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Abstract In biosynthesis multiple kinds of reactive intermediates are generated, transported, and reacted across different parts of organisms, enabling highly sophisticated synthetic reactions. Herein we report a convergent synthetic approach, which utilizes dual intermediates of cationic and carbanionic species in a single step, hinted at by the ideal reaction conditions. By reactions of unsaturated precursors, such as enamines, with a superacid in a flow microreactor, cationic species, such as iminium ions, are generated rapidly and irreversibly, and before decomposition, they are transported to react with rapidly and independently generated carbanions, enabling direct C-C bond formation. Taking advantage of the reactivity of these double reactive intermediates, the reaction take place within a few seconds, enabling synthetic reactions which are not applicable in conventional reactions.

Objectives: Chronic constipation is a common gastrointestinal disorder, and management is crucial. Computed tomography (CT) is useful for evaluating rectal fecal mass but limited owing to radiation exposure, cost, and inaccessibility at certain facilities. Ultrasonography (US) avoids these pitfalls, but it is unknown whether it accurately assesses rectal feces. In this study, we evaluated the diagnostic performance of US compared with CT as the gold standard for assessing rectal feces. Methods: We prospectively evaluated rectal fecal mass retention using US performed within 1 h of CT to assess the degree of agreement between methodologies. Rectal stool findings were evaluated on three levels: no stool (R1), presence of stool (R2), and hard stool filling (R3). Results: The sample included 100 patients (55 men, 45 women), of whom 47 were constipated. The kappa coefficients for rectal content detection were excellent between US and CT (p

Abstract Background and Aim Ischemic colitis (IC) is a benign disease associated with acute lower gastrointestinal bleeding and frequent recurrence. While several studies have investigated risk factors for IC onset, few have assessed the risk factors for recurrent IC. This study aimed to identify risk factors for recurrent IC. Methods Potential risk factors for recurrence were assessed by examining medical records and laboratory findings in this single‐center retrospective study. We extracted the following data from the patients' medical records: patient characteristics, clinical signs and symptoms, laboratory findings, method of treatment, length of hospital stay, disease course, and the frequency of IC morbidities. Patients with IC were selected from a total of 439 312 patients over an 11‐year period. Patients were divided into recurrent and nonrecurrent IC groups. Results In total, 225 patients met the diagnostic criteria for IC during the specified study period; of these, 204 patients (90.7%) and 21 patients (9.3%) were included in the nonrecurrent and recurrent IC groups, respectively. Univariate and multivariate analyses showed a significant association between IC recurrence and both cerebral infarction (P = 0.008, odds ratio [OR] = 6.3) and history of appendectomy (P = 0.0005, OR = 6.2). The median (interquartile range [IQR]) follow‐up time for all patients was 1556 (353–2768) days; this was much longer than the median (IQR) time to recurrence of 291 (64–907) days in the recurrent IC group. Conclusion The results of this study suggest that prior cerebral infarction and appendicectomy may be risk factors for IC recurrence.

ABSTRACTIn Kenya and many other African countries, improving rice productivity is vital for future food security. To improve rice productivity in Kenya, near-isogenic lines (NIL) were developed by introducing Gn1a and WFP, genes that function to increase grain number per panicle by increasing secondary and primary rachis-branches, into NERICA 1, a registered variety in Kenya. The aim of this study was to determine whether the introduction of these genes has the potential to improve rice productivity under tropical highland conditions in central Kenya. Field experiments were conducted in 2016 and 2017 at a lowland rice field in Mwea, Kenya, under different nitrogen fertilization conditions using three lines of NERICA 1 introgressed with Gn1a and/or WFP (NIL-Gn1a, NIL-WFP, and NIL-Gn1a+WFP) and their recurrent parents, NERICA 1. Two years of field experiments revealed that the introgression lines enhanced grain yield by increasing the number of primary and secondary rachis-branches and the number of grains per panicle. Gn1a and WFP showed additive effects and the introgression of both genes alleviated the negative effects on yield components observed in the introgressed lines, resulting in higher grain yield. Sufficient nitrogen fertilization was required to increase yield in the single-gene introgression lines. However, the line with both Gn1a and WFP achieved reasonable yields even under low fertilizer conditions in Mwea, Kenya. As these introgression lines have similar growing characteristics to their parent variety, they are expected to contribute to increased rice production in Kenya and similar environments in sub-Saharan Africa.

Abstract We developed an electrocatalytic reduction of (hetero)aryl halides under mild conditions using a proton exchange membrane (PEM) reactor. This approach allows substituting the halogeno groups on the aryl rings to protons by water and electron. Taking advantage of this transformation, deuterodehalogenation of (hetero)aryl halides, which forms mono‐deuterated (hetero)aryls, was demonstrated using heavy water as a deuterium source. The current efficiency and deuterium ratio could be increased by the conditions optimized by machine‐learning method, Bayesian optimization.

Abstract As climate change intensifies, the development of resilient rice that can tolerate abiotic stresses is urgently needed. In nature, many wild plants have evolved a variety of mechanisms to protect themselves from environmental stresses. Wild relatives of rice may have abundant and virtually untapped genetic diversity and are an essential source of germplasm for the improvement of abiotic stress tolerance in cultivated rice. Unfortunately, the barriers of traditional breeding approaches, such as backcrossing and transgenesis, make it challenging and complex to transfer the underlying resilience traits between plants. However, de novo domestication via genome editing is a quick approach to produce rice with high yields from orphans or wild relatives. African wild rice, Oryza longistaminata, which is part of the AA-genome Oryza species has two types of propagation strategies viz. vegetative propagation via rhizome and seed propagation. It also shows tolerance to multiple types of abiotic stress, and therefore O. longistaminata is considered a key candidate of wild rice for heat, drought, and salinity tolerance, and it is also resistant to lodging. Importantly, O. longistaminata is perennial and propagates also via rhizomes both of which are traits that are highly valuable for the sustainable production of rice. Therefore, O. longistaminata may be a good candidate for de novo domestication through genome editing to obtain rice that is more climate resilient than modern elite cultivars of O. sativa.

Paw San Hmwe (PSH) is an indigenous rice variety from Myanmar with a good taste, a pleasant fragrance, and excellent elongation ability during cooking. However, its low yield potential and strong photoperiod sensitivity reduce its productivity, and it is vulnerable to climate changes during growth. To improve the photoperiod insensitivity, yield, and plant stature of PSH, the high-yield genes Grain number 1a (Gn1a) and Wealthy Farmer’s Panicle (WFP), together with the photoperiod insensitivity trait, were introgressed into PSH via marker-assisted backcross breeding and phenotype selection. For the photoperiod insensitivity trait, phenotypic selection was performed under long-day conditions during the dry season. After foreground selection of Gn1a and WFP via simple sequence repeat genotyping, genotyping-by-sequencing was conducted to validate the introgression of target genes and determine the recurrent parent genome recovery of the selected lines. The improved lines were insensitive to photoperiod, and the Gn1a and WFP introgression lines showed significantly higher numbers of primary panicle branches and spikelets per panicle than the recurrent parent, with comparative similarity in cooking and eating qualities. This study successfully improved PSH by decreasing its photoperiod sensitivity and introducing high-yield genes via marker-assisted selection. The developed lines can be used for crop rotation and double-season cropping of better-quality rice.

Walruses seem to use various acoustic signals in social context. So, the auditory faculty is seems to be important for walruses. Can walruses understand another animals' vocal information using auditory sense? This study tested whether a male walrus could discriminate human vocal words and perform different actions corresponding to each one under various conditions. The subject, a male walrus (Odobenus rosmarus) named Pou, was set on the ground, and the experimenter spoke one of the ten words to the subject under the following conditions; (1) The experimenter stood close to the subject and spoke each vocal stimulus wearing a black cloak and goggles so that the experimenter's eye and body movements would not influence the subject's behavior, (2) A wooden board was placed between the experimenter and the subject so that the subject could not see the experimenter, (3) A wooden board was placed between the experimenter and the subject so that the subject could not to see the experimenter, and the experimenter uttered each vocal stimulus through an audio speaker. Under each condition, when the subject performed the correct action corresponding to the vocal stimulus, he was rewarded with a piece of fish. As a result, the subject responded correctly to almost all the human vocal stimuli in every condition, including when the speaker was not visible. This means that he was indeed responding to the vocal words and not the experimenter's cues. This study demonstrated that walruses can hear and identify human vocal words using their auditory sense and can form correspondence between vocal words and their meanings.

Abstract Numerous studies have revealed distinct differences in the profiles of gut microbiota between non-obese and obese individuals. To date, however, little is known if any disparities in the community of gut microbiota exist between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) subjects. We therefore aimed to comprehensively characterize the gut microbiota and circulating metabolites in serum from both MHO and MUO residing in the remote island, Kumejima, where the prevalence of obesity is one of the highest in Japan, and explored possible correlations between the gut microbiota profile and markers of metabolic syndrome. Results revealed that MUO showed significantly higher levels of genera such as g_Succinivibrio, g_Granulicatella, g_Brachyspira, g_Oribacterium and g_Atopobium in comparison to MHO. Moreover, abundance of g_Succinivibrio, g_Brachyspira and g_Atopobium were positively correlated with value of fasting insulin, HOMA-R, circulating triglycerides, diastolic blood pressure, BMI, body weight, waist circumference and HbA1c. In addition, MUO compared to MHO showed an imbalance of serum metabolites, with a significant elevation in 2-oxoisovaleric acid, pyruvic acid, 2-hydroxybutyric acid, and creatine. Our data highlight unmet needs in precision approaches for the treatment of obesity, targeting the gut microbiota profile and serum metabolites in a distinct population affected by obesity.

This retrospective cohort study compared the number of newly diagnosed patients, stage at diagnosis, and detection process of gastrointestinal cancers based on hospital-based cancer registry data at two tertiary Japanese hospitals. The pre-COVID-19 period was from January 2017 to February 2020, with phase 1 (midst of COVID-19 pandemic) from March to December 2020 and phase 2 (the transition period to the “new normal”) from January to December 2021. Each month, the number of patients diagnosed with esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers were aggregated, classified by stage and detection process, and compared, including a total of 6453 patients. The number of colorectal Stage 0-II patients decreased significantly in phase 1 and increased in phase 2. The total number of colorectal cancer patients returned to pre-COVID-19 levels (mean monthly patients [SD]: 41.61 [6.81] vs. 36.00 [6.72] vs. 46.00 [11.32]). The number of patients with gastric cancer Stage I significantly decreased in phase 2 following phase 1. The number of gastric cancer patients decreased significantly from pre-COVID-19 levels (30.63 [6.62] vs. 22.40 [5.85] vs. 24.50 [4.15]). During phase 2, the number of patients diagnosed after screening with colorectal cancer increased significantly, whereas that with gastric cancer remained considerably lower. The number of Stage III colorectal and gastric cancer patients increased significantly from the pre-COVID-19 levels. Thus, gastric cancer may not be optimally screened during phases 1 and 2. There was a significant increase in patients with Stage III colorectal and gastric cancers from the pre-COVID-19 period; hence, the stage at diagnosis may have progressed.

Abstract Fusobacterium nucleatum is associated with the progression of colorectal cancer. Thus, the possibility of preventing colorectal cancer or its progression by targeting F. nucleatum has been explored. As F. nucleatum is associated with periodontitis, we analysed whether treating periodontitis could influence F. nucleatum abundance in the colon. Patients with colorectal tumours who underwent colonoscopy were recruited. Patients diagnosed with periodontitis by a dentist were treated for approximately 3 months. Endoscopic resection of colorectal tumours was performed after periodontitis treatment, and resected tumours were pathologically classified as high-(HGD) or low-grade dysplasia (LGD). Saliva and stool samples were collected before and after the treatment. Of the 58 patients with colorectal tumours, 31 were included in the study, 16 showed improvement in periodontitis, and 11 showed no improvement. Stool F. nucleatum levels before treatment were significantly lower in the LGD group than in the HGD group. A significant decrease in faecal F. nucleatum levels was observed in patients who underwent successful treatment but not in those whose treatment failed. Salivary F. nucleatum levels were not altered in patients despite periodontal treatment. Thus, successful periodontitis treatment reduces stool F. nucleatum levels and may aid research on periodontitis and suppression of colorectal cancer development.

Background: Chronic constipation leads to poor quality of life, and treatment remains unsatisfactory for patients. In Japan, magnesium oxide has been commonly used as the first choice of treatment for constipation; however, there are some cases of low satisfaction with magnesium oxide treatment. Linaclotide has recently been used to treat chronic constipation. In this study, we will examine whether linaclotide improves symptoms and quality of life in patients showing insufficient response to magnesium oxide. Methods: This is an exploratory multicenter open-label study. The target number of patients is 64: 32 patients with and 32 without abdominal symptoms. Patients with chronic idiopathic constipation or irritate bowel syndrome with constipation diagnosed according to the Rome-IV criteria are eligible. Patients prescribed 0.99–2 g/day of magnesium oxide for at least 4 weeks will be included. Those who consent to the study will continue taking magnesium oxide for 2–4 weeks, and defecation will be documented. Patients who meet the criteria will be prescribed linaclotide (0.5 mg) daily for 12 weeks. The primary endpoint is a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score after 12 weeks of treatment. Conclusion: This is the first study to investigate the usefulness of linaclotide as a second-line treatment for chronic constipation. We will test the efficacy of treatment of constipation in patients with inadequate response to magnesium oxide. Trial registration: This study is registered with the Japan Registry of Clinical Trials (jRCT, jRCTs031200048).

We achieved an integration of a lithiation of aryl bromides, a zincation of thus-generated aryllithiums, and a Negishi coupling of the arylzinc with an aryl halide in one flow. Taking advantages of flow microreactors, biaryls bearing a wide range of functional groups, especially biaryls bearing multiple electrophilic-functionalities were synthesized.

Intestinal microbiota may play a significant role in the development and progression of mild cognitive impairment (MCI). In addition, sex differences in the prevalence of MCI and intestinal microbiota are likely to exist. Therefore, this study investigated the association between MCI and intestinal microbiota by comparing Japanese patients in their 70s with MCI (11 males and 18 females) and disease-free controls (17 males and 23 females), taking sex into account. In both sexes, Clostridium_XVIII, Eggerthella, Erysipelatoclostridium, Flavonifractor, and Ruminococcus 2 were the more abundant taxa in the MCI group, whereas Megasphaera, Oscillibacter, Prevotella, Roseburia, and Victivallis were less abundant. Based on these characteristics, it was hypothesized that the composition of the intestinal microbiota in the MCI group leads to dysregulation of the intestinal microbiota, increased intestinal and blood–brain barrier permeability, and increased chronic neuroinflammation, with the long-term persistence of these abnormalities ultimately leading to cognitive decline. Furthermore, risk estimation models for MCI based on intestinal microbiota data were developed using structural equation modeling. These tests discriminated between the MCI and control groups. Incorporating these factors into intestinal microbiota testing using stool samples may be an efficient method to screen individuals with MCI.

Abstract Background When performing colorectal endoscopic submucosal dissection (ESD) in obese patients, technically difficult cases are sometimes experienced because of difficulty with the insertion of the colonoscope, poor scope maneuverability, or an abundance of fat tissue in the submucosal layer. Since the association between obesity and colorectal ESD has not been investigated, we evaluated the clinical impact of obesity in patients who underwent colorectal ESD. Methods We retrospectively reviewed 535 patients who underwent colorectal ESD between April 2012 and February 2019. Patients were divided into three groups based on their body mass index (BMI): a control group (BMI

Abstract Objective Collagen and elastin are the main components of the female pelvic tissue. We investigated whether single nucleotide polymorphisms (SNPs) of collagen type 1 alpha 1 (COL1A1), collagen type 3 alpha 1 (COL3A1), and lysyl oxidase-like (LOXL) 1 and 4 were associated with the onset of pelvic organ prolapse (POP) in Japanese women. Fifty-two women with POP and 28 women without POP were included. SNPs were identified using the TaqMan® SNP genotyping assay. Results Age, parity, and lower urinary tract symptoms were significantly higher in the POP group than in the control group. The prevalence of genotypes with rs2862296 polymorphism of LOXL4, an enzyme essential for extracellular matrix remodeling, was different between the POP (26.9% for GG, 51.9% for AG) and control groups (14.8% for GG, 33.3% for AG). However, polymorphisms of COL1A1, COL3A1, and LOXL1 were not related to the onset of POP. In the multivariate logistic regression analysis, age was significantly associated with the occurrence of POP. In the univariate analysis, LOXL4 polymorphism was associated with the onset of POP in Japanese women. The knowledge of acquired risk factors and polymorphisms in the genomic background of patients with POP may help prevent POP via early conservative interventions.

There are diverse phenotypes of castration‐resistant prostate cancer, including neuroendocrine disease, that vary in their sensitivity to drug treatment. The efficacy of BET and CBP/p300 inhibitors in prostate cancer is attributed, at least in part, to their ability to decrease androgen receptor (AR) signalling. However, the activity of BET and CBP/p300 inhibitors in prostate cancers that lack the AR is unclear. In this study, we showed that BRD4, CBP, and p300 were co‐expressed in AR‐positive and AR‐null prostate cancer. A combined inhibitor of these three proteins, NEO2734, reduced the growth of both AR‐positive and AR‐null organoids, as measured by changes in viability, size, and composition. NEO2734 treatment caused consistent transcriptional downregulation of cell cycle pathways. In neuroendocrine models, NEO2734 treatment reduced ASCL1 levels and other neuroendocrine markers, and reduced tumour growth in vivo. Collectively, these results show that epigenome‐targeted inhibitors cause decreased growth and phenotype‐dependent disruption of lineage regulators in neuroendocrine prostate cancer, warranting further development of compounds with this activity in the clinic. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]