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The C(sp3)-H functionalization of O-pentafluorobenzoyl ketone oximes was implemented under visible light irradiation with copper complexes as catalysts. The reactions involve iminyl-radical-mediated intramolecular hydrogen atom transfer as the key step, with the iminyl radicals being generated via copper-effected N-O cleavage. The reaction afforded 3,4-dihydro-2H-pyrroles under the conditions of [Cu(DPEphos)(bcp)]PF6 and DABCO, while γ-pentafluorobenzoyloxy ketones were produced predominantly when [Cu(dpp)2]PF6 and InCl3·4H2O were used as catalysts.

IntroductionThe management of women with clinical early-stage cervical cancer and lymph node involvement detected intraoperatively is heterogeneous and controversial. This paper presents the protocol of a systematic review and meta-analysis regarding the management of this specific population of patients. This proposed study aims to answer the question: does completion of radical hysterectomy improve the oncological outcomes of women with clinical early-stage cervical cancer and intraoperatively detected nodal involvement?Methods and analysisThis protocol is drafted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines, and the proposed study will be conducted in accordance with the standard guidelines of ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ and ‘Meta-analysis of Observational Studies in Epidemiology reporting guideline’. Comprehensive literature searches will be performed in PubMed, Embase, Scopus, and Web of Science. The screening of the eligible studies, the extraction of data of interest, and the quality assessment of the included studies will all be independently performed by different members of our team. The primary outcome of this proposed study will be comparing the risk of recurrence or death from cervical cancer and the risk of all-cause death in patients with two different treatments (completion of radical hysterectomy or abandonment of radical hysterectomy); the secondary outcome of this proposed study will be comparing the risk of the grade 3/4 toxicities associated with the two types of management. Given the clinical heterogeneity among the included studies, data on outcomes will be pooled by random-effects models. Heterogeneity will be evaluated using the I2 statistic. The risk of bias for the included studies will be evaluated using the Newcastle-Ottawa Scale or the Cochrane collaboration’s tool. The grade of evidence will be evaluated by two independent members of our team using the Grading of Recommendations, Assessment, Development and Evaluations approach.Ethics and disseminationEthical approval is not required because there will no primary data collected. The findings of this proposed study will be published in an international peer-reviewed journal.PROSPERO registration numberCRD42021273527.

Along with definite clinical effects, traditional Chinese medicine (TCM) has increasingly gained worldwide attention. Quality control marker (Q-marker) is always used to confirm the primary effects of herbs or TCM. Thus, the characterization of the metabolism features and subsequently induced effects are essential to reveal the functional consequences. In this work, a strategy by integrating metabolite profiling of a Q-marker and network pharmacology was proposed and applied to explore the potential function of herbs, and prim-O-glucosylcimifugin, the Q-marker of Radix Saposhnikoviae, was used as an example. As a result, 35 metabolites were characterized in rats' plasma, urine, feces, heart, liver, spleen, lung, kidney, and brain. Among them, M13/M17/M20/M23/M24/M28 were the primary metabolites, and 23 metabolites were reported for the first time. It was found that major metabolic pathways of prim-O-glucosylcimifugin were hydroxylation, dehydrogenation, hydrogenation and glucuronidation. In addition to the above metabolic reactions, methylation, hydrogenation, glycosylation, isomerization, sulfation, and other S-conjunctions were found in prim-O-glucosylcimifugin for the first time. Meanwhile, targets of prim-O-glucosylcimifugin and its major metabolites targeted additional 125 targets with functions of MAPK signaling pathway, proteoglycans in cancer, pathways in cancer, bladder cancer, colorectal cancer, serotonergic synapse and natural killer cell-mediated cytotoxicity. Among them, the depression of inflammation by MAPK signaling pathway might be the core mechanism for prim-O-glucosylcimifugin to treat respiratory tract infections. The above results provided vital information for understanding the metabolism and functional mechanism of prim-O-glucosylcimifugin in the treatment of respiratory tract infections, and a new insight for revealing the pharmacological mechanism of the complex system was also provided.

Food additives are widely used in our daily life, and the side-effects caused by them have gained extensive attention around the world. Notably, constituent-oriented metabolites, in some sense, always contribute to pharmacological changes, inducing toxicity, therapeutic effects, etc. Characterization of the metabolites and their potential functions is of great importance to the practical applications. In this work, an integrated strategy by combining metabolite profiling and network pharmacology was applied to characterize the metabolic features and reveal pharmacological changes of neohesperidin dihydrochalcone (NHDC) in vivo to demonstrate its pharmacological mechanism and potential functions. As a result, a total of 19 metabolites (3 in plasma, 19 in urine, 8 in feces, 3 in heart, 5 in liver, 0 in spleen, 1 in lung, 2 in kidneys and 2 in brain) were screened and 18 of them were characterized for the first time. Phase I metabolic reactions of hydrolysis and phase II reactions of glucuronidation, sulfation, glutamylation, N-butyryl glycylation and lactylation were the main metabolic reactions of NHDC in vivo. Moreover, the results analyzed by network pharmacology revealed that, in addition to common pathways (steroid hormone biosynthesis) of NHDC, metabolites' targets were involved in pathways in cancer, ovarian steroidogenesis, proteoglycans in cancer, PI3K-Akt signaling pathway and progesterone-mediated oocyte maturation, indicating that these functional changes might result in potential novel functions or other side-effects, such as a disorder of steroid hormones. Our work provided the metabolic features and functional modifications of NHDC in vivo for the first time, and meaningful information for further pharmacological validations or potential functions is supplied.

Elucidating the therapeutical basis and functional mechanism of traditional Chinese medicine (TCM) is still a challenge faced by researchers since the effects of TCM are always achieved by the interactions of multiple components and multiple targets. In this study, an integrated strategy using a combination of chemical profiling, network pharmacology and in vitro experimental validation was applied to profile the trace constituents of TCM and characterize their functional mechanism, and Rhizoma coptidis (RC) was used as an example. As a result, a total of 55 compounds were identified or tentatively characterized in the water extract of RC, including 22 organic acids, 17 alkaloids, 8 lignans, 2 flavonoids, 4 phenylethanoid glycosides, and 2 other types of compounds. Meanwhile, a potential novel compound (compound 41) – one of the alkaloids – was found and characterized. Notably, organic acids in RC were systematically characterized for the first time. Moreover, the pharmacological targets of the 46 main constituents of RC were predicted using the network pharmacological method, and 234 of them were involved in diabetes mellitus (DM). KEGG analysis indicated that the Rap1 signaling pathway, the cAMP signaling pathway, the PI3K–Akt signaling pathway, and inflammatory mediator regulation of TRP channels were the core signaling pathways for RC in the treatment of DM. Further, the anti-inflammatory effects of RC, correlated with inflammatory mediator regulation of TRP channels, were confirmed by using the LPS-induced RAW 264.7 cell model. Meanwhile, the downstream pathway (NF-kB) of TRP channels was validated by western blot. Our work comprehensively provided the material basis and potential pharmacological mechanism of RC against inflammation in DM; in the meantime, a new insight for elucidating the functional mechanism of TCM was also supplied.

Previous studies examining the incidence of omental metastasis in uterine serous carcinoma generally suffered from small sample size, retrospective observational design, and single-center setting. So far, there was no systematic review and meta-analysis available on this topic, we conducted this study to quantitatively synthesize the data relating to this topic.systematic review and meta-analysis.PubMed, Embase, and Web of Science were searched up until August 15, 2020. Two reviewers independently performed study selection, data extraction, and quality assessment. Iincidence of omental metastasis in uterine serous carcinoma.A total of 16 studies involving 1012 women with uterine serous carcinoma were included in this study. All the included studies were at low risk of bias, and the heterogeneity among them was low. The pooled incidence of overall omental metastasis, occult omental metastasis, and gross omental metastasis in uterine serous carcinoma were 18% (95% CI, 0.15-0.20), 6% (95% CI, 0.04-0.08), and 10% (95% CI, 0.08-0.13), respectively.Uterine serous carcinoma has a high tendency of omental metastasis. The main form of omentum involvement is gross metastasis. However, occult metastasis in the normal-looking omentum is also worthy of note.

RATIONALE Salvianolic acid B (Sal B), the Q-marker in Salvia miltiorrhiza, was proved to present an obvious anti-diabetes effect when treating as a food intake. Till now, its metabolism feature, tissue distribution, and anti-diabetes mechanism of Sal B were not fully elucidated. METHODS The metabolites of Sal B in rats were profiled by an ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method. The potential anti-diabetes mechanism of Sal B was predicted by network pharmacology. RESULTS A total of 31 metabolites were characterized in rats after ingestion of Sal B at a dosage of 40 mg/kg, including 1 in plasma, 19 in urine, 31 in feces, 0 in heart, 0 in liver, 0 in spleen, 1 in lung, 1 in kidney and 0 in brain. Among them, 18 metabolites were reported for the first time. Phase I reactions of hydrolysis, hydrogenation, dehydroxylation, hydroxylation, decarboxylation, isomerization, and phase II reactions of methylation were found in Sal B. Notably, decarboxylation and dehydroxylation were revealed in salvianolic acid B for the first time. The pharmacology network results showed that Sal B and its metabolites could regulate ALB, PLG, ACE, CASP3, MMP9, MMP2, and MTOR, etc. The above targets were involved in insulin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway, etc. CONCLUSION: The metabolism feature of Sal B in vivo was systematically revealed, and its anti-diabetes mechanism for further pharmacological validations was predicted based on metabolite profiling and network pharmacology for the first time.

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Rationale Traditional Chinese medicines (TCMs) attract worldwide attention because of their effects in clinical application recorded in China historical ancient codes and in records, such as 'Treatise on Febrile Diseases'. With the developments of drug analysis and research, evaluating the in vivo substances in TCMs has become of great importance. Scutellariae Radix (SR, named as huang-qing in China), the root of Scutellaria baicalensis Georgi, has shown favorable clinical effects and safety in the treatment of infection diseases; however, its in vivo compounds are unclear and need detailed investigation. Methods An ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF MS) method coupled to an integrated strategy involving diagnostic ions, neutral losses and a prediction platform was used to explore the constituents of SR, and their exogenous substances in rats. Results A total of 118 chemical constituents mainly featuring five chemical structure types (flavone C-glycosides, flavone O-glycosides, free flavones, flavanones and phenylethanoid glycosides) were identified or tentatively characterized in SR, and 175 xenobiotics (68 prototypes and 107 metabolites) were profiled in rat plasma, urine, bile and feces after ingestion of SR. The metabolites were classified into four related chemical groups: flavone C-glycosides, flavone O-glycosides, flavanones and phenylethanoid glycosides. Phase II metabolism reactions, such as glucuronidation and sulfation, were the major metabolic reactions in addition to phase I reactions of hydrolysis and hydrogenation. The corresponding main metabolic features of SR in rats were also elucidated. Conclusions The metabolism of SR, as a whole, was systemically revealed for the first time, and our work also provided meaningful information for pharmacokinetics studies and pharmacological analysis of SR in future work.

Lonicerae japonicae flos.(LJF) was widely used as a drug to treat upper respiratory tract infection or a tea to clear heat in Asian countries for thousands of years. Despite of its curative effects confirmed by modern pharmacological methods, its functional materials and mechanism against influenza were still unclear and needed further investigation. In this study, an integrated strategy based on in vivo substances profiling and network pharmacology was proposed and applied to screen out the potential anti-influenza substances and mechanism of LJF. An UHPLC/Q-TOF MS method was utilized to profile the chemical components in LJF and their metabolites in rats. The targets of absorbed prototypes were predicted by Swiss Target Prediction, and they were further analyzed by String and Kyoto Encyclopedia of Genes and Genomes (KEGG). As a result, a total of 126 chemical components mainly featuring three chemical structure types were characterized, including 70 iridoid glycosides, 17 caffeoylquinic acids, 24 flavonoids, and 15 other types compounds. Among them, ten N-contained iridoid glycosides were characterized as potential novel compounds. Moreover, 141 xenobiotics (74 prototypes and 67 metabolites) were clearly screened out in rat plasma and urine after ingestion of LJF. Phase II reactions (sulfation, glucuronidation, methylation) and phase I reactions (dehydroxylation, hydrogenation, hydrolysis, N-heterocyclization) were the main metabolic reactions of LJF in rats. Further, a total of 338 targets were predicted and TNF, PTGS2 and EGFR were the three main targets involved in the pathology of influenza. In addition to normal NF-κB pathway, T cell signal pathway and mTOR signal pathway were the other patterns for LJF to achieve its anti-flu effects. Our work provided the meaningful data for further pharmacological validation of LJF against influenza, and a new strategy was also proposed for minimizing the process to reveal the mechanism and functional basis of TCMs.

Traditional Chinese medicine was widely used in China since its definite effects and therapy. The components of TCM were absorbed into the circle system as the format of prototypes or metabolites, which contributed to the therapy or side effects. Declaring the functional changes in this process was of great importance to the clinical applications. In this work, an integrated strategy based on metabolites’ profiling and network pharmacology was proposed for exploring the pharmacological changes of compounds in vivo. Arctiin, the main component in Fructus Arctii with various kinds of bioactivities, was used as an example. An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry and metabolynx™ software was applied to characterize the metabolites of arctiin in rats at a dosage of 100 mg/kg; network pharmacology was applied to characterize the functional changes. As a result, fifty-three metabolites (32 in plasma, 40 in urine, 19 in bile, 20 in feces, 1 in brain, 12 in liver and 4 in lungs) were screened out and characterized, and 3 of them were unambitiously identified by comparison with standard substances. Among them, 38 metabolites were reported for the first time. It was found the major metabolic pathways of arctiin in rats were demethylation, lactone-opening and phase II conjugations with sulfate and glucuronide. It also confirmed that M14, M15, M18, M23, M22, M43 and M45 were the major circulating forms of arctiin in rats following oral administration. In addition to the above metabolic reactions, phase I reactions of hydrolysis, demethylation, dehydroxylation were also observed, and dehydrogenation were first revealed metabolic patterns of arctiin in rats. Meanwhile, in addition to the main targets of arctiin (MTOR, EGFR and MAPK14), its metabolites targeted additional 392 targets with additional functions of anti-hepatitis B or viral carcinogenesis (SRC, CAPS3, PIK3CA, CDK4, ESR1, MMP9 and ERBB2). The above results provided very important information for understanding the metabolism and functional changes of arctiin in vivo, and supporting data for further pharmacological evaluation. Our work also provided a newsight for elucidation of functional changes of TCMs in vivo.

The present study was to investigate the protective and immunomodulatory effectiveness of Macleaya cordata extract in reducing the deleterious effects of Aeromonas hydrophila (A. hydrophila) on vital immune organs in Misgurnus anguillicaudatus (M. anguillicaudatus). A fish-specific TLR20 homologue was characterized (named as MaTLR20) and had the closest evolutionary relationship with TLR20 from Cyprinus carpio and Ctenopharyngodon idella. MaTLR20 was ubiquitously expressed, especially in the spleen. Following A. hydrophila challenge, MaTLR20 and the proinflammatory cytokines (IL-1β, IL-8, TNF-α, IFN-γ) were significantly affected, and histomorphological changes in the spleen were seen. Experiments revealed that the M. cordata extract had the capability of inhibiting bacteria amplification in vitro and suppressing the expression of proinflammatory cytokines in vivo. The histopathological test revealed that M. cordata extract can ameliorate spleen injury in M. anguillicaudatus challenged by A. hydrophila. These results suggested that the M. cordata extract can promote immunological status by inhibiting immune-related gene expression to reduce excessive inflammation and improving histopathological morphological integrity in damaged spleens against A. hydrophila infection.

Visible light-driven azidation of vinyl arenes with azidobenziodoxole as the azidating agent was investigated in acetonitrile by using Cu(I)(phenanthroline)2 complex [Cu(dap)2]PF6 as photocatalyst....

In this paper, finite element software ANSYS is used in thermo-fluid-solid coupling analysis for helical transferring tube of SG in SMART reactor by using finite element method, The resulting heat flux, temperature field, stress and strain of the pipe are calculated, It is found that the stress, the maximum value of strain and deformation produced outside tube depend strongly on the temperature of the system.

To understand the adaptive strategies of the overwintering adults of Steno- catantops splendens, the mechanism of maintenance and termination of the reproductive diapause, the variation in mortality between overwintering females and males, and the mating strategy of the males were investigated. The results indicated that the adult repro- ductive diapause in natural conditions was mainly regulated by photoperiod in the fall - long photoperiods promoted reproductive development and short photoperiods maintained reproductive diapause, and the sensitivity of the overwintering adults to photoperiod was over before the end of the winter. When transferred from natural conditions to controlled laboratory conditions on dates from September through February, pre-oviposition became increasingly shorter with increasingly deferred transfer dates regardless of photoperiod conditions. The adults treated with low temperature for 30 days in September through November had significantly shorter pre-oviposition, suggesting that low temperatures in winter had an important role in the termination of reproductive diapause. The female had a significantly lower supercooling point than the male, which was related to their lower mortality after winter. In addition, observations of wild populations of the species indicated that mating behavior prior to winter and the duration of pre-mating period were not affected by photoperiod; mating and sperm transfer were mostly completed by November. Compared with females only mating before winter, females mating in the spring had shorter life span, longer pre-oviposition, lower hatching rate and laid fewer egg pods while showing no significant difference with regard to ovipositional interval, per pod number of eggs and nymph dry weight.

In order to recycle regenerative braking energy, we built the PHEV regenerative braking test platform with model design concept, based on the parallel hybrid structure. We proposed a regenerative braking control strategy under parallel braking force distribution, and established the mathematical models for main elements of the platform. In order to confirm the performance and the operational reliability of the platform, simulation models of the regenerative braking system were built in MATLAB/Simulink by combining the test data with mathematic models. We chose universal NEDC drive cycles for simulation, and the results indicated that the regenerative braking energy was effectively recycled. The structure and control strategy of regenerative braking test platform was proved to be rational.

To understand the adaptive strategies of the overwintering adults of Stenocatantops splendens, the mechanism of maintenance and termination of the reproductive diapause, the variation in mortality between overwintering females and males, and the mating strategy of the males were investigated. The results indicated that the adult reproductive diapause in natural conditions was mainly regulated by photoperiod in the fall - long photoperiods promoted reproductive development and short photoperiods maintained reproductive diapause, and the sensitivity of the overwintering adults to photoperiod was over before the end of the winter. When transferred from natural conditions to controlled laboratory conditions on dates from September through February, pre-oviposition became increasingly shorter with increasingly deferred transfer dates regardless of photoperiod conditions. The adults treated with low temperature for 30 days in September through November had significantly shorter pre-oviposition, suggesting that low temperatures in winter had an important role in the termination of reproductive diapause. The female had a significantly lower supercooling point than the male, which was related to their lower mortality after winter. In addition, observations of wild populations of the species indicated that mating behavior prior to winter and the duration of pre-mating period were not affected by photoperiod; mating and sperm transfer were mostly completed by November. Compared with females only mating before winter, females mating in the spring had shorter life span, longer pre-oviposition, lower hatching rate and laid fewer egg pods while showing no significant difference with regard to ovipositional interval, per pod number of eggs and nymph dry weight.

The issue of robustness assessment for progressive collapse of structures has been paid much attention to in the community of civil engineering since the 9/11 event. In this paper, both deterministic indices and reliability-based indices are introduced to quantify the robustness of a structure. The conventional deterministic pushdown analysis is improved to take into account the loading scheme for simulating column loss. To consider stochastic system properties, a random pushdown analysis is proposed by an improved point estimation method based on Nataf transformation. By using the developed pushdown methods, the reserve load carrying capacity of the damaged structure is evaluated, the robustness for resisting progressive collapse of the damaged structure is quantitatively assessed and the key element to be removed which is critical to structural global performance is identified. A code-conforming reinforced concrete frame structure is taken as a case study to demonstrate the applicability of the newly developed methods.