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Elucidating the biosynthetic pathways of natural products has been a major focus of biochemistry and pharmacy. However, predicting the whole pathways from target molecules to metabolic building blocks remains a challenge. Here we propose READRetro as a practical bio-retrosynthesis tool for planning the biosynthetic pathways of natural products. READRetro effectively resolves the tradeoff between generalizability and memorability in bio-retrosynthesis by implementing two separate modules; each module is responsible for either generalizability or memorability. Specifically, READRetro utilizes a rule-based retriever for memorability and an ensemble of two dual-representation-based deep learning models for generalizability. Through extensive experiments, READRetro was demonstrated to outperform existing models by a large margin in terms of both generalizability and memorability. READRetro was also capable of predicting the known pathways of complex plant secondary metabolites such as monoterpene indole alkaloids, demonstrating its applicability in the real-world bio-retrosynthesis planning of natural products. A website (https://readretro.net) and open-source code have been provided for READRetro, a practical tool with state-of-the-art performance for natural product biosynthesis research.

The anterior chamber angle (ACA) is a critical factor in posterior chamber phakic intraocular lens (EVO Implantable Collamer Lens [ICL]) implantation. Herein, we predicted postoperative ACAs to select the optimal ICL size to reduce narrow ACA-related complications.Regression models were constructed using pre-operative anterior segment optical coherence tomography metrics to predict postoperative ACAs, including trabecular-iris angles (TIAs) and scleral-spur angles (SSAs) at 500 µm and 750 µm from the scleral spur (TIA500, TIA750, SSA500, and SSA750). Data from three expert surgeons were assigned to the development (N = 430 eyes) and internal validation (N = 108 eyes) datasets. Additionally, data from a novice surgeon (N = 42 eyes) were used for external validation.Postoperative ACAs were highly predictable using the machine-learning (ML) technique (extreme gradient boosting regression [XGBoost]), with mean absolute errors (MAEs) of 4.42 degrees, 3.77 degrees, 5.25 degrees, and 4.30 degrees for TIA500, TIA750, SSA500, and SSA750, respectively, in internal validation. External validation also showed MAEs of 3.93 degrees, 3.86 degrees, 5.02 degrees, and 4.74 degrees for TIA500, TIA750, SSA500, and SSA750, respectively. Linear regression using the pre-operative anterior chamber depth, anterior chamber width, crystalline lens rise, TIA, and ICL size also exhibited good performance, with no significant difference compared with XGBoost in the validation sets.We developed linear regression and ML models to predict postoperative ACAs for ICL surgery anterior segment metrics. These will prevent surgeons from overlooking the risks associated with the narrowing of the ACA.Using the proposed algorithms, surgeons can consider the postoperative ACAs to increase surgical accuracy and safety.

Background Optimal sizing for phakic intraocular lens (EVO ICL with KS-AquaPort) implantation plays an important role in preventing postoperative complications. We aimed to formulate optimal lens sizing using ocular biometric parameters measured by the Heidelberg anterior segment optical coherence tomography (AS-OCT) device. Methods We retrospectively analyzed 892 eyes of 471 healthy subjects treated with intraocular collamer lens (ICL) and assigned them to development (80%) and validation (20%) sets. We built vault prediction models using the development set via classic linear regression methods, partial least squares, and least absolute shrinkage and selection operator (LASSO) regression techniques. We evaluated prediction abilities based on the Bayesian information criterion (BIC) to select the best prediction model. The performance was measured using Pearson’s correlation coefficients and the mean squared error (MAE) between the achieved and predicted vaults. Results Measurements of aqueous depth (AQD), anterior chamber volume, anterior chamber angle (ACA) distance, spur-to-spur distance, crystalline lens thickness (LT), and white-to-white distance from ANTERION were highly associated with the ICL vault. The LASSO model using the AQD, ACA distance, and LT showed the best BIC results for postoperative ICL vault prediction. In the validation dataset, the LASSO model showed the strongest correlation (r = 0.582, P

Introduction Moxibustion therapy has been used in oriental medicine for symptoms of irritable bowel syndrome such as diarrhoea and constipation. This study aimed to evaluate the efficacy and safety of different doses of moxibustion for irritable bowel syndrome (IBS). Methods This study was conducted at Semyung Korean Medical Hospital, Chungbuk, Republic of Korea. Twenty-four patients (12 males, 12 females) aged 18–30 years who were diagnosed with IBS using the Rome III criteria were included. trial In this triple blind randomised controlled trial patients were allocated to receive either 3-cone moxibustion or 1-cone moxibustion. Moxa was applied to Guan Yuan (CV4) for 20 min. The Bowel Symptom Severity Scale (BSSS) score was used as the primary outcome measure; the Irritable Bowel Syndrome Severity Scale – Korean Version (IBSSS-K) score, heart rate variability (HRV), visceral sensitivity questionnaire, and a pattern identification questionnaire were secondary outcome measures. Results There was a significant difference in IBSSS-K scores after moxibustion in both the 3CMG (score: before: 217.50 ± 79.95, after: 137.42 ± 68.70, p = 0.021) and 1CMG groups (score: before: 217.67 ± 98.77, after: 112.25 ± 71.11, p = 0.006). There were no significant differences in the BSSS scores, IBSSS-K scores, Qi stagnation questionnaire scores, or cold-heat pattern questionnaire scores, between the two groups. Conclusions Different doses of moxibustion resulted in similar efficacy levels for the treatment of IBS. These preliminary findings suggest that moxibustion therapy may be effective and can be safe in improving the symptoms of IBS.

Seven hundred ninety-eight oil wells were set fire, damaged, and gushed oil and resulted on a crude oil contaminated area over 300 km2 include dry oil lakes at the end of Iraqi war. The United Nation Compensation Commission (UNCC) recommended remediation of crude oil contaminated soil as physical chemical and thermal processes due to the oil sludge and high concentration of TPH. In this study, indigenous oil-emulsifying bacteria in Kuwait crude oil contaminated soil was cultured via enrichment culture method. Bacterial composition of enrichment culture investigated by phylogenetic analysis of 16S rRNA gene sequences obtained through high-throughput sequencing. The majority of enriched bacteria belonged to the order of Flavobacteriales (56.38%), Burkholderiales (16.13%), and Pseudomonadales (12.22%). Using those indigenous microorganisms, biological process consists of bio-washing, biocatalytic, and biopile was operated for 20 days in lab-scale. Initial TPH concentrations measured by hexane extraction method (HEM) and GC-FID method were 46,096 mg/kg and 34,153 mg/kg, respectively. Removal rates of TPH after 20days operation were 68% (HEM) and 86% (GC-FID). Therefore, Kuwait crude oil contaminated soil can be remediated by combine biological process such as bio-washing and biopile process.

Introduction This study is designed to evaluate the efficacy and safety of treating irritable bowel syndrome patients with a proper dose of moxibustion. Methods and analysis This study will be a 4-week-long, randomised controlled pilot clinical trial. Twenty-four patients will be recruited and randomly allocated to 1 of 2 groups: a 3 moxibustion treatment intervention group and a 1 moxibustion treatment control group. Both groups will receive two moxibustion sessions a week for 4 weeks (8 sessions in total). The primary outcome will be measured using the Bowel Symptom Severity Scale. The inclusion criteria are as follows. The patients will be between 18 and 30 years old and of either gender. The patients will have experienced repeated abdominal pain or discomfort (i.e., an uncomfortable sensation not described as pain) at least 3 times per month in association with two or more of the following over the previous 3 months: (a) improvement with defecation; (b) onset associated with a change in the frequency of defecation; (c) onset associated with a change in the form (appearance) of stool. All included patients will have provided written consent to the clinical ethics committee and have agreed with both the clinical trial plan and follow-up observations. Ethics and dissemination This research protocol has been reviewed and approved by the institutional review board of the trial centre (Semyung Korean Medicine Hospital, IRB No. 2016-06-01). The results will be published in a journal and will be disseminated both electronically and in print.

The application of biological processes for remediation of the aged crude oil-contaminated soil of Kuwait can be an inefficient way, thus, this study developed 20 d-sequential biowashing and biopile processes where the biowashing step uses an enrichment culture of the indigenous soil bacterial community and the biopile step includes hemoglobin-catalyzed oxidation (HCO). The residual total petroleum hydrocarbons (TPH) concentrations and CO2 generation were measured to determine the removal efficiency, and the bacterial community changes were studied to investigate the effect of the sequential processes on the soil indigenous bacterial community. The enrichment culture grown on hemoglobin showed an increased surface activity, and this promoted desorption and emulsification of crude oil from the soil sample in the biowashing step resulting in 75% TPH removal. Potential surfactant-producing bacterial species were observed in the soil sample after biowashing. The HCO in the beginning of the biopile step removed 21% of the residual TPH, and further TPH removal was observed with a longer biopile period. Overall, the sequential biowashing and biopile processes removed 86% TPH. The results show that the developed sequential biowashing and biopile processes can be used to efficiently remediate the aged crude oil-contaminated soil of Kuwait.

Fourteen compounds were isolated from the flowers of Inula japonica THUNB. (Asteraceae), including two new compounds, (1S,2S,4S,5S,8S,10R)-2-acetoxy-4,3-dihydroxy-pseudoguai-7(11)-en-12,8-olide (1) and (1S,2S,4S,5S,8S,10R)-2,4,13-trihydroxy-pseudoguai-7(11)-en-12,8-olide (2), and twelve known compounds, budlein B (3), 6β-hydroxytomentosin (4), 6-deacetoxybritanin (5), 4-epipulchellin (6), britanin (7), tomentosin (8), (+)-dihydroquercetin (9), (-)-syringaresinol (10), quercetagetin 3,4'-dimethyl ether (11), luteolin (12), britanin G (13) and inuchinenolide C (14). Structures of 1 and 2 were determined based on one and two dimensional (1D)- and (2D)-NMR data and Mosher's esterification method. Compounds 9 and 12 showed inhibitory activities toward DNA topoisomerase I with IC50 values of 55.7 and 37.0 µM, respectively, compared to camptothecin (CPT) with an IC50 of 24.5 µM. Compounds 7-9 and 11-14 exhibited more potent inhibitory activity against topoisomerases II with IC50 values of 6.9, 3.8, 3.0, 6.9, 10.0, 14.7 and 13.8 µM, respectively, than that of etoposide (VP-16) with an IC50 of 26.9 µM. Compounds 4-7 and 10-14 exhibited weak cytotoxicities to the selected cancer cell lines.

A HPLC-DAD method was developed for simultaneous determination of four marker compounds, kaempferol-3-O-rutinoside, safflomin A, safflomin B and bidenoside C, in the extract of the flowers of Carthamus tinctorius Linne. Natural samples were extracted in 50% aqueous methanol by ultra-sonication for 60 min. Marker compounds were separated on a C18 column by two-step gradient elution of mobile phase (acetonitrile/water) at a flow rate of 0.75 mL/min and detected at 210 nm. The retention times of safflomin A and safflomin B were shifted according to the pH of the mobile phase. The optimized analytical method was validated to confirm linearity, precision, accuracy and stability of marker compounds. The method was successfully employed to analyze 17 natural samples from different regions, and the data matrix was monitored and visualized by principal component analysis. The assay method could be applied for quality control of the flowers of C. tinctorius Linne.