoing gastrectomy for GC. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. BMD was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Osteopenia had a high area under the curve and predictive value for both overall survival (OS) and disease-specific survival (DSS). The study cohort was categorized into an osteopenia group and non-osteopenia group based on the optimal BMD cutoff values for OS (157.5) and DSS (195) determined by receiver operating characteristic analysis. The multivariate analysis revealed that OS (hazard ratio=3.607, p<0.001) and DSS (hazard ratio=2.797, p=0.03) were significantly worse in patients with than without preoperative osteopenia. CONCLUSION: Preoperative osteopenia is associated with poor OS and DSS in patients undergoing gastrectomy for GC.

Tight association of CpcL with photosystem I in Anabaena sp. PCC 7120 grown under iron-deficient conditions.

Phycobilisomes (PBSs), which are huge pigment-protein complexes displaying distinctive color variations, bind to photosystem cores for excitation-energy transfer. It is known that isolation of supercomplexes consisting of PBSs and photosystem I (PSI) or PBSs and photosystem II is challenging due to weak interactions between PBSs and the photosystem cores. In this study, we succeeded in purifying PSI-monomer-PBS and PSI-dimer-PBS supercomplexes from the cyanobacterium Anabaena sp. PCC 7120 grown under iron-deficient conditions by anion-exchange chromatography, followed by trehalose density gradient centrifugation. The absorption spectra of the two types of supercomplexes showed apparent bands originating from PBSs, and their fluorescence-emission spectra exhibited characteristic peaks of PBSs. Two-dimensional blue-native (BN)/SDS-PAGE of the two samples showed a band of CpcL, which is a linker protein of PBS, in addition to PsaA/B. Since interactions of PBSs with PSI are easily dissociated during BN-PAGE using thylakoids from this cyanobacterium grown under iron-replete conditions, it is suggested that iron deficiency for Anabaena induces tight association of CpcL with PSI, resulting in the formation of PSI-monomer-PBS and PSI-dimer-PBS supercomplexes. Based on these findings, we discuss interactions of PBSs with PSI in Anabaena.

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen.

Perioperative Infusion Management for Adhesive Bowel Obstruction with Congenital Nephrogenic Diabetes Insipidus: A Case Report.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disease that results in polyuria due to decreased responsiveness to the antidiuretic hormone in the collecting ducts of the kidney. Without compensation by drinking large amounts of water, dehydration and hypernatremia can rapidly develop. We present a case of a patient originally diagnosed with CNDI who required surgery and a fasting period due to adhesive bowel obstruction. The patient was a 46-year-old man who was originally diagnosed with CNDI. He was prescribed trichlormethiazide but self-discontinued treatment in the process. His normal urine output was about 7,000-8,000 mL/day. He underwent robot-assisted radical cystectomy and uretero-cutaneostomy for bladder cancer. Two years later, he was hospitalized due to adhesive bowel obstruction. A 5% glucose solution was infused, and the dose was adjusted according to the urine volume and electrolytes. An adhesiotomy was performed due to recurrent bowel obstruction in a short period of time. A 5% glucose solution was used as the main infusion during the perioperative period. Once drinking water was resumed after surgery, urinary output and electrolytes were easily controlled. In conclusion, patients with CNDI should be given a 5% glucose solution as the primary infusion, and the infusion volume should be adjusted by monitoring daily urine output, electrolytes, and blood glucose levels. Infusion management is easier if oral intake is initiated as early as possible.

Impact of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Short-Term Analysis.

Background: We compared short-term clinical outcomes between robotic-assisted minimally invasive esophagectomy (RAMIE) and video-assisted thoracic esophagectomy (VATS-E) using propensity score-matched analysis. Methods: We enrolled 114 patients with esophageal cancer who underwent esophagectomy at our institution from January 2013 to January 2022. Propensity score matching was performed to minimize selection bias between the RAMIE and VATS-E groups. Results: After propensity score matching, 72 patients (RAMIE group, n = 36; VATS-E group, n = 36) were selected for analysis. No significant differences in clinical variables were observed between the two groups. The RAMIE group had a significantly longer thoracic operation time (313 ± 40 vs. 295 ± 35 min, P = 0.048), a higher number of right recurrent laryngeal nerve lymph nodes (4.2 ± 2.7 vs. 2.9 ± 1.9, P = 0.039), and a shorter postoperative hospital stay (23.2 ± 12.8 vs. 30.4 ± 18.6 days, P = 0.018) than the VATS-E group. The RAMIE group tended to have a lower rate of anastomotic leakage (13.9% vs. 30.6%) than the VATS-E group, although the difference was not statistically significant (P = 0.089). No significant differences were found in recurrent laryngeal nerve paralysis (11.1% vs. 13.9%, P = 0.722) or pneumonia (13.9% vs. 13.9%, P = 1.000) between the RAMIE group and the VATS-E group. Conclusion: Although RAMIE for esophageal cancer requires a longer thoracic surgery time, it might be a feasible and safe alternative to VATS-E for treating esophageal cancer. Further analysis is needed to clarify the advantages of RAMIE over VATS-E, especially in terms of long-term surgical outcomes.

A low cumulative perioperative prognostic nutritional index predicts poor long-term outcomes in patients with gastric cancer: A single-center retrospective study in Japan.

PURPOSE: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC). METHODS: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method. RESULTS: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC. CONCLUSIONS: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC.

Right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes after esophagectomy.

Mediastinal lymph node recurrence is often observed following esophageal cancer surgery; however, no treatment has been established for the same. Surgical resection is often considered for cases of recurrence in a single lymph node region, although the procedures and approaches vary depending on the recurrence site. Right thoracoscopic resection is rarely opted for owing to its high surgical difficulty. Herein, we report a successful case of right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes following esophagectomy. The intraoperative findings revealed few adhesions around the recurrent lymph nodes due to the initial surgery, and the recurrent lymph nodes were safely resected within a short period. The patient was discharged on postoperative day 4 without any complications, and there was no recurrence after 20 months. Thus, right thoracoscopic resection may be a promising treatment option for recurrent pretracheal lymph nodes after esophagectomy.

Usefulness of the Modified Frailty Index for Predicting Pneumonia Occurrence After Esophagectomy.

Background: Esophagectomy is an invasive and complication-prone surgical procedure. Therefore, a tool that can predict the occurrence of postoperative complications may be useful for perioperative management. In this study, we investigated whether the modified frailty index (mFI) could be a useful tool for predicting the postoperative complications of esophagectomy. Methods: In this study, 162 patients who underwent curative esophagectomy for esophageal squamous cell carcinoma from 2004 to 2019 at our institution were included. The patients were divided into the high mFI (≥ 0.27) and low mFI (< 0.27) groups, and the short-term postoperative outcomes of each group were examined retrospectively. Results: Regarding background factors, age and the American Society of Anesthesiologists physical status classification were significantly higher in the high mFI group (P = 0.049 and P = 0.002, respectively); however, the other items were not significantly different between the two groups. Regarding surgical outcomes, no significant differences in operative time, blood loss, and hospital stay were observed between the two groups. Regarding postoperative complications, pneumonia was significantly more common in the high mFI group (P = 0.035). In multivariate analysis, high mFI (P = 0.034) was an independent predictor of pneumonia, along with operative time ≥ 613 min (P = 0.03) and preoperative BMI < 20.48 (P = 0.006). Conclusion: The mFI is useful for predicting pneumonia after esophagectomy.

Structure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120.

Iron-stress-induced-A proteins (IsiAs) are expressed in cyanobacteria under iron-deficient conditions. The cyanobacterium Anabaena sp. PCC 7120 has four isiA genes; however, their binding property and functional roles in PSI are still missing. We analyzed a cryo-electron microscopy structure of a PSI-IsiA supercomplex isolated from Anabaena grown under an iron-deficient condition. The PSI-IsiA structure contains six IsiA subunits associated with the PsaA side of a PSI core monomer. Three of the six IsiA subunits were identified as IsiA1 and IsiA2. The PSI-IsiA structure lacks a PsaL subunit; instead, a C-terminal domain of IsiA2 occupies the position of PsaL, which inhibits the oligomerization of PSI, leading to the formation of a PSI monomer. Furthermore, excitation-energy transfer from IsiAs to PSI appeared with a time constant of 55 ps. These findings provide insights into both the molecular assembly of the Anabaena IsiA family and the functional roles of IsiAs.