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Most of the reported work focus on the development of O-, N-, C- and S-glycosylation methods. However, no study explores P(III)-glycosylation reaction. Herein we describe a convenient protocol to realize P(III)-glycosylation process. A simple β-phosphino ester is adopted as P(III)-transfer reagent for this new type of glycosylation via a nucleophilic substitution and release strategy. Diverse phosphine units are introduced to the anomeric center of various sugars efficiently and with excellent stereoselectivity. The value of this method is showcased by the prepared P(III)-sugars as novel linkers in bioactive molecule conjugation, new chiral ligands in metal-catalyzed asymmetric allylic substitutions and organocatalysts. Preliminary mechanistic studies corroborated the designed P(III)-transfer process., (© 2024 Wiley-VCH GmbH.)

Different from the reported work focusing on the construction of single P- or C-stereocenter via hydrophosphinylation of unsaturated carbon bonds, the highly diastereo- and enantioselective hydrophosphinylation reaction of allenes, conjugated enynes and 1,3-dienes is achieved via a designed Pd/Co dual catalysis and newly modified masked phosphinylating reagent. A series of allyl motifs bearing both a tertiary C- and P-stereocenter are prepared in generally good yields, >20 : 1 dr, >20 : 1 rr and 99 % ee. The unprecedented diastereo- and enantioselective hydrophosphinylation of 1,3-enynes is established to generate skeletons containing both a P-stereocenter and a nonadjacent chiral axis. The first stereodivergent hydrophosphinylation reaction is also developed to achieve all four P-containing stereoisomers. The present protocol features the use of only 3-minutes reaction time and 0.1 % catalyst, and with the observation of up to 730 TON. A set of mechanistic studies reveal the necessity and roles of two metal catalysts and corroborate the designed synergistic process., (© 2024 Wiley-VCH GmbH.)

The asymmetric functionalization of unstrained C(sp 3 )-C(sp 3 ) bonds could be a powerful strategy to stereoselectively reconstruct the backbone of an organic compound, but such reactions are rare. Although allylic substitutions have been used frequently to construct C-C bonds by the cleavage of more reactive C-X bonds (X is usually an O atom of an ester) by transition metals, the reverse process that involves the replacement of a C-C bond with a C-heteroatom bond is rare and generally considered thermodynamically unfavorable. We show that an unstrained, inert allylic C-C σ bond can be converted to a C-N bond stereoselectively via a designed solubility-control strategy, which makes the thermodynamically unfavorable process possible. The C-C bond amination occurs with a range of amine nucleophiles and cleaves multiple classes of alkyl C-C bonds in good yields with high enantioselectivity. A novel resolution strategy is also reported that transforms racemic allylic amines to the corresponding optically active allylic amine by the sequential conversion of a C-N bond to a C-C bond and back to a C-N bond. Mechanistic studies show that formation of the C-N bond is the rate-limiting step and is driven by the low solubility of the salt formed from the cleaved alkyl group in a nonpolar solvent.

Background: This study aimed at investigating the relationship between the weekend catch-up outdoor duration (WCOD) and prevalence of myopia among students in China., Methods: This cross-sectional study recruited participants in 107 schools (six cities, 30 districts) from China from May to June 2021. Demographic characteristics (age, grade, sex, ethnicity, BMI, resident, and parents' myopia), optically habits (bad writing habits, working/studying time per day, continuous working/studying time per day, and screen time per day) and outdoor duration (weekday and weekend) were obtained from questionnaire. WCOD was defined as outdoor time 1 h longer on weekends than on weekdays. Spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Adjusted multivariate logistic regression analysis was performed to evaluate the relationship between WCOD and prevalence of myopia., Results: Students with myopia had shorter WCOD compared with those without myopia (P < 0.001). Adjusted multivariate logistic regression analyses showed negative associations between WCOD and prevalence of myopia in Chinese students, especially in students with WCOD of 2-3 h (OR = 0.577, P < 0.001) and 3-4 h (OR = 0.571, P = 0.004) when the weekday outdoor duration was 0.5-1 h, as well as students with WCOD of 2-3 h (OR = 0.614, P = 0.003) when the weekday outdoor duration was 1-2 h. Similar results were observed in students with high myopia. Students with high myopia had shorter WCOD compared with those without high myopia (P = 0.001). Negative associations between WCOD and prevalence of high myopia were significant in students with WCOD of 1-2 h when the weekday outdoor duration was < 0.5 h (OR = 0.585, P = 0.007) and 0.5-1 h (OR = 0.537, P = 0.018)., Conclusion: Our study, for the first time, reported that a WCOD have a potential to reduce the prevalence of myopia and high myopia in Chinese students., (© 2024. The Author(s).)

An unprecedented 1,5-addition/N-1,4-addition cascade reaction is established via palladium hydride catalysis. A variety of polysubstituted dihydropyrrole skeletons are constructed in high yield and with exclusively >20 : 1 diastereoselectivity. An enantioselective protocol of this design is also developed to provide a novel access to enantioenriched dihydropyrroles., (© 2024 Wiley-VCH GmbH.)

The unprecedented copper-catalyzed asymmetric alkynylallylic monofluoroalkylation reaction is described via the use of 1,3-enynes and fluorinated malonates. A series of 1,4-enynes bearing a monofluoroalkyl unit are achieved in high yields, excellent regio- and enantioselectivity and high E/Z selectivity. The asymmetric propargylic monofluoroalkylation is also developed. The reliability and synthetic value of the work are highlighted by a gram-scale test and a couple of downstream transformations. Preliminary mechanistic studies unveil a negative nonlinear effect for the catalytic process.

Different from electronically matched 1,4- and 1,6-additions, herein, we disclose an electronically mismatched 1,5-conjugate addition process with oximes as the nucleophiles. By this design, the oxime moieties are readily introduced to the γ-position of the electron-deficient substrates in good yields, excellent regioselectivities, and high enantioselectivities. The corresponding allyl oximes are also conveniently transformed into a series of valuable enantioenriched skeletons.

Catalytic asymmetric transformations by dearomatization have developed into a widely applicable synthetic strategy, but heavily relied on the use of arenes bearing a heteroatom. In this case, the dearomatization is facilitated by the involvement of a p-orbital electron of the heteroatom. Different from the conventional substrate-dependent model, here we demonstrate that the activation by a d-orbital electron of the transition-metal center can serve as a driving force for dearomatization, and is applied to the development of a novel asymmetric alkynyl copper facilitated remote substitution reaction. A newly modified PyBox chiral ligand enables the construction of valuable diarylmethyl and triarylmethyl skeletons in high enantioselectivities. An unexpected tandem process involving sequential remote substitution/cyclization/1,5-H shift leads to the formation of the enantioenriched C-N axis. A gram-scale reaction and various downstream transformations highlight the robustness of this method and the potential transformations of the products. Preliminary mechanistic studies reveal a mononuclear Cu-catalyzed remote substitution process., (© 2023 Wiley-VCH GmbH.)

Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ 3 substitution have emerged as a reliable method to construct stereogenic centers, and mainly rely on the use of heteroatom-based or carbon nucleophiles bearing acidic C-H bonds. In comparison, sp 2 carbon nucleophiles are generally not under consideration because of enormous challenges in cleaving corresponding inert sp 2 C-H bonds. Here, we report a protocol to achieve asymmetric formal sp 2 hydrocarbonations, including hydroalkenylation, hydroallenylation and hydroketenimination of both 1,3-dienes and alkynes via hydroalkylation and Wittig reaction cascade. A series of unachievable motifs via hydrofunctionalizations, such as di-, tri- and tetra-substituted alkenes, di-, tri- and tetra-substituted allenes, and tri-substituted ketenimines in allyl skeletons are all facilely constructed in high regio-, diastereo- and enantioselectivities with this cascade design. Stereodivergent synthesis of all four stereoisomers of 1,4-diene bearing a stereocenter and Z/E-controllable olefin unit highlights the power of present protocol. An interesting mechanistic feature is revealed that alkyne actually undergoes hydrocarbonation via the formation of conjugated diene intermediate, different from conventional viewpoint that the hydrofunctionalization of alkynes only involves allene species., (© 2023. Springer Nature Limited.)

Chain walking has been an efficient route to realize the functionalization of inert C(sp 3 )-H bonds, but this strategy is limited to mono-olefin migration and functionalization. Herein, we demonstrate the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation for the first time. The adoption of palladium hydride catalysis and secondary amine morpholine as solvent is critical for achieving high substrate compatibility and stereochemical control with this method. The protocol is also applicable to the functionalization of three vicinal C(sp 3 )-H bonds and thus construct three continuous stereocenters along a propylidene moiety via a short synthetic process. Preliminary mechanistic experiments corroborated the design of simultaneous walking of remote dienes., (© 2023 Wiley-VCH Verlag GmbH.)

Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing a remote leaving group is scarcely viewed as a potential allylation substrate. Herein, we describe feasible protocols to achieve regiodivergent allylic C-H functionalizations via palladium-catalyzed remote substitution, which provides a novel strategy for the seldomly studied migratory Tsuji-Trost reaction. Dictated by a suitable ligand, a process that involved 4,3-hydrofunctionalization of the generated conjugated diene intermediate via metal walking is observed in generally >20 : 1 regioselectivity. Unexpectedly, a related 1,4-hydrofunctionalization pathway is found to be a major route with a newly synthesized electron-rich bisphosphine ligand, which challenges the conventional viewpoint on the potential regioselectivity of hydrofunctionalizations of linear internal conjugated dienes via η 3 -substitution. A series of deuterium experiments and kinetic studies provide a preliminary insight into the potential catalytic cycle., (© 2023 Wiley-VCH GmbH.)

The appropriate sizes of scale-breeding industries are causing increasing attention in that rational scale-breeding industries may both meet the meat demand of the market and avoid serious environmental problems. In this paper, the appropriate scales of breeding-type family farms were studied from the perspective of quantifying resource losses. The mathematical models about quantifying resource losses were built, and then the evaluation index system of resource losses was established. More than one hundred family farms in Sichuan province and Chongqing city of China located in the subtropics were selected as research cases and were classified as small-, medium- and large-scale family farms, whose unit resource losses and resource loss rates were both evaluated by the index system. Results show that the unit resource losses and the resource loss rate of medium-scale family farms are the lowest among these three kinds of family farms. Therefore, medium-scale farms are moderate, and then are recommended for scale-breeding industries. Implications : Appropriate sizes are essential for the green development of scale-breeding industries. The external environment factors and internal resource effect should be considered. The unit resource losses and the resource loss rate of medium-scale family farms are the lowest among these three kinds of family farms. Therefore, medium-scale farms are optimistic, and then are recommended for scale-breeding industries. For medium-scale family farms, the scale of 800-999 pigs is optimistic. Furthermore, it is very necessary to adopt green cycle.

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit in synthetic chemistry. Abundant applications of free enantioenriched allyl alcohol and allyl hydroxylamine motifs have made the asymmetric hydration and hydroaminoxylation of conjugated dienes from water and hydroxylamine, respectively, intriguing and efficient routes that have, however, been unachievable thus far. A fundamental challenge is the failure to realize transition-metal-catalyzed enantioselective C-O bond constructions via hydrofunctionalization of conjugated dienes. Here, we perform a comprehensive study toward the stereoselective formal hydration and hydroaminoxylation of conjugated dienes by synthesizing a set of new P,N-ligands and identifying an aryl-derived oxime as a surrogate for both water and hydroxylamine. Asymmetric hydroalkoxylation with new P,N-ligands is also elucidated. Furthermore, versatile derivatizations following hydration provide indirect but concise routes to formal hydrophenoxylation, hydrofluoroalkoxylation, and hydrocarboxylation of conjugated dienes that have been unreported thus far. Finally, a ligand-to-ligand hydrogen transfer process is proposed based on the results of preliminary mechanistic experiments.

Electronically matched nucleophilic 1,6-conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5-conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5-conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5-conjugate reaction, followed by inter- or intramolecular [3+2] cyclization. A migratory 1,5-addition protocol is established to corroborate the feasibility of this umpolung concept. The 1,5-addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis., (© 2022 Wiley-VCH GmbH.)

Objective: This study aims to compare the characteristics of dysphagia among different lesion sites and explore the possible risk factors that are relevant to penetration and aspiration after stroke., Materials and Methods: Data on patients with post-stroke dysphagia were collected. Major measures of the videofluoroscopic swallowing study included pharyngeal transit duration (PTD), pharyngeal response duration (PRD), soft palate elevation duration (SED), stage transition duration (STD), hyoid bone anterior-horizontal displacement (HAD), hyoid bone superior-horizontal displacement (HSD), upper esophageal sphincter opening (UESO), Pharyngeal Residual Grade (PRG), and Penetration Aspiration Scale (PAS). Included patients were divided into supratentorial (deep or lobar intracerebral) and infratentorial stroke groups. The Kruskal-Wallis test, Spearman's correlation analysis, and multivariate logistic regression analyses were used to test the difference and the correlation between those measures. Time-to-event endpoints (oral feeding) were analyzed by the Kaplan-Meier method., Results: A total of 75 patients were included in this study. Significant differences were demonstrated in PTD, PRD, SED, STD, HAD, HSD, UESO, PAS, and PRG between supratentorial and infratentorial stroke groups ( p < 0.05). The PRG score of the lobar intracerebral subgroup was significantly higher ( p < 0.05) than that of the deep intracerebral and lobar + deep intracerebral stroke subgroups, while HSD was significantly shorter ( p < 0.01). Spearman's correlation analysis revealed that PAS was related to PTD, PRG, HAD, and UESO ( p < 0.05). Multivariate logistic regression analysis demonstrated that HAD and PRG may be risk factors for penetration and aspiration ( p < 0.05). Kaplan-Meier survival plot showed that there was a significant difference in time to oral feeding between supratentorial and infratentorial stroke groups ( p < 0.01)., Conclusion: Infratentorial stroke may lead to worse swallowing function as compared with supratentorial stroke, and lobar intracerebral stroke may be worse than deep intracerebral stroke. Suitable preventive measures may be considered for patients with higher PRG scores and shorter HSD to avoid penetration and aspiration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiao, Wu, Ye, Dai, Dai, He and Dou.)

A novel protocol is established for the long-standing challenge of stereoselective geminal bisglycosylations of saccharides. The merger of PPh 3 as a traceless glycosidic leaving group and 1,2-boronate migration enables the simultaneous introduction of C-C and C-B bonds at the anomeric stereogenic center of furanoses and pyranoses. The power of this method is showcased by a set of site-selective modifications of glycosylation products for the construction of bioactive conjugates and skeletons. A scarce metal-free 1,1-difunctionalization process of alkenes is also concomitantly demonstrated.

Objective: To clarify the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on cognitive function in cerebral ischemic rats, and to explore its underlying mechanism by RNA sequencing. Methods: Thirty male Sprague-Dawley (SD) rats underwent transient middle cerebral artery occlusion (tMCAO). According to the Bederson score, 10 rats with a score of 1-3 were excluded, and the remaining 20 rats were then randomly divided into the tMCAO group ( n =10) and the rTMS group ( n =10). Meanwhile, 10 rats with sham operation were assigned to the sham group ( n =10). Rats in the rTMS group received 20 Hz rTMS from day 7 to day 28 after surgery. From day 28 to day 33 after the operation, Morris water maze test was performed to detect the cognitive function of rats in each group. The cortical tissues around the infarcts from the rTMS tMCAO groups were taken for RNA sequencing analysis, with 3 rats in each group. Results: The escape latency of rats in the rTMS group[ (53±4)s] and the group [(51±5)s] were significantly shorter than that of the tMCAO group[ (58±4)s, P <0.05)]. The times that the rats crossed the original platform in 60 seconds in the rTMS group[2.5 (1.5-3.0)] and sham group[3.0 (1.5-3.0)] were more than that of the tMCAO group [1.0(0.5-1.5)] ( P <0.05). RNA sequencing detected 16 significantly differentially expressed genes, including 9 up-regulated genes and 7 down-regulated genes. GO analysis showed that the functions of up-regulated genes were mainly concentrated in the processes of chemical homeostasis and cell metal ion homeostasis. While the functions of down-regulated genes mainly enriched in the inflammatory response. Conclusion: Twenty Hz rTMS can improve the cognitive function of rats with cerebral infarction, and its underlying mechanism may be related to maintaining chemical and metal ion homeostasis and regulating the polarization of microglia to reduce neuroinflammation.

Transition metal-catalyzed asymmetric allylic substitution with a suitably pre-stored leaving group in the substrate is widely used in organic synthesis. In contrast, the enantioselective allylic C(sp 3 )-H functionalization is more straightforward but far less explored. Here we report a catalytic protocol for the long-standing challenging enantioselective allylic C(sp 3 )-H functionalization. Through palladium hydride-catalyzed chain-walking and allylic substitution, allylic C-H functionalization of a wide range of acyclic nonconjugated dienes is achieved in high yields (up to 93% yield), high enantioselectivities (up to 98:2 er), and with 100% atom efficiency. Exploring the reactivity of substrates with varying pK a values uncovers a reasonable scope of nucleophiles and potential factors controlling the reaction. A set of efficient downstream transformations to enantiopure skeletons showcase the practical value of the methodology. Mechanistic experiments corroborate the PdH-catalyzed asymmetric migratory allylic substitution process., (© 2021. The Author(s).)

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

Engraulis japonicus , an important fishery resource, is a key species in ecosystem trophodynamics studies. In this study, we examined stomach content of E. japonicusby stable isotope analyses, with samples collected from the East China Sea in 2008-2009 and 2020. The aim of this study was to demonstrate their diet composition, diel and ontogenetic changes in feeding habits and trophic level. Results of the stomach content analysis showed that E. japonicus mainly fed on planktonic crustaceans and small fish. The main prey species were Euphausia pacifica [index of relative importance (IRI)=87.6%; frequency( F )=57.6%], Paracalanus parvus (IRI=3.2%, F =15.3%), and Themisto gracilipes (IRI=2.1%, F =13.1%). Results of the stable isotope analysis showed that Copepoda were the main food source of E. japonicus , followed by Euphausiacea, and the contribution rate of Amphipoda was the least, which was less than 1%. There was significant diel change in diet composition. Feeding intensity was higher in the daytime than at night, with the highest in the dusk and the lowest at midnight. Ontogenetic change in feeding habit occurred when fork length reached 90 mm, over which the fish fed both zooplankton and small fishes. The δ 13 C of E. japonicus was between -21.66‰ and -18.14‰, with an average of (-19.92±0.86)‰. The δ 15 N of E. japonicus ranged from 4.07‰ to 10.78‰, with an average of (8.14±2.48)‰. Both δ 13 C and δ 15 N values were positively correlated with fork length. Trophic level of the fish was 3.4 with stomach content analysis and 2.7 with stable isotope analysis. The results would provide important reference for understanding nutritional status of pelagic small fish, and offer some basic data to establish ecopath model.

Herein we describe a protocol for the unprecedented stereodivergent synthesis of tertiary fluoride-tethered allenes bearing a stereogenic center and stereogenic axis via Cu/Pd synergistic catalysis. A broad scope of conjugated enynes are coupled with various α-fluoroesters in high yields with high diastereoselectivities and generally >99% ee. In addition, the four stereoisomers of the allene products ensure precise access to the corresponding four stereoisomers of the fluorinated hydrofurans via a novel stereodivergent axial-to-central chirality transfer process.

A palladium-catalyzed alkyl C-H borylation with bromide as a traceless directing group is described, providing a convenient approach to access alkyl boronates bearing a β-all-carbon quaternary stereocenter. The protocol features a broad substrate scope, excellent site selectivity, and good functional group tolerance.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

The Cu-catalyzed asymmetric carboboration of cyclohexadienone-tethered allenes has been achieved through regioselective β-borylation of the allenes and subsequent conjugate addition to cyclohexadienones, affording cis -bicyclic frameworks with acceptable yields and high to excellent enantioselectivities. Further conjugate borylation of the carboboration products proved to be a favorable kinetic resolution process, which improved the overall enantioselectivity. Finally, one-pot preparation of highly enantioenriched tricyclo[5.2.2.0 4,9 ]undecanes was developed from the cyclohexadienone-tethered allenes through β-borylation/1,4-addition and subsequent tandem oxidation/intramolecular aldol reaction.

Conjugated trienes are ubiquitous structures in natural products and organic functional molecules. An efficient 1,4-palladium migration/Heck sequence was developed for the highly stereoselective synthesis of trisubstituent 1,3,5-trienes, which were found to undergo easy E/Z isomerization in the presence of light.

Background: Refractory mycoplasma pneumonia (RMPP) is one of the important pathogens of community-acquired pneumonia (CAP) in children. Its treatment is difficult. The aims of this study were to analyze the clinical manifestations, diagnosis, and treatment of 20 cases of RMPP in children in order to provide a reference for the diagnosis and treatment of RMPP., Methods: The clinical data of 20 patients with RMPP admitted to the Pediatrics Department of the First Affiliated Hospital of Guangzhou Medical University in the recent three years were retrospectively analyzed. The clinical data of 36 patients with common mycoplasma pneumonia in the same period were compared. The clinical manifestations, laboratory examinations, and imaging characteristics of RMPP were discussed. Intrapulmonary and extrapulmonary complications and treatment were also analyzed in order to provide assistance in the diagnosis and treatment of RMPP., Results: There were significant differences between the refractory group and the general group in terms of heat duration, hospitalization time, hypoxemia, lung rales, CRP, ESR, PCT, LDH, ALT, PLT, WBC, D dimer and other laboratory examinations, intrapulmonary and extrapulmonary complications, and treatment (all P<0.05). There was no significant difference in the age, sex, and wheezing between the two groups (P>0.05)., Conclusions: Long duration of fever, tachycardia, and lung rale protrusion may be the clinical characteristics of RMPP. Unilateral pulmonary shadow and atelectasis should be paid more attention, which may be a high-risk factor for the development of RMPP. The inflammation index of RMPP cases increased and there were many complications inside and outside the patients' lungs. It was necessary to give enough macrolides to fight the infection by using Glucocorticoid and Intravenous immunoglobulin reasonably while liver, heart, and fiberoptic bronchoscopy was completed to improve the effectiveness of the diagnosis and treatment.

The metabolic reprogramming is an important basis for the development of many tumors, including prostate cancer (PCa). Metabolic changes in many amino acids consist of serine and glycine affect the biological behavior of them. Phospholipase C epsilon (PLCε) plays an important role as an oncogene. However, its role in regulating amino acid metabolism remains unclear. In this study, results found significantly positive correlation between PLCε and Yes-associated protein (YAP) in PCa tissues. LC-MS/MS and GC-MS results further displayed abnormally elevated levels of serine, glycine and its some downstream metabolites in the blood of PCa patients. Secondly, PLCε knockdown can inhibit serine/glycine producing and proliferation of PCa both in vivo and in vitro. Mechanistically, PLCε may affect the serine/glycine metabolism by regulating dephosphorylation and nuclear translocation of YAP. More interestingly, verteporfin (VP, a specific inhibitor of YAP) could effectively enhance the PLCε-depletion induced inhibition of serine/glycine secretion and growth. Overall, this research revealed the possibility of anomalous serine/glycine levels in the blood for the diagnosis of PCa, identified the important role of the PLCε/YAP axis in regulating serine/glycine metabolism, cell proliferation and tumor growth, and suggested the combination of VP with PLCε-depletion may provide a new idea for the treatment of PCa., Competing Interests: None., (AJCR Copyright © 2020.)

Objective: To analyze the clinical effect of Zhuang medicine tendon therapy combined with chiropractic manipulation in treating sacroiliac joint dislocation., Methods: From January 2017 to May 2018, 60 patients with sacroiliac joint dislocation were divided into treatment group and control group according to the order of admission. There were 19 males and 11 females in the treatment group, aged from 23 to 52 (38.97±3.23) years old, with a course of 2 h to 5.1 months, with an average of (2.19±1.12) months. There were 14 males and 16 females in the control group, aged from 26 to 50 (39.07±3.30) years old, with a course of 3 h to 6 months, with an average of(2.41±1.05) months. The treatment group was treated with Zhuang medicine tendon therapy combined with chiropractic manipulation, while the control group was treated with conventional acupuncture and massage. Before treatment, the main clinical symptoms of the patients were lumbosacral pain, posterior superior iliac spine not at the same level and accompanied with dyskinesia. The pelvic separation test and the "4" test were positive. After treatment, the curative effect was evaluated according to the improved Macnab standard and the "score of treatment of lumbar diseases"., Results: Sixty patients were followed up for an average of 8 months. At the latest follow-up, the clinical effect of modified Macnab was better in the treatment group than in the control group( P <0.01). After treatment, the treatment group was better than the control group on lumbar function score ( P <0.01)., Conclusions: The treatment of sacroiliac joint dislocation by Zhuang medicine tendon therapy combined with chiropractic manipulation has good clinical effect and is worth further application and development., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Small, strained rings have rigid, defined conformations and unique electronic properties. For these reasons, many groups seek to use these subunits to form biologically active molecules. We report a generally applicable approach to attach small rings to a wide range of aromatic compounds by palladium-catalyzed α-arylation of cyclopropyl, cyclobutyl and azetidinyl esters. The direct α-arylation of cyclopropyl esters and cyclobutyl esters is achieved in high yield by ensuring that the rate of coupling exceeds the rate of Claisen condensation. The α-arylation of azetidines is achieved without ring opening of the strained saturated heterocycle by conducting the reactions with an azetidine derivative bearing a benzyl protecting group on nitrogen. Mechanistic studies show that the α-arylation of small rings is challenging because of the weak acidity of α C-H bond (cyclopropanes), strong sensitivity of the strained esters to Claisen condensation (cyclobutatanes), or facile decomposition of the enolates (azetidinyl esters).

Although much effort has been spent on the enantioselective synthesis of tertiary alkyl fluorides, the synthesis of compounds containing such a stereogenic center within an array of stereocenters, particularly two vicinal ones, remains a synthetic challenge, and no method to control the configuration of each stereogenic center independently has been reported. We describe a strategy to achieve such a stereodivergent synthesis of vicinal stereogenic centers, one containing a fluorine atom, by forming the connecting carbon-carbon bond with a catalyst system comprising an iridium complex that controls the configuration at the electrophilic carbon and a copper catalyst that controls the configuration at the nucleophilic fluorine-containing carbon. These reactions occur with alkyl- and aryl-substituted allylic esters and the unstabilized enolates of azaaryl ketones, esters, and amides in high yield, diastereoselectivity, and enantioselectivity (generally >90% yield, >20:1 dr, 97-99% ee). Access to all four stereoisomers of products demonstrates the precise control of the two configurations independently. This methodology extends to the stereodivergent construction of vicinal quaternary and tertiary stereocenters in similarly high yield and selectivity. DFT calculations uncover the origin of stereoselectivity of copper enolate in allylic substitution.

We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100  TeV. As a result, we observed 24 photonlike events with E>100  TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100  TeV from an astrophysical source.

A novel traceless protecting strategy is presented for the long-standing challenge of conducting the palladium-catalyzed α-arylation of carboxylic aids and secondary amides with aryl halides. Both of the presented coupling processes occur with a variety of carboxylic acids and amides and with a variety of aryl bromides containing a broad range of functional groups, including base-sensitive functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups. Five commercial drugs were prepared through this method in one step in 81-96% yield. Gram-scale synthesis of medication Naproxen and Flurbiprofen with low palladium loading further highlights the practical value of this method.

The enantioselective construction of carbon-heteroatom and carbon-carbon bonds that are alpha to ketones leads to the formation of substructures that are ubiquitous in natural products, pharmaceuticals and agrochemicals. Traditional methods to form such bonds have relied on combining ketone enolates with electrophiles. Reactions with heteroatom-based electrophiles require special reagents in which the heteroatom, which is typically nucleophilic, has been rendered electrophilic by changes to the oxidation state. The resulting products usually require post-synthetic transformations to unveil the functional group in the final desired products. Moreover, different catalytic systems are typically required for the reaction of different electrophiles. Here, we report a strategy for the formal enantioselective α-functionalization of ketones to form products containing a diverse array of substituents at the alpha position with a single catalyst. This strategy involves an unusual reversal of the role of the nucleophile and electrophile to form C-N, C-O, C-S and C-C bonds from a series of masked ketone electrophiles and a wide range of conventional heteroatom and carbon nucleophiles catalysed by a metallacyclic iridium catalyst.

A methyl group on an arene, despite its small size, can have a profound influence on biologically active molecules. Typical methods to form a methylarene involve strong nucleophiles or strong and often toxic electrophiles. We report a strategy for a new, highly efficient, copper and iodide co-catalyzed methylation of aryl- and heteroarylboronic esters with the mild, nontoxic reagent trimethylphosphate, which has not been used previously in coupling reactions. We show that it reacts in all cases tested in yields that are higher than those of analogous copper-catalyzed reactions of MeOTs or MeI. The combination of C-H borylation and this methylation with trimethylphosphate provides a new approach to the functionalization of inert C-H bonds and is illustrated by late-stage methylation of four medicinally active compounds. In addition, reaction on a 200 mmol scale demonstrates reliability of this method. Mechanistic studies show that the reaction occurs by a slow release of methyl iodide by reaction of PO(OMe) 3 with iodide catalyst, rather than the typical direct oxidative addition to a metal center. The low concentration of the reactive electrophile enables selective reaction with an arylcopper intermediate, rather than nucleophilic groups on the arylboronate, and binding of tert-butoxide to the boronate inhibits reaction of the electrophile with the tert-butoxide activator to form methyl ether.

We analyze the Sun's shadow observed with the Tibet-III air shower array and find that the shadow's center deviates northward (southward) from the optical solar disk center in the "away" ("toward") interplanetary magnetic field (IMF) sector. By comparing with numerical simulations based on the solar magnetic field model, we find that the average IMF strength in the away (toward) sector is 1.54±0.21&#95;{stat}±0.20&#95;{syst} (1.62±0.15&#95;{stat}±0.22&#95;{syst}) times larger than the model prediction. These demonstrate that the observed Sun's shadow is a useful tool for the quantitative evaluation of the average solar magnetic field.

A novel terminal olefin-oxazoline ligand was introduced into rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to enones and gave excellent enantioselectivities. The two phenyls proved better than one or three in ligand evaluations.

Objective: To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model., Methods: Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA., Results: Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05)., Conclusions: Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS., (Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

The creation of three consecutive chiral carbon centers in one step is achieved using Cu-catalyzed asymmetric silylative cyclization of cyclohexadienone-tethered allenes. Through regioselective β-silylation of the allene and subsequent enantioselective 1,4-addition to cyclohexadienone, this tandem reaction could afford cis-hydrobenzofuran, cis-hydroindole, and cis-hydroindene frameworks with excellent yields (80-98%) and enantioselectivities (94-98% ee) bearing vinylsilane and enone substructures. Meanwhile, this mild transformation is generally compatible with a wide range of functional groups, which allows further conversion of the bicyclic products to bridged and tricyclic ring structures., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two tunable arylative cyclizations of cyclohexadienone-containing 1,6-enynes are reported via rhodium(III)-catalyzed C-H activation of O-substituted N-hydroxybenzamides. The use of different O substituents, i.e. O-Piv and O-Me, on the directing group allows the formation of either tetracyclic isoquinolones through an Ⓝ-Michael addition process or hydrobenzofurans through a Ⓒ-Michael addition process. Mechanistic investigations of these two cascade reactions clearly indicated that the C-H bond cleavage process was involved in the turnover-limiting step. Furthermore, the cyclization products could be subjected to various transformations for elaborating the pharmaceutically and synthetically valuable potential. This is the first example of a rhodium(III)-catalyzed arylative cyclization reaction of 1,6-enynes, and the results extend the application realm of Cp*Rh(III)-catalyzed C-H activation cascade reactions.

The Cu-catalyzed asymmetric conjugate hydroboration reaction of β-substituted α-dehydroamino acid derivatives has been established, affording enantioenriched syn- and anti-β-boronate-α-amino acid derivatives with excellent combined yields (83-99%, dr ≈ 1:1) and excellent enantioselectivities (92-98% ee). The hydroboration products were expediently converted into valuable β-hydroxy-α-amino acid derivatives, which were widely used in the preparation of chiral drugs and bioactive molecules.

The first Cu-catalyzed asymmetric borylative cyclization of cyclohexadienone-containing 1,6-enynes is achieved through a tandem process: selective β-borylation of propargylic ether and subsequent conjugate addition to cyclohexadienone. The reaction proceeds with excellent regioselectivity and enantioselectivity to afford an optically pure cis-hydrobenzofuran framework bearing alkenylboronate and enone substructures. Furthermore, the resulting bicyclic products could be converted to bridged and tricyclic ring structures. This method extends the realm of Cu-catalyzed asymmetric tandem reactions using bis(pinacolato)diboron (B2pin2).

We report on a clear solar-cycle variation of the Sun’s shadow in the 10 TeV cosmic-ray flux observed by the Tibet air shower array during a full solar cycle from 1996 to 2009. In order to clarify the physical implications of the observed solar cycle variation, we develop numerical simulations of the Sun’s shadow, using the potential field source surface model and the current sheet source surface (CSSS) model for the coronal magnetic field. We find that the intensity deficit in the simulated Sun’s shadow is very sensitive to the coronal magnetic field structure, and the observed variation of the Sun’s shadow is better reproduced by the CSSS model. This is the first successful attempt to evaluate the coronal magnetic field models by using the Sun’s shadow observed in the TeV cosmic-ray flux.

Objective: To analyze the clinical characteristics, image findings, laboratory examination, the therapeutic methods and clinical outcomes of bronchiolitis obliterans (BO) in pediatric patients., Method: Twenty-six pediatric patients with BO were reported. All data were collected from cases who were hospitalized in the Department of Pediatrics, First Affiliated Hospital of Guangzhou Medical College from June 1(st), 2009 to the April 30(th), 2011, and infectious agents, clinical manifestations, risk factors, changes in imageology, laboratory examination, therapeutic methods and treatment responses were analyzed., Result: The ranges of age at onset was 4.5 months-8 years in 26 cases (18 boys and 8 girls). The course of disease was (6.2 ± 3.5) months. The period of followed-up ranged from 2 to 24 months. The common clinical characteristics were persistent wheezing of different severity (26 cases, 100%), cough (24 cases, 92%), intolerance to exercise (22 cases, 85%), short of breath (21 cases, 81%), retraction (20 cases, 77%), wheezy phlegm (16 cases, 62%), keeping with crackles (10 cases, 38%), cyanosis around the mouth (3 cases, 12%) and no clubbed fingers (toes). In 18 cases the etiology was detected, mycoplasma (11 cases, 42%), respiratory syncytial virus (4 cases, 15%), parainfluenza virus (2 cases, 8%), influenza virus A (2 cases, 8%) and influenza virus B (2 cases, 8%), human bocavirus (HBoV) (1 case, 4%). There were 8 cases (31%) with combined infection. Chest X-ray in 10 cases indicated changes suggestive of bronchopneumonia (38%), in only 1 case there was an image of interstitial pneumonia disease (4%). All the patients were diagnosed by high-resolution computerized tomography (HRCT). All cases were demonstrated to have air retention, poor blood perfusion in lung, just like "Westemark sign" with HRCT. In 19 cases antineutrophil cytoplasmic antibody (ANCA) was determined and 10 patients (53%) were positive for P-ANCA, and 8 cases (42%) were positive for C-ANCA. All patients received oral corticosteroid and low doses azithromycin. In 13 cases (50%) the treatment effectively reduced the severity of disease and the frequency of cough and wheezing. The average number of days for symptom improvement was (7.1 ± 4.8) days., Conclusion: Respiratory infection plays an important role in BO in children. The chronic and persistent wheezing, cough, intolerance to exercises, short breath, retraction were the main clinical manifestations. But these symptoms are non-specific. Chest X-ray can not provide enough information for diagnosis. Classical "Westemark sign" with HRCT is an important sign. ANCA with a high positive rate (approximately 50%) suppose immuno-lesion in BO. Oral corticosteroid and methotrexate may relieve clinical symptoms.

The aim of study was to investigate the effect of acute lymphoblastic leukemia (ALL) children bone marrow mesenchymal stem cells (MSC) on resistance of K562/A02 cells and its mechanism. MSC obtained from bone marrow of AL children were cultured and identified. The co-culture of MSC and K562/A02 and the culture of K562/A02 cell suspension alone was performed, of which 2 kinds of cells were treated with same concentration of adriamycin (ADM), and the rate of apoptosis was detected by flow cytometry, bcl-2 and bax of K562/A02 were detected by RT-PCR, while mdr1 gene level was detected by FQ-PCR. The results indicated that the MSC separation and proliferation were viable and steady. The apoptosis rate of the K562/A02 cells co-cultured with MSC was 1.97 ± 0.11%, while apoptosis rate of the K562/A02 cells cultured alone was 8.38 ± 0.29%, there was significant difference (p < 0.05). As compared with the K562/A02 cells cultured alone, the bcl-2 gene expression in K562/A02 cells co-cultured with MSC obviously increased; ratio of bcl-2/bax was obviously enhanced. The mdr1 gene level in K562/A02 co-cultured with MSC was no statistical different from K562/A02 cultured alone (p > 0.05), which suggested that adhesion co-cultured with MSC did not induce mdr1 expression higher than the culture of suspension. It is concluded that the MSC of ALL children can escape the leukemia cells from proapoptotic effect of drugs, the resistance of K562/A02 to ADM may be involved in enhancement of bcl-2 gene expression of K562/A02 cells co-cultured with MSC, but not in relation to mdr1 gene in K562/A02 cells themselves.

A new method for the fast discrimination of varieties of transgene wheat by means of near infrared spectroscopy and biomimetic pattern recognition (BPR) was proposed and the recognition models of seven varieties of transgene wheat and two varieties of acceptor wheat were built. The experiment adopted 225 samples, which were acquired from nine varieties of wheat. Firstly, a field spectroradiometer was used for collecting spectra in the wave number range from 4 000 to 12 000 cm(-1). Secondly, the original spectral data were pretreated in order to eliminate noise and improve the efficiency of models. Thirdly, principal component analysis (PCA) was used to compress spectral data into several variables, and the cumulate reliabilities of the first ten components were more than 97.28%. Finally, the recognition models were established based on BPR For the every 25 samples in each variety, 15 samples were randomly selected as the training set. The remaining 10 samples of the same variety were used as the first testing set, and all the 200 samples of the other varieties were used as the second testing set. As the 96.7% samples in the second set were correctly rejected, the average correct recognition rate of first testing set was 94.3%. The experimental results demonstrated that the recognition models were effective and efficient. In short, it is feasible to discriminate varieties of transgene wheat based on near infrared spectroscopy and BPR.