Genetic and epigenetic control of the plant metabolome.

Plant metabolites are mainly produced through chemical reactions catalysed by enzymes encoded in the genome. Mutations in enzyme-encoding or transcription factor-encoding genes can alter the metabolome by changing the enzyme's catalytic activity or abundance, respectively. Insertion of transposable elements into non-coding regions has also been reported to affect transcription and ultimately metabolite content. In addition to genetic mutations, transgenerational epigenetic variations have also been found to affect metabolic content by controlling the transcription of metabolism-related genes. However, the majority of cases reported so far, in which epigenetic mechanisms are associated with metabolism, are non-transgenerational, and are triggered by developmental signals or environmental stress. Although, accumulating research has provided evidence of strong genetic control of the metabolome, epigenetic control has been largely untouched. Here, we provide a review of the genetic and epigenetic control of metabolism with a focus on epigenetics. We discuss both transgenerational and non-transgenerational epigenetic marks regulating metabolism as well as prospects of the field of metabolic control where intricate interactions between genetics and epigenetics are involved.

Prediction of Recurrence Pattern of Pancreatic Cancer Post-Pancreatic Surgery Using Histology-Based Supervised Machine Learning Algorithms: A Single-Center Retrospective Study.

BACKGROUND: Patients with pancreatic cancer (PC) have poor prognosis and a high incidence of recurrence. Since further treatment is applicable for specific recurrent events, it is important to predict recurrence patterns after surgery. This study aimed to identify and predict early and late recurrence patterns of PC using a histology-based machine learning model. PATIENTS AND METHODS: Patients who underwent upfront curative surgery for PC between 2001 and 2014 were included. The timing of recurrence and prognosis of each first recurrence site were examined. A histology-based supervised machine learning method, which combined convolutional neural networks and random forest, was used to predict the recurrence and respective sites of metastasis. Accuracy was evaluated using area under the receiver operating characteristic curve (AUC). RESULTS: In total, 524 patients were included. Recurrence in the liver accounted for 47.8% of all recurrence events in the first year after surgery. Meanwhile, recurrence in the lung occurred later and could become apparent more than 5 years post-surgery, with indications for further surgery. In terms of substantial distant organ metastases, liver and lung metastases were identified as representative early and late recurrence events. The predictive AUCs of the machine learning model for training and test data were 1.000 and 0.861, respectively, and for predicting nonrecurrence were 1.000 for both. CONCLUSIONS: We identified the liver and lung as early and late recurrence sites, which could be distinguished with high probability using a machine learning model. Prediction of recurrence sites using this model may be useful for further treatment of patients with PC.

Clinical impact of intraoperative bile leakage during laparoscopic liver resection.

BACKGROUND: Despite the increasing number of laparoscopic liver resection (LLR) procedures, postoperative bile leakage (POBL) remains a major complication. We occasionally experienced intraoperative bile leakage (IOBL) during LLR and managed it within the restrictions of laparoscopic surgery. However, there have been no reports about IOBL in LLR. We therefore investigated the impact of IOBL on postoperative outcomes and its predictive factors. METHODS: We reviewed 137 patients who underwent LLR from April 2016 to March 2019 at our institute and assigned them to IOBL-positive or IOBL-negative groups. We compared clinicopathological characteristics and perioperative outcomes. Patients were further divided into four groups according to IOBL pattern, and the frequency of POBL in each was calculated. Predictors of IOBL were identified using multivariate logistic regression analysis. RESULTS: There were 30 and 107 patients in the IOBL-positive and IOBL-negative groups, respectively. In the IOBL-positive group, operative time and postoperative hospital stays were significantly longer (P < 0.001). The frequency of POBL was significantly higher in the IOBL-positive group (P = 0.006). The IOBL-positive group was divided into two subgroups: IOBL from the transected parenchyma (IOBL-TP, n = 18) and from the main Glissonean pedicle (IOBL-mGP, n = 12). The IOBL-negative group was divided into two subgroups: bile staining in the mGP (BS-mGP, n = 9) and no change (NC, n = 98). POBL occurred in 11% (n = 2/18) of patients with IOBL-TP, 25% (n = 3/12) of those with IOBL-mGP, 11% (n = 1/9) of those with BS-mGP, and 1% (n = 1/98) of those with NC. Age, diabetes mellitus, indocyanine green retention rate, and Glissonean approach were predictors of IOBL (P < 0.05). CONCLUSIONS: IOBL was relatively common during LLR and resulted in a higher incidence of POBL. Depending on the predictive factors, IOBL must be promptly identified and appropriately managed.

A neat wheat trick to hide genes from selection.

A recent study by Li et al. demonstrated that the removal of like heterochromatin protein 1 (LHP1) in common wheat causes developmental drawbacks, yet confers resistance to stripe rust infection. Due to its role in regulating diversified defense genes, LHP1 was suggested to be an epigenetic gatekeeper potentially promoting adaptive evolution in allopolyploid wheat.

Combined thoracoscopic and laparoscopic surgery for epiphrenic diverticulum with associated gastroesophageal reflux disease: a case report.

BACKGROUND: Surgery is indicated for symptomatic epiphrenic esophageal diverticula. Based on the features of a case, thoracoscopic or laparoscopic approaches may be used. Epiphrenic diverticula are often associated with esophageal motility disorders, but cases of reflux esophagitis have rarely been reported. In this report, we describe a case of an epiphrenic esophageal diverticulum with reflux esophagitis, which was successfully treated by thoracoscopic diverticulectomy and laparoscopic fundoplication. CASE PRESENTATION: A 69-year-old man visited the hospital with a chief complaint of eructation and hiccup. Upper gastrointestinal endoscopy revealed a diverticulum in the left wall of the esophagus, which was 37-45 cm distal to the incisors. High-resolution manometry (HRM) showed no esophageal motility disorders. Due to the large size of the diverticulum, a thoracoscopic resection of the esophageal diverticulum was performed. Additionally, the patient had reflux esophagitis due to a hiatal hernia. The anti-reflux mechanism would be more impaired during the diverticulectomy; therefore, we decided that anti-reflux surgery should be performed simultaneously. Thoracoscopic esophageal diverticulectomy and laparoscopic Dor fundoplication were performed. The patient had an uncomplicated postoperative course and was discharged on the tenth operative day. He has been symptom-free without acid secretion inhibitors for 21 months after the surgery. CONCLUSIONS: We described a rare case of a large epiphrenic diverticulum with reflux esophagitis. A good surgical outcome was achieved by thoracoscopic resection of the diverticulum and laparoscopic Dor fundoplication.

Reactive lymphoid hyperplasia of the liver after surgery for advanced sigmoid colon cancer: a case report.

We report a case of reactive lymphoid hyperplasia (RLH) mimicking colorectal liver metastases (CRLM) on preoperative workup that was clinically indistinguishable. A 78-year-old woman was found to have locally-advanced sigmoid cancer (T4), and then treated with radical sigmoidectomy. One year after the surgery, plain computed tomography (CT) revealed a low-density area in the right hepatic lobe. Metastatic liver tumors could not be ruled out with CT/ magnetic resonant imaging (MRI) and positron emission tomography-CT . Based on these findings, the patient was diagnosed with CRLM at S7 of the liver. The patient underwent right posterior sectionectomy. The tumor was adjacent to the right hepatic vein; however, no invasion was observed. The patient was pathologically diagnosed as having RLH. The patient showed no signs of recurrence 16 months after initial surgery. RLH is clinically indistinguishable from CRLM. Further evaluation is required to elucidate the effective strategies of detecting and treating hepatic RLH.

Essential updates 2020/2021: Recent topics in surgery and perioperative therapy for esophageal cancer.

In this review, we focused on four topics, namely, minimally invasive esophagectomy (MIE), robot-assisted minimally invasive esophagectomy (RAMIE), conversion and salvage surgery, and neoadjuvant and adjuvant therapy, based on notable reports published in the years 2020 and 2021. It seems that while the short-term outcomes of minimally invasive Ivor Lewis esophagectomy (MIE-IL) were better than those of open Ivor Lewis esophagectomy (OE-IL), there were no significant differences in the long-term outcomes between MIE-IL and OE-IL. Similarly, the short-term outcomes of minimally invasive McKeown esophagectomy (MIE-MK) were better than those of open McKeown esophagectomy (OE-MK), while there were no significant differences in the long-term outcomes between MIE-MK and OE-MK. Furthermore, the short-term outcomes of robot-assisted minimally invasive Ivor Lewis esophagectomy (RAMIE-IL) were superior to those of completely minimally invasive Ivor Lewis esophagectomy (CMIE-IL). On the other hand, there were advantages and disadvantages in relation to the short-term outcomes of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK) as compared with completely minimally invasive McKeown esophagectomy (CMIE-MK). However, there were no significant differences in the long-term outcomes between RAMIE-MK and CMIE-MK. Further research is needed to evaluate of short-term and long-term outcomes of transmediastinal esophagectomy with and without robotic assistance. Both induction chemotherapy and induction chemoradiotherapy appear to be promising to secure a higher rate of conversion surgery. Neoadjuvant chemoimmunotherapy and chemoimmunoradiotherapy have shown promising results and are expected as new powerful therapies.

Prognostic impact of preoperative skeletal muscle change from diagnosis to surgery in patients with perihilar cholangiocarcinoma.

Background: Loss of skeletal muscle mass is a prognostic factor after surgery for gastrointestinal cancers. The treatment for perihilar cholangiocarcinoma (PHC) is a highly invasive surgery. Biliary drainage and portal vein embolization, which can prolong the preoperative waiting time (PWT), are often required before surgery. Assuming that the skeletal muscle mass can change during PWT, we investigated the clinical effect of skeletal muscle change on surgical outcomes of PHC. Methods: We retrospectively reviewed the medical records of 89 patients who underwent curative surgery for PHC from January 2013 to December 2019. We defined the psoas muscle area (PMA) at the third lumbar vertebra as the skeletal muscle mass. The PMA just before surgery was divided by that at the time of diagnosis, and we defined it as the rate of change of PMA (CPMA). Patients were divided into two groups according to CPMA: wasting (n = 44, below the median CPMA) and no-change (n = 45, above the median CPMA). Results: The median PWT was 63 d, and CPMA was 96.1%. The median recurrence-free survival and overall survival were significantly shorter in the wasting group than in the no-change group (8.0 vs 33.2 mo, P = 0.001 and 14.2 vs 48.7 mo, P < 0.001, respectively). Multivariate analysis revealed that histological differentiation, R1 resection, lymph node metastasis, and preoperative skeletal muscle wasting were independent prognostic factors of PHC. Conclusion: This study suggests that preoperative skeletal muscle wasting in patients with PHC has a negative effect on survival outcomes.

Laparoscopic Heller myotomy and Dor fundoplication following an unsuccessful peroral endoscopic myotomy.

BACKGROUND: Achalasia is an esophageal motility disorder that presents as dysphagia and severely affects quality of life. An esophageal myotomy has been the golden standard for treatment. Peroral endoscopic myotomy (POEM) as a first-line therapy has an acceptable outcome. However, after the clinical failure of POEM, appropriate second-line therapy is rather controversial. Here, we present the first published case in English of a patient who was successfully treated using laparoscopic Heller myotomy (LHM) with Dor fundoplication following an unsuccessful POEM. CASE PRESENTATION: A 64-year-old man with type 1 achalasia who had been previously treated with POEM visited our hospital for further treatment. After undergoing LHM with Dor fundoplication, his Eckardt score improved from 3 to 0 points. On a timed barium esophagogram (TBE), the barium height improved from 119 mm/119 mm (1 min/5 min) to 50 mm/45 mm. No significant complications have occurred postoperatively for 1 year. CONCLUSION: Treating refractory achalasia is challenging, and treatment options are controversial. LHM with Dor fundoplication after POEM could be a safe and efficient option for the treatment of refractory achalasia.

Long-term survival after surgical resection for bone metastasis from pancreatic cancer: A case report.

INTRODUCTION: Pancreatic cancer (PC) is highly malignant and metastatic; however, bone metastases are rare. Although the effectiveness of conversion surgery for distant metastases of PC has been reported in a few cases, there are no reports on surgical resection for bone metastases. Here, we report a case of long-term survival after resection of bone metastasis from PC. PATIENT CONCERNS: A 60-year-old woman underwent pancreaticoduodenectomy after neoadjuvant chemoradiotherapy for pancreatic head cancer. At 28 months after surgery, multiple lung metastases from PC were diagnosed, and chemotherapy was administered. After 59 months, chemotherapy was terminated because all target lesions had disappeared on imaging. DIAGNOSIS: At 77 months after the initial surgery, bone metastasis in the left 9th rib was detected by positron emission tomography/computed tomography, which was performed due to elevated carbohydrate antigen 19-9 levels. INTERVENTIONS: Chemotherapy was readministered as the initial treatment. Subsequently, due to the long-term well-controlled status of the recurrence site and the absence of other metastases, thoracoscopic-assisted partial resection of the left 9th rib was performed 128 months following pancreaticoduodenectomy. Pathological examination revealed adenocarcinoma metastasis from PC. OUTCOMES: The patient is currently alive without recurrence 44 months after resection for bone metastasis and 172 months after the initial surgery. CONCLUSION: Surgical resection may be favorable in patients with bone metastasis of PC that is well-controlled with chemotherapy.

Ultrastrong underwater adhesion on diverse substrates using non-canonical phenolic groups.

Robust underwater adhesion is challenging because a hydration layer impedes the interaction between substrates and adhesives. Phenolic adhesives inspired by marine creatures such as mussels were extensively studied, but these adhesives have not reached the adhesion strength and substrate diversity of Man-made dry adhesives. Here, we report a class of ultrastrong underwater adhesives with molecular phenolic designs extending beyond what nature has produced. These non-canonical phenolic polymers show versatile adhesion on various materials, with adhesion strengths exceeding 10 MPa on metal. Incorporating even just a small amount (<10%) of non-canonical phenolic groups into a polymer is sufficient for dramatically enhancing underwater adhesion, suggesting that this new class of phenolic materials will be incorporated into various industrial polymer systems in the future.

A Fabry-Pérot cavity coupled surface plasmon photodiode for electrical biomolecular sensing.

Surface plasmon resonance is a well-established technology for real-time highly sensitive label-free detection and measurement of binding kinetics between biological samples. A common drawback, however, of surface plasmon resonance detection is the necessity for far field angular resolved measurement of specular reflection, which increases the size as well as requiring precise calibration of the optical apparatus. Here we present an alternative optoelectronic approach in which the plasmonic sensor is integrated within a photovoltaic cell. Incident light generates an electronic signal that is sensitive to the refractive index of a solution via interaction with the plasmon. The photogenerated current is enhanced due to the coupling of the plasmon mode with Fabry-Pérot modes in the absorbing layer of the photovoltaic cell. The near field electrical detection of surface plasmon resonance we demonstrate will enable a next generation of cheap, compact and high throughput biosensors.

Feasibility of endoscopic hand suturing on rectal anastomoses in ex vivo porcine models.

Prevention of postoperative anastomotic leakage in rectal surgery is still required. This study investigated the feasibility of endoscopic hand suturing (EHS) on rectal anastomosis ex vivo. By using isolated porcine colon, we prepared ten anastomoses 6-10 cm from the virtual anus. Then, we sutured anastomoses intraluminally by EHS, which involved a continuous suturing method in 5 cases and a nodule suturing method with extra corporeal ligation in 5 cases. Completeness of suturing, number of stitches, procedure time and presence of stenosis were investigated. Furthermore, the degree of stenosis was compared between the two suturing methods. In all cases, EHS were successfully completed. The median number of stitches and procedure time was 8 and 5.8 min, respectively. Stenosis was created in all continuous suturing cases whereas none was seen in nodule suturing cases. The shortening rate was significantly greater in the continuous suturing method than in the nodule suturing method. Intraluminal reinforcement of rectal anastomosis by EHS using nodule suturing with extra corporeal ligation is feasible without stenosis, which may be helpful as a countermeasure against possible postoperative anastomotic leakage in rectal surgery.

Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis.

Plant genomes remain highly fragmented and are often characterized by hundreds to thousands of assembly gaps. Here, we report chromosome-level reference and phased genome assembly of Ophiorrhiza pumila, a camptothecin-producing medicinal plant, through an ordered multi-scaffolding and experimental validation approach. With 21 assembly gaps and a contig N50 of 18.49 Mb, Ophiorrhiza genome is one of the most complete plant genomes assembled to date. We also report 273 nitrogen-containing metabolites, including diverse monoterpene indole alkaloids (MIAs). A comparative genomics approach identifies strictosidine biogenesis as the origin of MIA evolution. The emergence of strictosidine biosynthesis-catalyzing enzymes precede downstream enzymes' evolution post γ whole-genome triplication, which occurred approximately 110 Mya in O. pumila, and before the whole-genome duplication in Camptotheca acuminata identified here. Combining comparative genome analysis, multi-omics analysis, and metabolic gene-cluster analysis, we propose a working model for MIA evolution, and a pangenome for MIA biosynthesis, which will help in establishing a sustainable supply of camptothecin.

Aqueous olanexidine versus aqueous povidone-iodine for surgical skin antisepsis on the incidence of surgical site infections after clean-contaminated surgery: a multicentre, prospective, blinded-endpoint, randomised controlled trial.

BACKGROUND: Surgical site infection (SSI) is the most common problem after surgery. Although several guidelines have indicated the efficacy of antiseptics, such as chlorhexidine-alcohol and povidone-iodine, in reducing SSI rate, the optimal recommendation is still not established. Olanexidine might have higher bactericidal activity than other antiseptic agents. However, no randomised study has evaluated the efficacy and safety of olanexidine over conventional antiseptics. We compared the effect of aqueous olanexidine and aqueous povidone-iodine on the incidence of SSI following clean-contaminated surgery. METHODS: This was a multicentre, prospective, randomised, blinded-endpoint superiority trial for surgical skin antisepsis in clean-contaminated gastrointestinal and hepatobiliary pancreatic surgeries in four Japanese hospitals. Patients aged 20 years or older who underwent elective clean-contaminated wound surgery were randomly assigned in a 1:1 replacement ratio using a computer-generated block randomisation. Patients were randomly assigned to surgical skin antisepsis with an aqueous formulation of 1·5% olanexidine or surgical skin antisepsis with an aqueous formulation of 10% povidone-iodine before surgery. We used olanexidine in a ready-to-use applicator, and povidone-iodine was administered by a brush or by compression using pliers. Both antiseptics were applied from the papilla with a cranial limit and to the upper thigh with a caudal limit. The antiseptics were allowed to dry for 3 min, and then surgery started. Participants, some investigators, and data analysts were masked to treatment allocation. Participant enrolment was done by non-masked investigators. The primary outcome was 30-day SSI assessed in the intention-to-treat population. The surgical wound site of each participant was observed daily. After discharge, participants underwent at least one outpatient visit within 30 days after surgery. This trial is registered with University hospital Medical Information Network, 000031560. FINDINGS: Between June 10, 2018, and April 18, 2019, 883 patients were assessed for eligibility. 587 patients were eligible and 294 received olanexidine and 293 received aqueous povidone-iodine before surgery. 30-day SSI occurred in 19 (7%) patients in the olanexidine group and 39 patients (13%) patients in the povidone-iodine group (adjusted risk difference -0·069; 90% CI -0·109 to -0·029; adjusted risk ratio [RR] 0·48, 90% CI 0·30 to 0·74; p=0·002). Five patients (2%) in the olanexidine group and five (2%) in the povidone-iodine group developed adverse skin reactions (adjusted RR 0·99, 95% CI 0·29 to 3·40; p=1·00). INTERPRETATION: Olanexidine significantly reduced the occurrence of overall SSI and superficial incisional SSI compared with aqueous povidone-iodine in clean-contaminated surgery. Our results indicate that olanexidine might have a role to prevent SSI in patients who undergo clean-contaminated surgeries. FUNDING: Keio University and Ohyama Health Foundation.

Interplay of hot electrons from localized and propagating plasmons.

Plasmon-induced hot-electron generation has recently received considerable interest and has been studied to develop novel applications in optoelectronics, photovoltaics and green chemistry. Such hot electrons are typically generated from either localized plasmons in metal nanoparticles or propagating plasmons in patterned metal nanostructures. Here we simultaneously generate these heterogeneous plasmon-induced hot electrons and exploit their cooperative interplay in a single metal-semiconductor device to demonstrate, as an example, wavelength-controlled polarity-switchable photoconductivity. Specifically, the dual-plasmon device produces a net photocurrent whose polarity is determined by the balance in population and directionality between the hot electrons from localized and propagating plasmons. The current responsivity and polarity-switching wavelength of the device can be varied over the entire visible spectrum by tailoring the hot-electron interplay in various ways. This phenomenon may provide flexibility to manipulate the electrical output from light-matter interaction and offer opportunities for biosensors, long-distance communications, and photoconversion applications.Plasmon-induced hot electrons have potential applications spanning photodetection and photocatalysis. Here, Hoang et al. study the interplay between hot electrons generated by localized and propagating plasmons, and demonstrate wavelength-controlled polarity-switchable photoconductivity.

Orientation of multi-hair follicles in nonbald men: perpendicular versus parallel.

BACKGROUND: There has been much debate about the orientation of multi-hair grafts in order to obtain an appearance of fullness after the hair transplantation. OBJECTIVES: To analyze natural orientation of multi-hair follicles and the influence of hair flow from the crown swirl. METHODS: Natural orientation of follicles was analyzed microscopically in 100 nonbald men: a clockwise whorl flow group (50 men) and a counterclockwise group (50 men). RESULTS: The majority of multi-hair follicles were oriented perpendicular to the radial line from the whorl in both the groups. The percentage of perpendicular orientation was large in the peripheral and middle scalp areas (49-79%), and it decreased in the vertex (38-49%, p<.05 or .01). The percentages of parallel, right oblique, and left oblique orientation were small in the peripheral area with a slight increase in the vertex (3-12% vs. 14-24%, p<.05 or .01). CONCLUSION: Original orientation of multi-hair follicles was mainly perpendicular to the radial line from the whorl irrelevant to the crown swirl hair flow. Multi-hair grafts transplanted perpendicularly would look similar to the natural hair follicles in the front half of the scalp.