Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

The Synthesis of Biphasic Metabolites of Carfentanil.

Carfentanil is an ultra-potent synthetic opioid. The Russian police force used both carfentanil and remifentanil to resolve a hostage incident in Moscow. This reported use sparked an interest in the pharmacology and toxicology of carfentanil in the human body, and data on its metabolites were later published. However, there have been few studies on the synthesis of carfentanil metabolites, and biological extraction has also put forward large uncertainty in subsequent studies. The aim of the present study is to investigate the synthesis of biphasic metabolites that are unique to carfentanil. The purpose was to produce corresponding metabolites conveniently, quickly, and at low cost that can be used for comparison with published structures and to confirm the administration of carfentanil.

Clinical insights into hematologic malignancies and comparative analysis of molecular signatures of acute myeloid leukemia in different ethnicities using an artificial intelligence offering.

ABSTRACT: Next generation sequencing generates copious amounts of genomics data, causing manual interpretation to be laborious and non-scalable while remaining subjective (even for highly trained specialists). We evaluated the performance of the artificial intelligence-based offering Watson for Genomics (WfG), a variant interpretation platform, in hematologic malignancies for the first time.Next generation sequencing was performed for patients treated for various hematological malignancies at Hallym University Sacred Heart Hospital, South Korea, between December 2017 and August 2020 using a 54-gene panel. Both WfG and expert manual curation were used to evaluate the performance of WfG. Acute myeloid leukemia (AML) molecular profiles were compared between Koreans and other ethnic groups using a publicly available dataset.Seventy-seven patients were analyzed (AML: 45, myeloproliferative neoplasms: 12, multiple myeloma: 7, myelodysplastic syndromes: 6, and others: 7). The concordance between the manual and WfG interpretations of 35 variants in 11 random patients was 94%. Among all patients, WfG identified 39 (51%) with at least 1 clinically actionable therapeutic alteration (i.e., a variant targeted by a United States Food and Drug Administration [US FDA]-approved drug, off-label drug, or clinical trial). Moreover, 46% of these patients (18/39) had genes that were targeted by a US FDA-approved therapy. WfG identified diagnostic or prognostic insights in 65% of the patients with no targetable alterations. In those with AML, FLT3-internal tandem duplications or tyrosine kinase domain mutations were less frequent among Koreans than among Caucasians (6.7% vs 30.2%, P < .001) or Hispanics (6.7% vs 28.3%, P = .005), suggesting ethnic differences.Variant interpretation using WfG correlated well with manually curated expert opinions. WfG provided therapeutic insights (including variant-specific drugs and clinical trials that cannot easily be provided by expert manual curation), as well as diagnostic and/or prognostic information.

Four New Limonoids from the Barks of Toona ciliata.

Four new limonoids, toonayunnanaes F - I (1 - 4), and six known compounds (5 - 10) were isolated from the barks of Toona ciliata. Their structures were elucidated by thoroughly analyzing of NMR and HRMS data, and single-crystal X-ray diffraction of 1. The oxetane ring moiety in 1 was rare in limonoids and other natural products. Compound 1 showed nitric oxide (NO) inhibitory effect with an IC50 38.45 ± 0.41 µM in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages.

Predictive article recommendation using natural language processing and machine learning to support evidence updates in domain-specific knowledge graphs.

OBJECTIVES: Describe an augmented intelligence approach to facilitate the update of evidence for associations in knowledge graphs. METHODS: New publications are filtered through multiple machine learning study classifiers, and filtered publications are combined with articles already included as evidence in the knowledge graph. The corpus is then subjected to named entity recognition, semantic dictionary mapping, term vector space modeling, pairwise similarity, and focal entity match to identify highly related publications. Subject matter experts review recommended articles to assess inclusion in the knowledge graph; discrepancies are resolved by consensus. RESULTS: Study classifiers achieved F-scores from 0.88 to 0.94, and similarity thresholds for each study type were determined by experimentation. Our approach reduces human literature review load by 99%, and over the past 12 months, 41% of recommendations were accepted to update the knowledge graph. CONCLUSION: Integrated search and recommendation exploiting current evidence in a knowledge graph is useful for reducing human cognition load.

Acyclic diterpene and norsesquiterpene from the seed of Aphanamixis polystachya.

Aphanamoxene A-D (1-4), three new acyclic diterpene derivatives and one new acyclic norsesquiterpene were isolated from the seed of Aphanamixis polystachya. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR and HRESIMS. And the absolute configuration of 1 was achieved by Mosher method. These acyclic terpenoids (1-4) showed obvious nitric oxide production inhibitory activity on lipopolysaccharide-Induced RAW264.7 macrophages with IC50 values of 17.6 ± 1.4, 9.8 ± 0.7, 16.6 ± 1.2, and 14.2 ± 0.9 µM, respectively.

Immobilization of porcine pancreatic lipase onto a metal-organic framework, PPL@MOF: A new platform for efficient ligand discovery from natural herbs.

In terms of ligand fishing, the amount and the relative activity recovery of enzymes immobilized on magnetic particles and nanoparticles are not preeminent. Therefore, the metal-organic framework (MOF) UiO-66-NH2 was synthesized to immobilize the porcine pancreatic lipase (PPL) via precipitation-cross-linking, and the resulting novel biological matrices named PPL@MOF manifested high PPL loading capacity (98.31 mg/g) and relative activity recovery (104.4%). Moreover, the novel enzyme-MOF composite was applied to screen lipase inhibitors from Prunella vulgaris L. to enrich and improve the techniques of ligand fishing. As a result, 13 lipase ligands were obtained, and 12 compounds were determined by HPLC-Q-TOF-MS/MS. All of these ligands were further confirmed to be potential inhibitors through the verification of the activity assay and molecular docking. The proposed approach based on PPL@MOF was superior in terms of abundant protein loading capacity, high enzyme catalytic activity and easy preparation process. Taken together, our newly developed method provided a new platform for efficient discovering bioactive molecules from natural herbs.

Robot-Assisted versus Laparoscopic-Assisted Gastrectomy among Gastric Cancer Patients: A Retrospective Short-Term Analysis from a Single Institution in China.

BACKGROUND: The da Vinci robotic system was considered an effectively alternative treatment option for early gastric cancer patients in recent years. The aim of our study was to evaluate the safety and feasibility of robot-assisted gastrectomy in our center. METHODS: This study included 33 patients who underwent robot-assisted gastrectomy (RAG) and 88 patients who underwent laparoscopic-assisted gastrectomy (LAG) between January 2016 and April 2018. Clinicopathological characteristics, surgical parameters, postoperative recovery, and the learning curves of RAG were evaluated. RESULTS: Baseline characteristics between two groups were well balanced. The operation time of RAG was longer than that of LAG (333.1 ± 61.4 min vs. 290.6 ± 39.0 min, p = 0.001), and the estimated blood loss was 62.4 ± 41.2 ml in the RAG group and 77.7 ± 32.3 ml in the LAG group (p = 0.005), respectively. The mean number of examined lymph nodes in RAG was less than that in LAG (30.3 ± 10.2 vs. 37.4 ± 13.7, p = 0.008). However, RAG had an advantage in the dissection of No. 9 lymph nodes (3.4 ± 2.1 vs. 2.5 ± 1.6, p = 0.039). The incidence of postoperative complications was similar in both groups (p = 0.735). There were no significant differences in terms of postoperative recovery between the two groups. The learning curve of RAG showed that the CUSUM value decreased from the 8th case, which suggested a rapid learning curve among experienced surgeons on LAG operations. CONCLUSIONS: RAG was safe and feasible for gastric cancer patients, with superiority in the dissection of No. 9 lymph nodes.

Translating cancer genomics into precision medicine with artificial intelligence: applications, challenges and future perspectives.

In the field of cancer genomics, the broad availability of genetic information offered by next-generation sequencing technologies and rapid growth in biomedical publication has led to the advent of the big-data era. Integration of artificial intelligence (AI) approaches such as machine learning, deep learning, and natural language processing (NLP) to tackle the challenges of scalability and high dimensionality of data and to transform big data into clinically actionable knowledge is expanding and becoming the foundation of precision medicine. In this paper, we review the current status and future directions of AI application in cancer genomics within the context of workflows to integrate genomic analysis for precision cancer care. The existing solutions of AI and their limitations in cancer genetic testing and diagnostics such as variant calling and interpretation are critically analyzed. Publicly available tools or algorithms for key NLP technologies in the literature mining for evidence-based clinical recommendations are reviewed and compared. In addition, the present paper highlights the challenges to AI adoption in digital healthcare with regard to data requirements, algorithmic transparency, reproducibility, and real-world assessment, and discusses the importance of preparing patients and physicians for modern digitized healthcare. We believe that AI will remain the main driver to healthcare transformation toward precision medicine, yet the unprecedented challenges posed should be addressed to ensure safety and beneficial impact to healthcare.

Interactions of component (group) compatibility of Sanwu Huangqin Decoction in incubation model of rat liver microsomes / 中成药

AIM To study the interactions of component (group) compatibility of Sanwu Huangqin Decoction in incubation model of rat liver microsomes.METHODS With maackiain and ephedrine as internal standards,HPLC was adopted in the simultaneous content determination of total tlavonoids (baicalin,wogonoside,baicalein,wogonin and oroxylin A) from Scutellariae Radix and total alkaloids (oxymatrine,oxysophocarpine and matrine)from Sophorae flavescentis Radix in whole prescription component (group) compatibility and single medicinal material part (group) at seven time points (0,15,30,45,60,90 and 120 min),followed by the calculation of their in vitro metabolic rates.RESULTS In whole prescription component (group) compatibility,the contents of baicalin and wogonoside were first increased (0-0.5 h) and then decreased (0.5-2.0 h),those of baicalein,wogonin and oroxylin A showed increasing trends (more obvious within 0.5 h).The stable and gende metabolisms of various alkaloids reached balance within 20 min.CONCLUSION The bioavailability improvement and efficacy enhancement of total flavonoids from Scutellariae Radix may attribute to the compatibility with total alkaloids from Sophorae flavescentis Radix and total polysaccharides from Rehmanniae Radix in Sanwu Huangqin Decoction

Interactions of component (group) compatibility of Sanwu Huangqin Decoction in incubation model of rat liver microsomes / 中成药

AIM To study the interactions of component (group) compatibility of Sanwu Huangqin Decoction in incubation model of rat liver microsomes.METHODS With maackiain and ephedrine as internal standards,HPLC was adopted in the simultaneous content determination of total tlavonoids (baicalin,wogonoside,baicalein,wogonin and oroxylin A) from Scutellariae Radix and total alkaloids (oxymatrine,oxysophocarpine and matrine)from Sophorae flavescentis Radix in whole prescription component (group) compatibility and single medicinal material part (group) at seven time points (0,15,30,45,60,90 and 120 min),followed by the calculation of their in vitro metabolic rates.RESULTS In whole prescription component (group) compatibility,the contents of baicalin and wogonoside were first increased (0-0.5 h) and then decreased (0.5-2.0 h),those of baicalein,wogonin and oroxylin A showed increasing trends (more obvious within 0.5 h).The stable and gende metabolisms of various alkaloids reached balance within 20 min.CONCLUSION The bioavailability improvement and efficacy enhancement of total flavonoids from Scutellariae Radix may attribute to the compatibility with total alkaloids from Sophorae flavescentis Radix and total polysaccharides from Rehmanniae Radix in Sanwu Huangqin Decoction

Genetic Architecture of Domestication-Related Traits in Maize.

Strong directional selection occurred during the domestication of maize from its wild ancestor teosinte, reducing its genetic diversity, particularly at genes controlling domestication-related traits. Nevertheless, variability for some domestication-related traits is maintained in maize. The genetic basis of this could be sequence variation at the same key genes controlling maize-teosinte differentiation (due to lack of fixation or arising as new mutations after domestication), distinct loci with large effects, or polygenic background variation. Previous studies permit annotation of maize genome regions associated with the major differences between maize and teosinte or that exhibit population genetic signals of selection during either domestication or postdomestication improvement. Genome-wide association studies and genetic variance partitioning analyses were performed in two diverse maize inbred line panels to compare the phenotypic effects and variances of sequence polymorphisms in regions involved in domestication and improvement to the rest of the genome. Additive polygenic models explained most of the genotypic variation for domestication-related traits; no large-effect loci were detected for any trait. Most trait variance was associated with background genomic regions lacking previous evidence for involvement in domestication. Improvement sweep regions were associated with more trait variation than expected based on the proportion of the genome they represent. Selection during domestication eliminated large-effect genetic variants that would revert maize toward a teosinte type. Small-effect polygenic variants (enriched in the improvement sweep regions of the genome) are responsible for most of the standing variation for domestication-related traits in maize.

Study on suitable distribution areas of Cyathula officinalis in Sichuan province based on remote sensing and GIS / 中草药

Objective: To evaluate the suitability of Cyathula officinalis resources grown in Sichuan province, and provide a reference of the monitoring for traditional Chinese medicine resource. Methods: Taking the planting of C. officinalis in Sichuan province as an example, The topography, climate, soil, and vegetation of C. officinalis were researched using remote sensing and GIS techniques, binding environment factors in growing and adopting the analytic hierarchy process (AHP) and spatial analysis method. According to the different classification of index factors, the classification map of the suitable area for C. officinalis was obtained and the field measurements were combined to verify. Results: The C. officinalis resources in Sichuan province were mainly distributed in about 19 cities or autonomous prefectures such as Leshan City, Ya'an City, Yi Autonomous Prefecture of Liangshan, and Yibin City with suitability distribution areas of 3 633.52 km2 approximately and accounting for 0.76% of the total area. According to the field investigation, related documents, and information records, the suitability distribution based on RS and GIS correspond with the actual distribution areas of C. officinalis resources. Conclusion: It is a feasible method to divide the suitability distribution area of C. officinalis Kuan by using RS and GIS as quickly and accurately as possible. It can also provide a support on scientific and date basis to a complete investigation on suitable distribution areas, protection, rational development and utilization of C. officinalis and other medical materials.

Study on Suitable Distribution Areas of Kawa Kimichi Produced in Sichuan Province Based on Remote Sensing and GIS—A Case Study of Clematis Armandii / 世界科学技术-中医药现代化

The suitable distribution regions of medicinal clematis armandii in Sichuan province were extracted based on the suitable requirements of clematis armandii,comprehensive analysis and quantification on environmental indicators suitable forclematis armandii,following remote sensing (RS) and GIS spatial analysis,spatial database building and other technologies,extracted land use information.The results showed that regions suitable forclematis armandii were Gulin county,Xuyong county,Baoxing county and Tianquan county and other areas in Sichuan province.Among them,Gulin county and Xuyong county were the main distributed regions,which accounted for 23.2% and 25.4% of the total area,respectively.Through the comparison with the Chinese Materia Medica (CMM) Resource Database,this research result was basically coincided with census data from the Third National CMM.It also showed that RS and GIS technology were suitable for the investigation of suitable area of clematis armandii scientifically and feasibly.It improved the rational use of clematis armandii.It provided supporting information for rational planting of clematis armandii.It also of fered references for monitoring other wild herbs.

Study on suitable distribution areas of Notopterygium incisum in Sichuan province based on remote sensing and GIS / 中国中药杂志

Notopterygium incisum is the important medicinal materials of the Tibetan-Qiang medical system in China, also one of the rare and endangered medicinal materials in the Plateau areas in the meantime. Taking the planting of in Sichuan province as an example, research on the N. incisum in Sichuan utilize remote sensing and GIS techniques, bind growth environment factor, including height factor, average annual precipitation, average annual temperature, forest information, were chosen according to habitat conditions. And combine field measurement to verify. The results indicate that N. incisum resources in Sichuan province were mainly distributed in the alpine valley and the northwest of the plateau, which suitability distribution areas of 4145 km2 approximately and accounting for 2% of the total area. Suitability areas accounting for more than 2% of the respective total area in Heishui county, Lixian county, Xiaojin county, Kangding county, ect. According to the field investigation and the related document information record, drawn that the suitability distribution based on RS and GIS were corresponded with the actual distribution areas of N. incisum resources. It's feasible to divide the suitability distribution area of N. incisum using RS and GIS, which will provide a scientific basis for a comprehensive investigation of the distribution as well as its rational exploitation and protection.

[Research on laser spectrum detecting technology based on static Mach-Zehnder interferometer].

It is the key content of laser warning to reliably and real-time detect the type and characteristic parameters of incident laser. Coherent detection technology detects the information based on the coherence of laser, and is a kind of effective detection technology. In order to detect the incident laser's spectrum, a kind of device for laser detecting and real time spectrum measurement was designed, which measures the laser spectrum on the bases of coherent detecting technology, Fourier optics and optical signal processing. Using compact and static Mach-Zehnder interferometer as the coherent detection components, it can restrain the background light efficiently. The non-scanning mechanical parts allow fast spectrum detection, and narrow laser pulse can be detected. The real-time signal processing is realized by DSP and multi-channel frame subtraction technology to wipe off the background light, detect the laser and measure its spectrum. The result indicates that, using Mach-Zehnder interferometer and multi-channel frame subtraction technology can realize the laser pulse detection, and improve the measuring precision efficiently; 10 ns laser pulse can be detected and the wavelength measuring error is less than 10 nm.

[Research on the polymorphism of heart fatty acid-binding protein gene in Shanxi pig breeds and their crossbred populations using PCR-RFLP].

The genetic variation in 5' - upstream (Hinf I -RFLP)and the second intron (Hinf I *-RFLP, Hae III-RFLP)of heart fatty acid-binding protein(H-FABP)gene were detected with PCR-RFLP in 286 pigs including Mashen, Shanxi white pig and their crossbred populations. The results showed as follows: (1)Mashen presented only DD genotype while other populations varied,and Mashen crossbred populations had only 2 genotypes(DD, Dd) at the Hae III-RFLP site; (2)At the Hinf I -RFLP site of the 5' -upstream region, the crossbred population of Shanxi white pig and Duroc presented only HH genotype while other populations varied. Frequency of h allele in Mashen was 0.9727. (3)At the Hinf I *-RFLP site of the second intron, only Mashen presented 2 genotypes (BB, Bb), and frequency of B allele was 0.9667. (4)At the Hae III-RFLP and Hinf I *-RFLP sites, all populations were in Hardy-weinberg equilibrium.

[Variations of the zinc finger protein 161 gene in Chinese with or without high myopia].

To investigate the association between variations of ZFP161 gene and high myopia, A total of 204 probands with simple high myopia(< or = -6.0 dipoters) were collected while 116 normal persons from different families without high myopia or related disease were used as controls. Genomic DNA was prepared from the peripheral leucocytes. The coding sequences of ZFP161 gene in 320 subjects were analyzed by using exon-by-exon PCR-heteroduplex-SSCP analysis. Identification of the Variations by cloning and sequencing, combinated with controls and family analysis, was used to disclose the correlation between ZFP161 gene and high myopia. A mutation of ZFP161 gene was identified as an insertion of AT before the 58th nucleotide of intron 1 (IVS1 58-59)(1/204) and a variation of ZFP161 gene was identified as a heterozygous C to A of the 168th nucleotide in exon 2 (Codon56, GCC-->GCA, Ala56Ala). Ala56Ala is a non-sense mutation identified in 5 of the 204 patients and 3 of 116 controls. No evidence shows that these variations are responsible for high myopia.