READRetro: natural product biosynthesis predicting with retrieval-augmented dual-view retrosynthesis.

Plants, as a sessile organism, produce various secondary metabolites to interact with the environment. These chemicals have fascinated the plant science community because of their ecological significance and notable biological activity. However, predicting the complete biosynthetic pathways from target molecules to metabolic building blocks remains a challenge. Here, we propose retrieval-augmented dual-view retrosynthesis (READRetro) as a practical bio-retrosynthesis tool to predict the biosynthetic pathways of plant natural products. Conventional bio-retrosynthesis models have been limited in their ability to predict biosynthetic pathways for natural products. READRetro was optimized for the prediction of complex metabolic pathways by incorporating cutting-edge deep learning architectures, an ensemble approach, and two retrievers. Evaluation of single- and multi-step retrosynthesis showed that each component of READRetro significantly improved its ability to predict biosynthetic pathways. READRetro was also able to propose the known pathways of secondary metabolites such as monoterpene indole alkaloids and the unknown pathway of menisdaurilide, demonstrating its applicability to real-world bio-retrosynthesis of plant natural products. For researchers interested in the biosynthesis and production of secondary metabolites, a user-friendly website (https://readretro.net) and the open-source code of READRetro have been made available.

Girdling behavior of the longhorn beetle modulates the host plant to enhance larval performance.

BACKGROUND: Preingestive behavioral modulations of herbivorous insects on the host plant are abundant over insect taxa. Those behaviors are suspected to have functions such as deactivation of host plant defenses, nutrient accumulation, or modulating plant-mediated herbivore interactions. To understand the functional consequence of behavioral modulation of insect herbivore, we studied the girdling behavior of Phytoecia rufiventris Gautier (Lamiinae; Cerambycidae) on its host plant Erigeron annuus L. (Asteraceae) that is performed before endophytic oviposition in the stem. RESULTS: The girdling behavior significantly increased the larval performance in both field monitoring and lab experiment. The upper part of the girdled stem exhibited lack of jasmonic acid induction upon larval attack, lowered protease inhibitor activity, and accumulated sugars and amino acids in compared to non-girdled stem. The girdling behavior had no effect on the larval performance of a non-girdling longhorn beetle Agapanthia amurensis, which also feeds on the stem of E. annuus during larval phase. However, the girdling behavior decreased the preference of A. amurensis females for oviposition, which enabled P. rufiventris larvae to avoid competition with A. amurensis larvae. CONCLUSIONS: In conclusion, the girdling behavior modulates plant physiology and morphology to provide a modulated food source for larva and hide it from the competitor. Our study implies that the insect behavior modulations can have multiple functions, providing insights into adaptation of insect behavior in context of plant-herbivore interaction.

Three consecutive cytosolic glycolysis enzymes modulate autophagic flux.

Autophagy serves as an important recycling route for the growth and survival of eukaryotic organisms in nutrient-deficient conditions. Since starvation induces massive changes in the metabolic flux that are coordinated by key metabolic enzymes, specific processing steps of autophagy may be linked with metabolic flux-monitoring enzymes. We attempted to identify carbon metabolic genes that modulate autophagy using VIGS screening of 45 glycolysis- and Calvin-Benson cycle-related genes in Arabidopsis (Arabidopsis thaliana). Here, we report that three consecutive triose-phosphate-processing enzymes involved in cytosolic glycolysis, triose-phosphate-isomerase (TPI), glyceraldehyde-3-phosphate dehydrogenase (GAPC), and phosphoglycerate kinase (PGK), designated TGP, negatively regulate autophagy. Depletion of TGP enzymes causes spontaneous autophagy induction and increases AUTOPHAGY-RELATED 1 (ATG1) kinase activity. TGP enzymes interact with ATG101, a regulatory component of the ATG1 kinase complex. Spontaneous autophagy induction and abnormal growth under insufficient sugar in TGP mutants are suppressed by crossing with the atg101 mutant. Considering that triose-phosphates are photosynthates transported to the cytosol from active chloroplasts, the TGP enzymes would be strategically positioned to monitor the flow of photosynthetic sugars and modulate autophagy accordingly. Collectively, these results suggest that TGP enzymes negatively control autophagy acting upstream of the ATG1 complex, which is critical for seedling development.

Is Age-Predicted Maximal Heart Rate Applicable in Patients With Heart or Lung Disease?

OBJECTIVE: To compare the predicted and actual maximal heart rate (HRmax) values in the cardiopulmonary exercise test (CPET). METHODS: We retrospectively investigated 1,060 patients who underwent a CPET between January 2016 and April 2020 at our institution's cardiopulmonary rehabilitation center. The following patients were included: those aged >20 years, those tested with a treadmill, and those who underwent symptom-limited maximum exercise testing- reaching ≥85% of the predicted HRmax (62% if taking beta-blockers) and highest respiratory exchange ratio ≥1.1. Ultimately, 827 patients were included in this study. Data on diagnosis, history of taking beta-blockers, age, body mass index (BMI), and CPET parameters were collected. Subgroup analysis was performed according to age, betablockers, BMI (low <18.5 kg/m2, normal, and high ≥25 kg/m2), and risk classification. RESULTS: There was a significant difference between the actual HRmax and the predicted value (p<0.001). Betablocker administration resulted in a significant difference in the actual HRmax (p<0.001). There were significant differences in the moderate-to-high-risk and low-risk groups and the normal BMI and high BMI groups (p<0.001). There was no significant difference between the elderly and younger groups. We suggest new formulae for HRmax of cardiopulmonary patients: estimated HRmax=183-0.76×age (the beta-blocker group) and etimated HRmax=210-0.91×age (the non-beta-blocker group). CONCLUSION: Age-predicted HRmax was significantly different from the actual HRmax of patients with cardiopulmonary disease, especially in the beta-blocker group. For participants with high BMI and moderate-tosevere risk, the actual HRmax was significantly lower than the predicted HRmax.

Detection of pharyngeal perforation during fiberoptic endoscopic evaluation of swallowing in a person with cervical spinal cord injury in the intensive care unit: a case report.

Endotracheal tube insertion and mechanical ventilation are indicated in spinal cord injury patients; however, dysphagia can occur after extubation. The resultant complications of dysphagia may increase the length of hospital stay and mortality. Therefore, dysphagia should be evaluated after extubation. This case report introduces a rare case of finding pharyngeal perforation during the fiberoptic endoscopic evaluation of swallowing (FEES) in patients with cervical spine injuries in the intensive care unit. A 71-year-old male patient met with a road traffic accident. The patient underwent C3-4 posterior fusion and C3-4 anterior cervical discectomy and fusion. After successful extubation, the patient underwent FEES to assess swallowing function. During FEES, the metallic plate was found to be exposed through mucosal erosion, and swelling was observed at the surgical site at the hypopharynx. The nasogastric tube was removed to prevent secondary damage and infection at the operation site and the patient was received conservative therapy. The FEES endoscope machine is portable so it can be easily applied at the bedside to intensive care unit patients. In addition, FEES allows the identification of anatomical abnormalities of the oropharynx and abnormalities of vocal cord. Thus, it is recommended to do FEES to check anatomical abnormalities as well as dysphagia in patients in the intensive care unit.

Identification of acquired tracheoesophageal fistula after tracheostomy decannulation by videofluoroscopic swallowing study: A case report.

RATIONALE: Videofluoroscopic swallowing study (VFSS) is a noninvasive radiographic procedure that examines the oral, pharyngeal, and cervical esophageal stages of swallowing. Tracheoesophageal fistula (TEF) is difficult to diagnose depending on its size and location. However, how VFSS can be of benefit in the diagnosis of TEF has not been reported yet. PATIENT CONCERNS: A 64-year-old man who had been tracheostomized post spinal tumor resection surgery at the cervical level 1 to 2, had his tracheostomy tube removed approximately 25 years ago. After decannulation, he reported coughing while swallowing food, foreign sensation in the neck and repeated bouts of pneumonia ever since. DIAGNOSIS: VFSS revealed, for the first time, acquired TEF after tracheostomy decannulation as the cause of repetitive aspiration pneumonia. INTERVENTION: VFSS was performed in this case. OUTCOMES: In the background of suspected TEF based on VFSS results, the patient underwent a computed tomography scan of the chest and airway in the prone position, followed by bronchoscopy, which confirmed the existence of a TEF. He then underwent primary closure of the fistula. The patient had an uneventful recovery and is currently symptom-free 10 months after the surgery. LESSONS: This case alerts clinicians to the possibility of TEF as a diagnosis when the aspirate leaks from the upper esophagus and through the posterior wall of trachea in the esophageal phase of VFSS.

A novel assessment of abdominal pseudohernia after thoracolumbar vertebral compression fractures using surface electromyography and ultrasonography: A case report.

RATIONALE: An abdominal pseudohernia is a protrusion of the abdominal wall that there is no actual muscular disruption. This report presents a case in which abdominal muscle activities were accurately and quantitatively measured using ultrasonography (US) and surface electromyography in a patient with abdominal pseudohernia. PATIENT CONCERNS: A 62-year-old man presented with a marked protrusion on the left abdomen with increasing abdominal pressure. DIAGNOSES: First, the thickness of the abdominal muscle was measured with US while the patient constantly blew the positive expiratory pressure device. When the force was applied to the abdomen, the mean thickness of the muscle layer on the lesion site was found to be thinner. Second, the activities of the abdominal muscles were measured using surface electromyography by attaching electrodes to 8 channels at the same time. When the same pressure was applied on both sides of the abdomen, more recruitment occurred to compensate for muscle weakness at the lesion site. Through the previous 2 tests, the decrease in muscle activity in the lesion area could be quantitatively evaluated. Third, the denervation of the muscle was confirmed using US-guided needle electromyography. INTERVENTIONS: The patient in this case was wearing an abdominal binder. In addition, he had been training his abdominal muscles through McGill exercise and breathing exercises such as with a positive expiratory pressure device. OUTCOMES: The patient was able to understand his symptoms. A follow-up test will be performed to see if there is any improvement. LESSONS: By using these outstanding assessment methods, proper diagnosis and rehabilitation treatment strategies can be developed.

Control of Crystallinity in PbPc:C60 Blend Film and Application for Inverted Near-Infrared Organic Photodetector.

Inverted near-infrared (NIR) organic photodetectors (OPDs) are required to combine the OPDs with an n-channel silicon-based integrated circuit. NIR absorption in the 930-960 nm range is important because the intensity of solar irradiation is low in this wavelength regime. Here, we controlled the crystallinity of lead(II) phthalocyanine (PbPc) in a PbPc:C60 blend film to obtain NIR absorption. To form a triclinic phase responsible for NIR light absorption, a substrate was heated during fabrication and C60 was used as a templating layer, as well as an electron extraction layer, for an inverted structure. NIR absorption near 950 nm was enhanced, and the structural properties of the film changed dramatically. The OPD with enhanced NIR absorption exhibited a responsivity of 244 mA/W and an external quantum efficiency of 31.1% at a reverse bias of -3 V and 970 nm. The OPD detectivity also increased to 9.01 × 1012 and 1.36 × 1011 cm Hz1/2/W under a zero bias and a reverse bias of -3 V, respectively.

Justicia procumbens Extract (DW2008) Selectively Suppresses Th2 Cytokines in Splenocytes and Ameliorates Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma.

DW2008 is an anhydrous ethanol extract of Justicia procumbens produced by Dong-Wha Pharmaceutical, Inc., Co. as a candidate anti-asthmatic drug. In this study, DW2008 selectively reduced T helper 2 (Th2) cytokines in mouse splenocytes and ameliorated ovalbumin-induced airway inflammation by downregulating pulmonary infiltration of differential inflammatory cells and Th2 cytokines more than a decoction or ethanol extract of J. procumbens did in a mouse asthma model. DW2008 also significantly inhibited airway hyperresponsiveness and reduced the thickness of the airway epithelium. HPLC analysis showed that the major peaks (justicidin A and B) of DW2008 were higher than those of the other extracts. Justicidin A and B significantly suppressed Th2 cytokine levels in mouse spleen cells and exhibited a protective effect in ovalbumin-induced airway inflammation. Our findings indicate that DW2008 effectively inhibits allergic airway inflammatory reactions and airway hyperresponsiveness in a mouse model of asthma, suggesting its potential as an anti-asthmatic agent.

Enhancement of the Fill Factor through an Increase of the Crystallinity in Fullerene-Based Small-Molecule Organic Photovoltaic Cells.

We report that the crystallinity of C70 is improved significantly if CuI is used as a templating layer, leading to remarkable enhancement of hole mobilities from 8.32 × 10(-6) to 3.26 × 10(-5) cm(2)/(V s). As a result, the use of the templating layer in C70-based solar cells with low donor concentration resulted in significant improvement of the fill factor from 0.51 to 0.57 and the power conversion efficiency from 5.56% to 6.23% under simulated AM 1.5G, 1 sun irradiation. This result demonstrates that the CuI templating layer is effective at improving the crystallinity of the fullerene derivatives as well as the donor materials.

Multilayer epitaxial growth of lead phthalocyanine and C(70) using CuBr as a templating layer for enhancing the efficiency of organic photovoltaic cells.

The molecular orientation and crystallinity of donor and acceptor molecules are important for high-efficiency organic photovoltaic cells (OPVs) because they significantly influence both the absorption of light and charge-transport characteristics. We report that the templating effect extends to multilayers to increase the crystallinity and to modify the orientation of the crystals of lead phthalocyanine (PbPc) and C70 layers at the same time by adopting CuBr as a new templating layer on indium tin oxide (ITO). The formation of a monoclinic phase with a preferred orientation of (320) for PbPc and a fcc phase with a preferred orientation of (220) for C70 on the PbPc layer is revealed by X-ray diffraction (XRD) patterns. The multilayer epitaxy results in an increase of the exciton diffusion lengths from 5.6 to 8.8 nm for PbPc and from 6.9 to 13.8 nm for C70 to enhance the power conversion efficiency (PCE) of the planar heterojunction OPVs composed of PbPc and C70 from 1.4 to 2.3%. The quasi-epitaxy model is proposed to explain the multilayer epitaxy.

Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes.

Temperature-sensitive liposomes (TS-liposomes) have been studied for chemotherapeutic purposes to enhance the release of anticancer drugs at tumor sites. In this study, we prepared poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAM) and polyethylene glycol (PEG)-modified TS-liposomes (PETS-liposomes). PETS-liposomes significantly increased in vitro drug release in serum compared with PEG-fixed or PNIPAM-AAM-modified liposomes. Furthermore, incorporation of both PNIPAM-AAM and PEG into PETS-liposomes enhanced the stabilities of liposomes in serum by inhibiting protein adsorption. In addition, to investigate the therapeutic efficacy of doxorubicin (DOX)-loaded PETS-liposomes, the in vivo antitumor activity of liposomes in combination with hyperthermia was evaluated in a B16F10 melanoma tumor-bearing mouse model. PETS-liposomes showed much higher levels of tumor growth inhibition than PEG-fixed or PNIPAM-AAM-modified TS-liposomes. Moreover, the antitumor activity of PETS-liposomes was enhanced significantly when they were administered in combination with hyperthermia. PETS-liposomes were found to be highly efficacious carriers for the in vivo delivery of anticancer drugs, and to have potential anticancer applications in combination with hyperthermia.

Identification of a novel non-carbohydrate molecule that binds to the ribosomal A-site RNA.

We report the identification of a novel compound that binds to the Escherichia coli 16S ribosomal A-site. Binding by the compound was observed using nuclear magnetic resonance and mass spectrometry techniques. We show that the compound binds in the same position in the A-site RNA as occupied by the aminoglycoside class of antibiotics.