Characterization of rice endosperm-derived antidepressant-like peptide (REAP): An orally active novel tridecapeptide derived from rice protein.

It is ideal to ingest bioactive substances from daily foods to stay healthy. Rice is the staple food for almost half of the human population. We found that an orally administered enzymatic digest of rice endosperm protein exhibits antidepressant-like effects in the tail suspension test (TST) using mice. A comprehensive peptide analysis of the digest using liquid chromatography-tandem mass spectrometry was performed, and a tridecapeptide QQFLPEGQSQSQK, detected in the digest, was chemosynthesized. Oral administration of the tridecapeptide exhibited antidepressant-like effects at a low dose comparable to classical antidepressant in the TST. This also exhibited anti-depressant-like effect in the forced swim test. We named it rice endosperm-derived antidepressant-like peptide (REAP). Intriguingly, intraperitoneal administration had no effect. Orally administered REAP(8-13) but not REAP(1-7) exhibited antidepressant-like activity, suggesting that the C-terminal structure is important for the antidepressant-like effect. We confirmed the presence of REAP, corresponding to rice glutelin type B4(130-142) and B5(130-142), in the digest. The effects of REAP were blocked by both dopamine D1 and D2 antagonists. These results suggest that it exerts its antidepressant-like activity through activation of the dopamine system. Taken together, oral administration of a novel tridecapeptide exhibited antidepressant-like effects via the dopamine system. This is the first report of a rice-derived peptide that exhibits antidepressant-like effects.

Current Status of Robotic Hepatobiliary and Pancreatic Surgery.

Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.

Successful prolonged treatment with sofosbuvir/velpatasvir for a hepatitis C patient with decompensated cirrhosis and treatment failure after 12-week therapy.

There is no established rescue therapy for hepatitis C patients with decompensated cirrhosis who experience treatment failure on 12-week sofosbuvir (SOF)/velpatasvir (VEL) therapy that is the only approved regimen for decompensated cirrhosis in Japan. We experienced a patient with decompensated cirrhosis who showed virologic relapse at post-treatment week 7 following 12-week SOF/VEL therapy. She had resistance-associated substitutions (RASs) against VEL before therapy but did not achieve new RASs against VEL or SOF after therapy. We considered rescue therapy following strong demand from her and her family. The drug adherence of therapy was 100%, and the treatment was well tolerated. Because we prioritized the safety and drug adherence of the regimen, we performed prolonged 24-week SOF/VEL therapy without ribavirin at her own expense with the approval of the ethics board in the hospital where the first author belongs. Fortunately, a sustained virologic response 24 was achieved without any adverse events. Hepatocellular carcinoma that had developed after 12-week SOF/VEL therapy recurred and was treated near the end of rescue therapy, but hepatic functional reserve improved. Although this was a single case report and was assumed to be very rare, the same regimen might be effective for treatment failure with 12-week SOF/VEL therapy.

Gallbladder strangulation caused by a fibrotic band due to chlamydia infection: A case report.

Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.

Current Status of Robotic Gastrointestinal Surgery.

Development of surgical support robots began in the 1980s as a navigation and auxiliary device for endoscopic surgery. For remote surgery on the battlefield, a master-slave-type surgical support robot was developed, in which a console surgeon operates the robot at will. The da Vinci surgical system, which currently dominates the global robotic surgery market, received United States Food and Drug Administration and regulatory approval in Japan in 2000 and 2009 respectively. The latest, fourth generation, da Vinci Xi has a good field of view via a three-dimensional monitor, highly operable forceps, a motion scale function, and a tremor-filtered articulated function. Gastroenterological tract robotic surgery is safe and minimally invasive when accessing and operating on the esophagus, stomach, colon, and rectum. The learning curve is said to be short, and robotic surgery will likely be standardized soon. Therefore, robotic surgery training should be systematized for young surgeons so that it can be further standardized and later adapted to a wider range of surgeries. This article reviews current trends and potential developments in robotic surgery.

Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management.

Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs.

Low-Rank Combinatorial Optimization and Statistical Learning by Spatial Photonic Ising Machine.

The spatial photonic Ising machine (SPIM) [13D. Pierangeli et al., Large-Scale Photonic Ising Machine by Spatial Light Modulation, Phys. Rev. Lett. 122, 213902 (2019).PRLTAO0031-900710.1103/PhysRevLett.122.213902] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. The primitive version of the SPIM, however, can accommodate Ising problems with only rank-one interaction matrices. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, it acquires the learning ability of Boltzmann machines. We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using the model with low-rank interactions. Thus, the proposed model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.

Spore-Forming Lactic Acid-Producing Bacterium Bacillus coagulans Synthesizes and Excretes Spermidine into the Extracellular Space.

The effect of spermidine in extending healthy longevity has attracted attention. As people age, their ability to synthesize putrescine, the precursor of spermidine, declines, and its supplementation from the diet or gut bacteria is needed. Many bacteria synthesize spermidine, but no strains have been reported to excrete de novo synthesized spermidine from the cells. We found that Bacillus coagulans strain YF1, isolated from "nanohana-duke", excreted de novo synthesized spermidine from the cells under anaerobic conditions. This strain synthesizes spermidine from arginine via agmatine, putrescine, and carboxyspermidine in sequential reactions, and the genes encoding the enzymes responsible for these reactions have been identified. B. coagulans is a gastric acid-resistant spore-forming lactic acid-producing bacterium, known for its beneficial effects as a probiotic. It can be used to produce lactic acid fermented foods containing spermidine. The newly discovered ability to excrete de novo synthesized spermidine is the decisive feature of this bacterium.

New insights into raceway cultivation of Euglena gracilis under long-term semi-continuous nitrogen starvation.

This study aimed to investigate the physiological responses of Euglena gracilis (E. gracilis) when subjected to semicontinuous N-starvation (N-) for an extended period in open ponds. The results indicated that the growth rates of E. gracilis under the N- condition (11 ± 3.3 g m-2 d-1) were higher by 23% compared to the N-sufficient (N+, 8.9 ± 2.8 g m-2 d-1) condition. Furthermore, the paramylon content of E.gracilis was above 40% (w/w) of dry biomass in N- condition compared to N+ (7%) condition. Interestingly, E. gracilis exhibited similar cell numbers regardless of nitrogen concentrations after a certain time point. Additionally, it demonstrated relatively smaller cell size over time, and unaffected photosynthetic apparatus under N- condition. These findings suggest that there is a tradeoff between cell growth and photosynthesis in E. gracilis, as it adapts to semi-continuous N- conditions without a decrease in its growth rate and paramylon productivity. Notably, to the author's knowledge, this is the only study reporting high biomass and product accumulation by a wild-type E. gracilis strain under N- conditions. This newly identified long-term adaptation ability of E. gracilis may offer a promising direction for the algal industry to achieve high productivity without relying on genetically modified organisms.

Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation.

Inflammatory bowel diseases (IBDs), such as Crohn's disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.

Investigation of the Effect of Students' Nodding on Their Arousal Levels in On-Demand Lectures.

Due to COVID-19, various lecture styles are being explored. On-demand lectures are attracting increasing attention due to advantages such as being able to watch without restrictions due to location and time. In contrast, on-demand lectures have disadvantages, such as no interaction with the lecturer, so the quality of on-demand lectures should be improved. Our previous study showed that when participants nod without showing their faces in a real-time remote lecture, their heart rate state changes to arousal and nodding can increase arousal. In this paper, we hypothesize that nodding during on-demand lectures increases participants' arousal levels, and we investigate the relationship between natural and forced nodding and the level of arousal based on heart rate information. Students taking on-demand lectures rarely nod naturally, so we used entrainment to encourage nodding by showing a video of another participant nodding, and by forcing the participants to nod when the other participant nodded in the video. The results showed that only participants who nodded spontaneously changed the value of pNN50, an index of the arousal level, which reflected a state of high arousal after one minute. Thus, participants' nodding in on-demand lectures can increase their arousal levels; however, the nodding must be spontaneous, not forced.

Research overview of L-DOPA production using a bacterial enzyme, tyrosine phenol-lyase.

L-DOPA is an amino acid that is used as a treatment for Parkinson's disease. A simple enzymatic synthesis method of L-DOPA had been developed using bacterial L-tyrosine phenol-lyase (Tpl). This review describes research on screening of bacterial strains, culture conditions, properties of the enzyme, reaction mechanism of the enzyme, and the reaction conditions for the production of L-DOPA. Furthermore, molecular bleeding of constitutively Tpl-overproducing strains is described, which were developed based on mutations in a DNA binding protein, TyrR, which controls the induction of tpl gene expression.

Immobilization of E. coli expressing γ-glutamyltranspeptidase on its surface for γ-glutamyl compound production.

An Escherichia coli strain expressing γ-glutamyltranspeptidase on its extracellular surface using the Met1 to Arg232 fragment of YiaT of E. coli as an anchor protein was immobilized with alginate for repeated use. Measurement of γ-glutamyltranspeptidase activity of the immobilized cells was performed repeatedly at pH 8.73 and 37 °C for 10 days using γ-glutamyl-p-nitroanilide in the presence of 100 mM CaCl2 and 3% NaCl with and without glycylglycine. Even after the 10th day, the enzyme activity did not decrease from the initial levels. The production of γ-glutamylglutamine from glutamine using the immobilized cells was performed repeatedly at pH 10.5 and 37 °C for 10 days in the presence of 250 mM glutamine, 100 mM CaCl2, and 3% NaCl. Sixty-four % of glutamine was converted to γ-glutamylglutamine in the first cycle. While repeating the production 10 times, the surface of the beads gradually became covered with white precipitate, and the conversion efficiency gradually decreased, but 72% of the initial value still remained even at the 10th measurement.

Diagnosis, Treatment, and Prevention of Ileostomy Complications: An Updated Review.

An ileostomy is associated with multiple complications that may frequently or persistently affect the life of ostomates. All healthcare professionals should have knowledge of the diagnosis, treatment, and prevention of ileostomy complications. Peristomal dermatitis is caused by watery and highly alkaline effluent. Skin protective products are typically used for local treatment. Ischemia/necrosis occurs due to insufficient arterial blood supply. Retraction is seen in patients with a bulky mesentery and occurs following ischemia. Convex stoma appliances can be used for skin protection against fecal leakage. Small bowel obstruction (SBO) is common and occurs only at the stoma site. Trans-stomal decompression is most effective in these cases. High output stoma (HOS) is defined as a condition when the output exceeds 1,000- 2,000 ml/day, lasting for one to three days. Treatment includes intravenous fluid and electrolyte resuscitation followed by restriction of hypotonic fluid and the use of antimotility (and antisecretory) drugs. Stomal prolapse is a full-thickness protrusion of an inverted bowel. Manual reduction is attempted initially, whereas emergency bowel resection may be needed for incarcerated cases. A parastomal hernia (PSH) is an incisional hernia of the stoma site. Surgery is considered in cases of incarceration, but most cases are manageable with non-surgical treatment.

Oncologic impact of colonic stents for obstructive left-sided colon cancer.

Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer (OLCC) in terms of both palliative treatment and bridge-to-surgery (BTS). Notably, many studies have convincingly demonstrated the effectiveness of stenting as a BTS, resulting in improvements in short-term outcomes and quality of life, safety, and efficacy in subsequent curative surgery, and increased cost-effectiveness, whereas the safety of chemotherapy after stenting and the long-term outcomes of stenting as a BTS are controversial. Several studies have suggested an increased risk of perforation in patients receiving bevacizumab chemotherapy after colonic stenting. In addition, several pathological analyses have suggested a negative oncological impact of colonic stenting. In contrast, many recent studies have demonstrated that colonic stenting for OLCC does not negatively impact the safety of chemotherapy or long-term oncological outcomes. The updated version of the European Society of Gastrointestinal Endoscopy guidelines released in 2020 included colonic stenting as a BTS for OLCC as a recommended treatment. It should be noted that the experience of endoscopists is involved in determining technical and clinical success rates and possibly oncological outcomes. This review discusses the positive and negative impacts of colonic stenting on OLCC treatment, particularly in terms of oncology.

First Example of the Extracellular Surface Expression of Intrinsically Periplasmic Escherichia coli γ-Glutamyltranspeptidase, a Member of the N-Terminal Nucleophile Hydrolase Superfamily, and the Use of Cells as a Catalyst for γ-Glutamylvalylglycine Production.

Although the purified Escherichia coli γ-glutamyltranspeptidase has much higher transpeptidation activity than hydrolysis activity, almost all γ-glutamyltranspeptidase activity is hydrolysis activity in vivo, that is when measured using the whole cells. By using the Met1 to Arg232 fragment of E. coli YiaT or the CapA of Bacillus subtilis subsp. Natto as an anchor protein, we succeeded in expressing E. coli γ-glutamyltranspeptidase on the extracellular surface of the cells, and these cells showed higher transpeptidation activity than hydrolysis activity in the presence of NaCl. Furthermore, E. coli cells overexpressing γ-glutamyltranspeptidase without an anchor from the T5 promoter maintained γ-glutamyltranspeptidase on the extracellular surface of the cells immediately after being harvested from the culture medium, but the enzyme was released from the extracellular surface of the cells subsequently in the absence of NaCl. Using these cells expressing γ-glutamyltranspeptidase on the extracellular surface, γ-Glu-Val-Gly, a kokumi compound, was successfully produced.

Feeding gastrostomy and duodenostomy using the round ligament of the liver versus conventional feeding jejunostomy after esophagectomy: a meta-analysis.

Esophageal cancer patients require enteral nutritional support after esophagectomy. Conventional feeding enterostomy to the jejunum (FJ) is occasionally associated with small bowel obstruction because the jejunum is fixed to the abdominal wall. Feeding through an enteral feeding tube inserted through the reconstructed gastric tube (FG) or the duodenum (FD) using the round ligament of the liver have been suggested as alternatives. This meta-analysis aimed to compare short-term outcomes between FG/FD and FJ. Studies published prior to May 2022 that compared FG or FD with FJ in cancer patients who underwent esophagectomy were identified via electronic literature search. Meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate Odds Ratios (ORs) with 95% confidence intervals (CIs). Five studies met inclusion criteria to yield a total of 1687 patients. Compared with the FJ group, the odds of small bowel obstruction (OR 0.09; 95% CI, 0.02-0.33), catheter site infection (OR 0.18; 95% CI, 0.06-0.51) and anastomotic leakage (OR 0.53; 95% CI, 0.32-0.89) were lower for the FG/FD group. Odds of pneumonia, recurrent laryngeal nerve palsy, chylothorax and hospital mortality did not significantly differ between the groups. The length of hospital stay was shorter for the FG/FD group (median difference, -10.83; 95% CI, -18.55 to -3.11). FG and FD using the round ligament of the liver were associated with lower odds of small bowel obstruction, catheter site infection and anastomotic leakage than FJ in esophageal cancer patients who underwent esophagectomy.

Reemployment and Recovery from Stigma after Metabolic/Bariatric Surgery: A Case Report and Review.

Bariatric surgery is performed worldwide to address morbid obesity. The benefits of this surgery are weight loss and a decrease in obesity-related complications. The relationship between metabolic/bariatric surgery and reemployment has been evaluated in Western countries, but few such studies have been performed in Japan because the number of metabolic/bariatric surgeries is small. Only a limited number of Japanese studies have evaluated the effects of bariatric surgery on obesity stigma, which affects employment and advancement opportunities for obese persons and may result in dismissal. We describe a case of bariatric surgery for a 39-year-old man who was dismissed from his job because of morbid obesity. Traditional weight loss methods failed to maintain weight loss and, preoperatively, the patient was receiving treatment for type 2 diabetes, hypertension, and abnormal lipid metabolism. He underwent sleeve gastrectomy and lost 50.4 kg (percent excess weight loss: 68.1%) in the first postoperative year. All medications were stopped after improvement in the results of laboratory blood tests and he was reemployed at 8 months after surgery. Increased social activity associated with employment is a factor in suppressing rebound weight gain after bariatric surgery, and weight loss associated with bariatric surgery helps decrease anti-obesity social stigma.

Agmatine production by Escherichia coli cells expressing SpeA on the extracellular surface.

A plasmid was constructed to express the CapA-SpeA fusion protein from the capA gene, which encodes one of the subunits of capsular poly-γ-glutamate synthetase of Bacillus subtilis subsp. natto, and the speA gene, encoding biosynthetic arginine decarboxylase (EC 4.1.1.19) of Escherichia coli, under the control of the T5 promoter. The expression of SpeA on the extracellular surface of cells was confirmed by confocal microscopy with the anti-SpeAE. coli antibody and anti-rabbit IgG L & H conjugated with Alexa Fluor 488. The constructed strain SH2290 produced 200 mM agmatine from 200 mM arginine, 20 mM MgSO4, 0.9 % NaCl, and 0.02 mg/mL pyridoxal 5'-phosphate (initial pH 5.3) by adjusting pH of the reaction mixture to 6.8 with HCl after each sampling during the reaction. The addition of pyridoxal 5'-phosphate to the reaction mixture was required for the maximum agmatine production. The present results demonstrate that the expression of enzymes on the extracellular surface of cells is a very powerful method for enzymatic conversion.

Biosynthesis of dillapiole/apiole in dill (Anethum graveolens): characterization of regioselective phenylpropene O-methyltransferase.

The phenylpropene volatiles dillapiole and apiole impart one of the characteristic aromas of dill (Anethum graveolens) weeds. However, very few studies have been conducted to investigate the chemical composition of volatile compounds from different developmental stages and plant parts of A. graveolens. In this study, we examined the distribution of volatile phenylpropenes, including dillapiole, in dill plants at various developmental stages. We observed that young dill seedlings accumulate high levels of dillapiole and apiole, whereas a negligible proportion was found in the flowering plants and dry seeds. Based on transcriptomics and co-expression approaches with phenylpropene biosynthesis genes, we identified dill cDNA encoding S-adenosyl-L-methionine-dependent O-methyltransferase 1 (AgOMT1), an enzyme that can convert 6- and 2-hydroxymyristicin to dillapiole and apiole, respectively, via the methylation of the ortho-hydroxy group. The AgOMT1 protein shows an apparent Km value of 3.5 µm for 6-hydroxymyristicin and is 75% identical to the anise (Pimpinella anisum) O-methyltransferase (PaAIMT1) that can convert isoeugenol to methylisoeugenol via methylation of the hydroxy group at the para-position of the benzene ring. AgOMT1 showed a preference for 6-hydroxymyristicin, whereas PaAIMT1 displayed a large preference for isoeugenol. In vitro mutagenesis experiments demonstrated that substituting only a few residues can substantially affect the substrate specificity of these enzymes. Other plants belonging to the Apiaceae family contained homologous O-methyltransferase (OMT) proteins highly similar to AgOMT1, converting 6-hydroxymyristicin to dillapiole. Our results indicate that apiaceous phenylpropene OMTs with ortho-methylating activity evolved independently of phenylpropene OMTs of other plants and the enzymatic function of AgOMT1 and PaAIMT1 diverged recently.