Purpose: This study focused on maintaining and improving the walking function of late-stage older individuals while longitudinally tracking the effects of regular exercise programs in a day-care service specialized fo...Purpose: This study focused on maintaining and improving the walking function of late-stage older individuals while longitudinally tracking the effects of regular exercise programs in a day-care service specialized for preventive care over 5 years, using detailed gait function measurements with an accelerometer-based system. Methods: Seventy individuals (17 male and 53 female) of a daycare service in Tokyo participated in a weekly exercise program, meeting 1 - 2 times. The average age of the participants at the start of the program was 81.4 years. Gait function, including gait speed, stride length, root mean square (RMS) of acceleration, gait cycle time and its standard deviation, and left-right difference in stance time, was evaluated every 6 months. Results: Gait speed and stride length improved considerably within six months of starting the exercise program, confirming an initial improvement in gait function. This suggests that regular exercise programs can maintain or improve gait function even age groups that predictably have a gradual decline in gait ability due to enhanced age. In the long term, many indicators tended to approach baseline values. However, the exercise program seemingly counteracts age-related changes in gait function and maintains a certain level of function. Conclusions: While a decline in gait ability with aging is inevitable, establishing appropriate exercise habits in late-stage older individuals may contribute to long-term maintenance of gait function.展开更多
Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. M...Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. Methods: Thirty-two late-stage elderly individuals were evaluated for knee pain during rest, walking, and program exercises, with and without TENS. Gait analysis was performed using an IoT-based gait analysis device to examine the effects of TENS-induced analgesia on gait. Results: TENS significantly reduced knee pain during rest, walking, and programmed exercises, with the greatest analgesic effect observed during walking. The greater the knee pain without TENS, the more significant the analgesic effect of TENS. A comparison of gait parameters revealed a significant difference only in the gait cycle time, with a trend towards faster walking with TENS;however, the effect was limited. Conclusion: TENS effectively relieves knee pain in late-stage elderly individuals and can be safely applied during exercise. Pain management using TENS provides important insights into the implementation of exercise therapy in this age group.展开更多
Complex superimposed basins exhibit multi-stage tectonic events and multi-stage reservoir formation; hydrocarbon reservoirs formed in the early stage have generally late-stage genesis characteristics after undergoing ...Complex superimposed basins exhibit multi-stage tectonic events and multi-stage reservoir formation; hydrocarbon reservoirs formed in the early stage have generally late-stage genesis characteristics after undergoing adjustment, reconstruction and destruction of later-stage multiple tectonic events. In this paper, this phenomenon is called the late-stage reservoir formation effect. The late-stage reservoir formation effect is a basic feature of oil and gas-forming reservoirs in complex superimposed basins, revealing not only multi-stage character, relevance and complexity of oil and gas- forming reservoirs in superimposed basins but also the importance of late-stage reservoir formation. Late-stage reservoir formation is not a basic feature of oil and gas forming reservoir in superimposed basins. Multi-stage reservoir formation only characterizes one aspect of oil and gas-forming reservoir in superimposed basins and does not represent fully the complexity of oil and gas-forming reservoir in superimposed basins. We suggest using ＂late-stage reservoir formation effect＂ to replace the ＂late-stage reservoir formation＂ concept to guide the exploration of complex reservoirs in superimposed basins. Under current geologic conditions, the late-stage reservoir formation effect is represented mainly by four basic forms： phase transformation, scale reconstruction, component variation and trap adjustment. The late-stage reservoir formation effect is produced by two kinds of geologic processes： first, the oil and gas retention function of various geologic thresholds （hydrocarbon expulsion threshold, hydrocarbon migration threshold, and hydrocarbon accumulating threshold） causes the actual time of oil and gas reservoir formation to be later than the time of generation of large amounts of hydrocarbon in a conventional sense, producing the late-stage reservoir formation effect; second, multiple types of tectonic events （continuously strong reconstruction, early-stage strong reconstruction, middle-stage strong reconstruction, late-stage strong reconstruction and long-term stable sedimentation） after oil and gas reservoir formation lead to adjustment, reconstruction and destruction of reservoirs formed earlier, and form new secondary hydrocarbon reservoirs due to the late-stage reservoir formation effect.展开更多
Neotectonism occurred intensively in the Bozhong depression in the Bohai Bay Basin, which was reflected vertically by dramatic subsidence and a number of uplifts and laterally by notable fault movements. This particul...Neotectonism occurred intensively in the Bozhong depression in the Bohai Bay Basin, which was reflected vertically by dramatic subsidence and a number of uplifts and laterally by notable fault movements. This particularity has resulted in the special petroleum geological conditions of the Bozhong depression which are different from those of adjacent lands. For example, the source rocks of the Shahejie Formation were overpressured and hydrocarbon generation occurred in the late stage; the Dongying Formation was deeply buried below the hydrocarbon-generating threshold, therefore there were sufficient oil sources. The rapid subsidence led to starved sedimentation of the Guantao Formation fine sandstone and the regional Minghuazhen Formation lacustrine shale, which formed the Neogene regional reservoir-caprock association. The active faults formed in the neotectonism became passages for oil to migrate from the Paleogene to Neogene. The traps formed by late fault activity and accompanied anticlines provided spaces for the formation of reservoirs. All the above factors match well with one another in the Bozhong depression, providing favorable conditions for the formation of a series of large oilfields in the region展开更多
Oceanic plateaus are large igneous provinces in the oceans,created by massive underwater eruptions,but their late-stage volcanism is poorly understood.With the addition of recent high-quality bathymetric data to exist...Oceanic plateaus are large igneous provinces in the oceans,created by massive underwater eruptions,but their late-stage volcanism is poorly understood.With the addition of recent high-quality bathymetric data to existing data,286 secondary cones were discovered over Shatsky Rise oceanic plateau.These cones with steeper flank slopes(mean 6.1°±4.4°)and smaller sizes(102–1923 m in height)are morphologically distinct from the plateau,and they are thought to have formed after the main volcanic episodes.Cone height and characteristic height(420 m)are close to seamounts in the Pacific Ocean,whereas greater than those in the Atlantic Ocean.Mean flatness of Shatsky Rise’s cones(0.25±0.20)are similar to that of seamounts in both Pacific and Atlantic Oceans,but notably density in cone distribution(0.56 km^-3)and their mean slope are significantly lower than those of seamounts in the two oceans.Lower slopes of secondary cones within Shatsky Rise may be explained by higher effusion rates of remaining magma.Although cone formation was expected to have a link to rifting by seafloor spreading,weak relationship between cone orientation and magnetic anomaly pattern implies that the expectation is negative.Moreover,weak correlation between the cone height and depth indicates it is not true that volcanic cones grow taller when they occur closer to the massif summits with thicker oceanic crust,which was suggested as the increase in hydraulic pressure.Cone height and flatness are also not strongly related,implying that remaining magma supply was too limited to foster the cones to critical height.展开更多
New structural and petrological data unveil a very complicated ductile deformation history of the Xiongdian-Suhe HP metamorphic unit, north-western Dabie Shan, central China. The fine-grained symplectic amphibolite-fa...New structural and petrological data unveil a very complicated ductile deformation history of the Xiongdian-Suhe HP metamorphic unit, north-western Dabie Shan, central China. The fine-grained symplectic amphibolite-facies assemblage and coronal structure enveloping eclogite-facies garnet, omphacite and phengite etc., representing strain-free decompression and retrogressive metamorphism, are considered as the main criteria to distinguish between the early-stage deformation under HP metamorphic conditions related to the continental deep subduction and collision, and the late-stage deformation under amphibolite to greenschist-facies conditions occurred in the post-eclogite exhumation processes. Two late-stages of widely developed, sequential ductile deformations D 3 and D 4, are recognized on the basis of penetrative fabrics and mineral aggregates in the Xiongdian-Suhe HP metamorphic unit, which shows clear, regionally, consistent overprinting relationships. D 3 fabrics are best preserved in the Suhe tract of low post-D 3 deformation intensity and characterized by steeply dipping layered mylonitic amphibolites associated with doubly vergent folds. They are attributed to a phase of tectonism linked to the initial exhumation of the HP rocks and involved crustal shortening with the development of upright structures and the widespread emplacement of garnet-bearing granites and felsic dikes. D 4 structures are attributed to the main episode of ductile extension (D 1 4) with a gently dipping foliation to the north and common intrafolial, recumbent folds in the Xiongdian tract, followed by normal sense top-to-the north ductile shearing (D 2 4) along an important tectonic boundary, the so-called Majiawa-Hexiwan fault (MHF), the westward continuation of the Balifan-Mozitan-Xiaotian fault (BMXF) of the northern Dabie Shan. It is indicated that the two stages of ductile deformation observed in the Xiongdian-Suhe HP metamorphic unit, reflecting the post-eclogite compressional or extrusion wedge formation, the subhorizontal ductile extension and crustal thinning as well as the top-to-the north shearing along the high-angle ductile shear zones responsible for exhumation of the HP unit as a coherent slab, are consistent with those recognized in the Dabie-Sulu UHP and HP metamorphic belts, suggesting that they were closely associated in time and space. The Xiongdian-Suhe HP metamorphic unit thus forms part of the Triassic (250-230 Ma) collision orogenic belt, and can not connect with the South Altun-North Qaidam-North Qinling UHP metamorphic belt formed during the Early Paleozoic (500-400 Ma).展开更多
Objective Two important geological issues have long been controversial in the Xing-Meng area of North China. The first concerns the final closure of Paleo-Asian Ocean in Xing-Meng area, and the other concerns the fol...Objective Two important geological issues have long been controversial in the Xing-Meng area of North China. The first concerns the final closure of Paleo-Asian Ocean in Xing-Meng area, and the other concerns the folding and lifting of the Xing-Meng Trough. The focus of thses issues is the Late Permian sedimentary environment, which is generally considered to be either an exclusively continental environment or from the closed inland sea environment in the Early to Middle stage to continental lacustrine environment in the late stage. In recent years, we have successively discovered abundant typical marine fossils （e.g., bryozoans and calcareous algae） in the Upper Permian thick limestone layer from Linxi County and Ar Horqin Banner in eastern region of Inner Mongolia and Jiutain County in Jilin Province. These significant findings have attracted the attention from fellow academics.展开更多
Late stage colorectal carcinoma is very complicated in its molecular mechanisms. One hundred andnine cases of colorectal carcinomas were analyzed with RFLP method for the allelic deletion of chromosome 17short arms (A...Late stage colorectal carcinoma is very complicated in its molecular mechanisms. One hundred andnine cases of colorectal carcinomas were analyzed with RFLP method for the allelic deletion of chromosome 17short arms (ADCC17p) In this study. The results showed that frs(luency of allelic deletion of chromosome 17short arms (FADC17P) in Dukes’ D stage (95 % ) was higher than those in Dukes’ A, B. C stages (54% 68% ); Fisher’s exact test P <0. 01; FADC17p in colorectal carcinomas with distant metastasis (95 % ) washigher than those without distant metastasis, Fisher’s exact test P <0. 01 However, there were no significant differences in FADC 1 7p between the colorectal carcinomas with lymph node metastasis and those without lymph node metastasis (P >0. 05). Therefore, it is considered that ADC17p is an important diagnosticmarker of late stage colorectal carcinomas, and indicates a poor prognosis.展开更多
Synthetic chemistry plays an indispensable role in drug discovery,contributing to hit compounds identification,lead compounds optimization,candidate drugs preparation,and so on.As Nobel Prize laureate James Black emph...Synthetic chemistry plays an indispensable role in drug discovery,contributing to hit compounds identification,lead compounds optimization,candidate drugs preparation,and so on.As Nobel Prize laureate James Black emphasized,“the most fruitful basis for the discovery of a new drug is to start with an old drug”1.Late-stage modification or functionalization of drugs,natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse elements into bioactive compounds promptly.Such modifications alter the chemical space and physiochemical properties of these compounds,ultimately influencing their potency and druggability.To enrich a toolbox of chemical modification methods for drug discovery,this review focuses on the incorporation of halogen,oxygen,and nitrogen—the ubiquitous elements in pharmacophore components of the marketed drugs—through late-stage modification in recent two decades,and discusses the state and challenges faced in these fields.We also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functionalized molecules.Ultimately,we hope this review would serve as a valuable resource,facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.展开更多
Late-stage is defined here as the period when Neotectonism occurred since 5.1 Ma. Most petroliferous basins in China lie in the areas where Neotectonism occurred intensively. In recent years, Chinese petroleum geologi...Late-stage is defined here as the period when Neotectonism occurred since 5.1 Ma. Most petroliferous basins in China lie in the areas where Neotectonism occurred intensively. In recent years, Chinese petroleum geologists have paid much attention to late-stage petroleum accumulation. The PL19-3 giant oilfield is situated where faulting activities occurred violently during Neotectonism. To understand the mechanism of lat-stage rapid accumulation, we discussed the most important aspects responsible for the formation of the giant oilfield, including oil generation, active oil-source rock occurrence, fault activity and fault conduits, late-stage rapid oil injection as well as the distinguishing indicators. This study shows that: (1) sufficient oil was supplied to the PL19-3 field since 5.1 Ma because the PL19-3 structure was surrounded by four sags in which three intervals of high-quality source rocks remained active during Neotectonism; (2) densely distributed faults and high porosity/permeability sandstone carrier beds comprised the effective conduit system for oil migration and injection; (3) oil migrated along the faults and charged the PL19-3 structure rapidly by means of seismic pumping which was triggered by frequent earthquakes during Neotetonism. It is documented that elevated reservoir temperature, abnormal geothermal gradients and abnormally high homogenization temperatures of the fluid inclusions are the indicators for late-stage rapid oil accumulation.展开更多
The palladium-catalyzed late-stage aroylation of 4-methyl-1,5-diaryl-lH-pyrazole-3-carboxylates has been developed via direct and exclusive mono-Csp^2-H bond activation with broad substrate scope and good functional g...The palladium-catalyzed late-stage aroylation of 4-methyl-1,5-diaryl-lH-pyrazole-3-carboxylates has been developed via direct and exclusive mono-Csp^2-H bond activation with broad substrate scope and good functional group tolerance. A dual-core dimeric palladacycle is confirmed by X-ray single crystal crystallography, and probably serves as an active species in the catalytic cycle.展开更多
A unified protecting group-free approach to two stemarene and two betaerene diterpenoids through a bioinspired two-phase strategy has been developed,and three of them were obtained for the first time via chemical synt...A unified protecting group-free approach to two stemarene and two betaerene diterpenoids through a bioinspired two-phase strategy has been developed,and three of them were obtained for the first time via chemical synthesis.Starting from a common intermediate,two distinct tetracyclic frameworks containing diastereoisomeric bridged bicycles were constructed by a divergent ring reorganization strategy.Late-stage C–H functionalization through a xanthylation-oxygenation protocol furnished the corresponding oxygenated stereocenters or oxo functionality in high regio-and diastereoselective fashion within a complex hydrocarbon system.The stereochemical puzzles in(–)-2-acetoxybetaer13(17)-ene and(+)-7-acetoxybetaer-13(17)-ene were first predicted by the comparison of density functional theory(DFT)-nuclear magnetic resonance(NMR)data with the reported data and then unambiguously addressed through the total syntheses of natural products and three diastereomers.展开更多
C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds’bioactivity.Significant advances in this field have been achieved in the past few years,mainly,t...C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds’bioactivity.Significant advances in this field have been achieved in the past few years,mainly,the C–H functionalization system in(hetero)aryl C–H activation owing to the importance of(hetero)aryl moiety in pharmaceutical.In this review,we described the selected recent examples of how developed intermolecular C(sp^(2))–H functionalization methodologies involving diverse techniques diversify pharmaceutical molecules in the late stage.展开更多
The installation of azoles via C–H/N–H cross-coupling is significantly underdeveloped,particularly in benzylic C–H azolation due to the requirement for external chemical oxidants and the challenge in controlling th...The installation of azoles via C–H/N–H cross-coupling is significantly underdeveloped,particularly in benzylic C–H azolation due to the requirement for external chemical oxidants and the challenge in controlling the site-and chemo-selectivity.Herein,a late-stage azolation of benzylic C‒H bonds enabled by electrooxidation is described,which proceeds in an undivided cell under mild,catalyst-and chemical-oxidant-free reaction conditions.The strategy empowers the C‒H azolation on primary,secondary,and even challenging tertiary benzylic positions selectively.The remarkable synthetic utility of our approach is highlighted by its easy scalability without overoxidation of products and ample scope with valuable functional groups.The approach can be directly used to install benzyl and azole motifs on highly functionalized drug molecules.展开更多
Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with en...Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with enhanced biological activities or improved therapeutic capabilities compared to their natural counterparts. Recent years, transition-metal-promoted functionalization of ubiquitous C-H bonds has been emerged as a powerful and tunable tool in this area, both for backbone diversifications and labeling of specific moieties. These reactions were flexible and expedient in both academic and industrial laboratories, especially considering their atom and step-economy, good functional group compatibility, accurate site selectivity. This review surveys the progress achieved in the late-stage modification of peptides and proteins utilizing transition-metal-catalyzed C-H functionalization with C-C and C-X(F, Cl, O, N, B, etc.) bonds formation.展开更多
Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-pro...Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.展开更多
A ruthenium-catalyzed electrochemical dehydrogenative C(sp^(2))H acyloxylation of aniline derivatives with carboxylic acids has been developed.Electric current is used to recycle the active ruthenium-based catalyst an...A ruthenium-catalyzed electrochemical dehydrogenative C(sp^(2))H acyloxylation of aniline derivatives with carboxylic acids has been developed.Electric current is used to recycle the active ruthenium-based catalyst and promote H_(2) evolution.This method significantly expands the scope and enhances the selectivity of metal-electron catalyzed mono-and di-acyloxylations,which remain challenged.Our findings allowed mono-selectivity in broadly effective late-stage diversification of structurally complex drugs and natural product molecules,tolerating drugs,natural products and amino acids.The method and its underlying strategy are expected to have widespread uses in functional aniline synthesis and drug discovery process.展开更多
文摘Purpose: This study focused on maintaining and improving the walking function of late-stage older individuals while longitudinally tracking the effects of regular exercise programs in a day-care service specialized for preventive care over 5 years, using detailed gait function measurements with an accelerometer-based system. Methods: Seventy individuals (17 male and 53 female) of a daycare service in Tokyo participated in a weekly exercise program, meeting 1 - 2 times. The average age of the participants at the start of the program was 81.4 years. Gait function, including gait speed, stride length, root mean square (RMS) of acceleration, gait cycle time and its standard deviation, and left-right difference in stance time, was evaluated every 6 months. Results: Gait speed and stride length improved considerably within six months of starting the exercise program, confirming an initial improvement in gait function. This suggests that regular exercise programs can maintain or improve gait function even age groups that predictably have a gradual decline in gait ability due to enhanced age. In the long term, many indicators tended to approach baseline values. However, the exercise program seemingly counteracts age-related changes in gait function and maintains a certain level of function. Conclusions: While a decline in gait ability with aging is inevitable, establishing appropriate exercise habits in late-stage older individuals may contribute to long-term maintenance of gait function.
文摘Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. Methods: Thirty-two late-stage elderly individuals were evaluated for knee pain during rest, walking, and program exercises, with and without TENS. Gait analysis was performed using an IoT-based gait analysis device to examine the effects of TENS-induced analgesia on gait. Results: TENS significantly reduced knee pain during rest, walking, and programmed exercises, with the greatest analgesic effect observed during walking. The greater the knee pain without TENS, the more significant the analgesic effect of TENS. A comparison of gait parameters revealed a significant difference only in the gait cycle time, with a trend towards faster walking with TENS;however, the effect was limited. Conclusion: TENS effectively relieves knee pain in late-stage elderly individuals and can be safely applied during exercise. Pain management using TENS provides important insights into the implementation of exercise therapy in this age group.
基金State Key Basic Research "973" Program (2006CB202308) for funding this research
文摘Complex superimposed basins exhibit multi-stage tectonic events and multi-stage reservoir formation; hydrocarbon reservoirs formed in the early stage have generally late-stage genesis characteristics after undergoing adjustment, reconstruction and destruction of later-stage multiple tectonic events. In this paper, this phenomenon is called the late-stage reservoir formation effect. The late-stage reservoir formation effect is a basic feature of oil and gas-forming reservoirs in complex superimposed basins, revealing not only multi-stage character, relevance and complexity of oil and gas- forming reservoirs in superimposed basins but also the importance of late-stage reservoir formation. Late-stage reservoir formation is not a basic feature of oil and gas forming reservoir in superimposed basins. Multi-stage reservoir formation only characterizes one aspect of oil and gas-forming reservoir in superimposed basins and does not represent fully the complexity of oil and gas-forming reservoir in superimposed basins. We suggest using ＂late-stage reservoir formation effect＂ to replace the ＂late-stage reservoir formation＂ concept to guide the exploration of complex reservoirs in superimposed basins. Under current geologic conditions, the late-stage reservoir formation effect is represented mainly by four basic forms： phase transformation, scale reconstruction, component variation and trap adjustment. The late-stage reservoir formation effect is produced by two kinds of geologic processes： first, the oil and gas retention function of various geologic thresholds （hydrocarbon expulsion threshold, hydrocarbon migration threshold, and hydrocarbon accumulating threshold） causes the actual time of oil and gas reservoir formation to be later than the time of generation of large amounts of hydrocarbon in a conventional sense, producing the late-stage reservoir formation effect; second, multiple types of tectonic events （continuously strong reconstruction, early-stage strong reconstruction, middle-stage strong reconstruction, late-stage strong reconstruction and long-term stable sedimentation） after oil and gas reservoir formation lead to adjustment, reconstruction and destruction of reservoirs formed earlier, and form new secondary hydrocarbon reservoirs due to the late-stage reservoir formation effect.
基金This project is supported by the NationM Natural Science Foundation of China(No.40238059).
文摘Neotectonism occurred intensively in the Bozhong depression in the Bohai Bay Basin, which was reflected vertically by dramatic subsidence and a number of uplifts and laterally by notable fault movements. This particularity has resulted in the special petroleum geological conditions of the Bozhong depression which are different from those of adjacent lands. For example, the source rocks of the Shahejie Formation were overpressured and hydrocarbon generation occurred in the late stage; the Dongying Formation was deeply buried below the hydrocarbon-generating threshold, therefore there were sufficient oil sources. The rapid subsidence led to starved sedimentation of the Guantao Formation fine sandstone and the regional Minghuazhen Formation lacustrine shale, which formed the Neogene regional reservoir-caprock association. The active faults formed in the neotectonism became passages for oil to migrate from the Paleogene to Neogene. The traps formed by late fault activity and accompanied anticlines provided spaces for the formation of reservoirs. All the above factors match well with one another in the Bozhong depression, providing favorable conditions for the formation of a series of large oilfields in the region
基金supported by the National Key R&D Program of China (No. 2018YFC0309800)the National Natural Science Foundation of China (Nos. 91628301, U1606401, 41606069, 41776058)+2 种基金the Natural Science Foundation of Guangdong Province in China (No. 2017A030313243)the Chinese Academy of Sciences (Nos. Y4SL021001, QYZDY-SSWDQC005)the China Association of Marine Affairs (No. CAMAZD201714)
文摘Oceanic plateaus are large igneous provinces in the oceans,created by massive underwater eruptions,but their late-stage volcanism is poorly understood.With the addition of recent high-quality bathymetric data to existing data,286 secondary cones were discovered over Shatsky Rise oceanic plateau.These cones with steeper flank slopes(mean 6.1°±4.4°)and smaller sizes(102–1923 m in height)are morphologically distinct from the plateau,and they are thought to have formed after the main volcanic episodes.Cone height and characteristic height(420 m)are close to seamounts in the Pacific Ocean,whereas greater than those in the Atlantic Ocean.Mean flatness of Shatsky Rise’s cones(0.25±0.20)are similar to that of seamounts in both Pacific and Atlantic Oceans,but notably density in cone distribution(0.56 km^-3)and their mean slope are significantly lower than those of seamounts in the two oceans.Lower slopes of secondary cones within Shatsky Rise may be explained by higher effusion rates of remaining magma.Although cone formation was expected to have a link to rifting by seafloor spreading,weak relationship between cone orientation and magnetic anomaly pattern implies that the expectation is negative.Moreover,weak correlation between the cone height and depth indicates it is not true that volcanic cones grow taller when they occur closer to the massif summits with thicker oceanic crust,which was suggested as the increase in hydraulic pressure.Cone height and flatness are also not strongly related,implying that remaining magma supply was too limited to foster the cones to critical height.
文摘New structural and petrological data unveil a very complicated ductile deformation history of the Xiongdian-Suhe HP metamorphic unit, north-western Dabie Shan, central China. The fine-grained symplectic amphibolite-facies assemblage and coronal structure enveloping eclogite-facies garnet, omphacite and phengite etc., representing strain-free decompression and retrogressive metamorphism, are considered as the main criteria to distinguish between the early-stage deformation under HP metamorphic conditions related to the continental deep subduction and collision, and the late-stage deformation under amphibolite to greenschist-facies conditions occurred in the post-eclogite exhumation processes. Two late-stages of widely developed, sequential ductile deformations D 3 and D 4, are recognized on the basis of penetrative fabrics and mineral aggregates in the Xiongdian-Suhe HP metamorphic unit, which shows clear, regionally, consistent overprinting relationships. D 3 fabrics are best preserved in the Suhe tract of low post-D 3 deformation intensity and characterized by steeply dipping layered mylonitic amphibolites associated with doubly vergent folds. They are attributed to a phase of tectonism linked to the initial exhumation of the HP rocks and involved crustal shortening with the development of upright structures and the widespread emplacement of garnet-bearing granites and felsic dikes. D 4 structures are attributed to the main episode of ductile extension (D 1 4) with a gently dipping foliation to the north and common intrafolial, recumbent folds in the Xiongdian tract, followed by normal sense top-to-the north ductile shearing (D 2 4) along an important tectonic boundary, the so-called Majiawa-Hexiwan fault (MHF), the westward continuation of the Balifan-Mozitan-Xiaotian fault (BMXF) of the northern Dabie Shan. It is indicated that the two stages of ductile deformation observed in the Xiongdian-Suhe HP metamorphic unit, reflecting the post-eclogite compressional or extrusion wedge formation, the subhorizontal ductile extension and crustal thinning as well as the top-to-the north shearing along the high-angle ductile shear zones responsible for exhumation of the HP unit as a coherent slab, are consistent with those recognized in the Dabie-Sulu UHP and HP metamorphic belts, suggesting that they were closely associated in time and space. The Xiongdian-Suhe HP metamorphic unit thus forms part of the Triassic (250-230 Ma) collision orogenic belt, and can not connect with the South Altun-North Qaidam-North Qinling UHP metamorphic belt formed during the Early Paleozoic (500-400 Ma).
基金financially supported by the National Natural Science Foundation of China (grant No.41572098)the geological survey project (grants No.121201103000161114 and 121201103000150019 ) of the China Geological Survey
文摘Objective Two important geological issues have long been controversial in the Xing-Meng area of North China. The first concerns the final closure of Paleo-Asian Ocean in Xing-Meng area, and the other concerns the folding and lifting of the Xing-Meng Trough. The focus of thses issues is the Late Permian sedimentary environment, which is generally considered to be either an exclusively continental environment or from the closed inland sea environment in the Early to Middle stage to continental lacustrine environment in the late stage. In recent years, we have successively discovered abundant typical marine fossils （e.g., bryozoans and calcareous algae） in the Upper Permian thick limestone layer from Linxi County and Ar Horqin Banner in eastern region of Inner Mongolia and Jiutain County in Jilin Province. These significant findings have attracted the attention from fellow academics.
文摘Late stage colorectal carcinoma is very complicated in its molecular mechanisms. One hundred andnine cases of colorectal carcinomas were analyzed with RFLP method for the allelic deletion of chromosome 17short arms (ADCC17p) In this study. The results showed that frs(luency of allelic deletion of chromosome 17short arms (FADC17P) in Dukes’ D stage (95 % ) was higher than those in Dukes’ A, B. C stages (54% 68% ); Fisher’s exact test P <0. 01; FADC17p in colorectal carcinomas with distant metastasis (95 % ) washigher than those without distant metastasis, Fisher’s exact test P <0. 01 However, there were no significant differences in FADC 1 7p between the colorectal carcinomas with lymph node metastasis and those without lymph node metastasis (P >0. 05). Therefore, it is considered that ADC17p is an important diagnosticmarker of late stage colorectal carcinomas, and indicates a poor prognosis.
基金Financial support from the National Key R&D Program of China(No.2021YFA1501700)the National Natural Science Foundation of China(Nos.22293014,22131002,22161142019,81821004)+1 种基金the Ministry of Science and Technology of China Changping Laboratory,Peking University Special Fund for COVID-19the New Cornerstone Science Foundation through the XPLORER PRIZE。
文摘Synthetic chemistry plays an indispensable role in drug discovery,contributing to hit compounds identification,lead compounds optimization,candidate drugs preparation,and so on.As Nobel Prize laureate James Black emphasized,“the most fruitful basis for the discovery of a new drug is to start with an old drug”1.Late-stage modification or functionalization of drugs,natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse elements into bioactive compounds promptly.Such modifications alter the chemical space and physiochemical properties of these compounds,ultimately influencing their potency and druggability.To enrich a toolbox of chemical modification methods for drug discovery,this review focuses on the incorporation of halogen,oxygen,and nitrogen—the ubiquitous elements in pharmacophore components of the marketed drugs—through late-stage modification in recent two decades,and discusses the state and challenges faced in these fields.We also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functionalized molecules.Ultimately,we hope this review would serve as a valuable resource,facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.
基金supported by Program for Innovative Research Team in the University (Grant No. IRT0658)National Natural Science Foundation of China (Grant No. 90914006)
文摘Late-stage is defined here as the period when Neotectonism occurred since 5.1 Ma. Most petroliferous basins in China lie in the areas where Neotectonism occurred intensively. In recent years, Chinese petroleum geologists have paid much attention to late-stage petroleum accumulation. The PL19-3 giant oilfield is situated where faulting activities occurred violently during Neotectonism. To understand the mechanism of lat-stage rapid accumulation, we discussed the most important aspects responsible for the formation of the giant oilfield, including oil generation, active oil-source rock occurrence, fault activity and fault conduits, late-stage rapid oil injection as well as the distinguishing indicators. This study shows that: (1) sufficient oil was supplied to the PL19-3 field since 5.1 Ma because the PL19-3 structure was surrounded by four sags in which three intervals of high-quality source rocks remained active during Neotectonism; (2) densely distributed faults and high porosity/permeability sandstone carrier beds comprised the effective conduit system for oil migration and injection; (3) oil migrated along the faults and charged the PL19-3 structure rapidly by means of seismic pumping which was triggered by frequent earthquakes during Neotetonism. It is documented that elevated reservoir temperature, abnormal geothermal gradients and abnormally high homogenization temperatures of the fluid inclusions are the indicators for late-stage rapid oil accumulation.
基金the National Natural Science Foundation of China(Nos. 21476074 and 21676088)for financial support
文摘The palladium-catalyzed late-stage aroylation of 4-methyl-1,5-diaryl-lH-pyrazole-3-carboxylates has been developed via direct and exclusive mono-Csp^2-H bond activation with broad substrate scope and good functional group tolerance. A dual-core dimeric palladacycle is confirmed by X-ray single crystal crystallography, and probably serves as an active species in the catalytic cycle.
基金Financial support from the National Natural Science Foundation of China(nos.22071205,21772164,and 21572187)NFFTBS(no.J1310024),and PCSIRT is acknowledged.
文摘A unified protecting group-free approach to two stemarene and two betaerene diterpenoids through a bioinspired two-phase strategy has been developed,and three of them were obtained for the first time via chemical synthesis.Starting from a common intermediate,two distinct tetracyclic frameworks containing diastereoisomeric bridged bicycles were constructed by a divergent ring reorganization strategy.Late-stage C–H functionalization through a xanthylation-oxygenation protocol furnished the corresponding oxygenated stereocenters or oxo functionality in high regio-and diastereoselective fashion within a complex hydrocarbon system.The stereochemical puzzles in(–)-2-acetoxybetaer13(17)-ene and(+)-7-acetoxybetaer-13(17)-ene were first predicted by the comparison of density functional theory(DFT)-nuclear magnetic resonance(NMR)data with the reported data and then unambiguously addressed through the total syntheses of natural products and three diastereomers.
基金the National Natural Science Foundation(Nos.21907071,22271200,and 21801178)the Sichuan Science and Technology Program(No.2020YJ0091)+2 种基金the Post-Doctor Research Project,West China Hospital,Sichuan University(No.2019HXBH008)Natural Science Foundation of Sichuan,China(Nos.2023NSFSC1716,2023NSFSC0645)the China Postdoctoral Science Foundation(No.2018M633360)for financial support.
文摘C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds’bioactivity.Significant advances in this field have been achieved in the past few years,mainly,the C–H functionalization system in(hetero)aryl C–H activation owing to the importance of(hetero)aryl moiety in pharmaceutical.In this review,we described the selected recent examples of how developed intermolecular C(sp^(2))–H functionalization methodologies involving diverse techniques diversify pharmaceutical molecules in the late stage.
基金This work was supported by the National Natural Science Foundation of China(21901052,81872759)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2019)+1 种基金the Guangzhou Education Bureau University Scientific Research Project(201831845)the Guangdong Basic and Applied Basic Research Foundation(2020A1515010722).
文摘The installation of azoles via C–H/N–H cross-coupling is significantly underdeveloped,particularly in benzylic C–H azolation due to the requirement for external chemical oxidants and the challenge in controlling the site-and chemo-selectivity.Herein,a late-stage azolation of benzylic C‒H bonds enabled by electrooxidation is described,which proceeds in an undivided cell under mild,catalyst-and chemical-oxidant-free reaction conditions.The strategy empowers the C‒H azolation on primary,secondary,and even challenging tertiary benzylic positions selectively.The remarkable synthetic utility of our approach is highlighted by its easy scalability without overoxidation of products and ample scope with valuable functional groups.The approach can be directly used to install benzyl and azole motifs on highly functionalized drug molecules.
基金the support from the National Key R&D Program of China(No. 2017YFA0505400)the National Natural Science Foundation of China (Nos. 21572214, 21702200)
文摘Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with enhanced biological activities or improved therapeutic capabilities compared to their natural counterparts. Recent years, transition-metal-promoted functionalization of ubiquitous C-H bonds has been emerged as a powerful and tunable tool in this area, both for backbone diversifications and labeling of specific moieties. These reactions were flexible and expedient in both academic and industrial laboratories, especially considering their atom and step-economy, good functional group compatibility, accurate site selectivity. This review surveys the progress achieved in the late-stage modification of peptides and proteins utilizing transition-metal-catalyzed C-H functionalization with C-C and C-X(F, Cl, O, N, B, etc.) bonds formation.
基金financially supported by the National Natural Science Foundation of China(Nos.21977075,22271200,21801178,21907070,81971653)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,Central Plains Science and Technology Innovation Leader Project(No.214200510008 to L.Li)Scientific and Technological Innovation Team of Colleges and Universities in Henan Province(No.21IRTSTHN001)。
文摘Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.
基金We thank the National Natural Science Foundation of China(Nos.22078298,21978271,21706234 and 21676253)the Natural Science Foundation of Zhejiang Province of China(No.LY19B060011)for financial support.
文摘A ruthenium-catalyzed electrochemical dehydrogenative C(sp^(2))H acyloxylation of aniline derivatives with carboxylic acids has been developed.Electric current is used to recycle the active ruthenium-based catalyst and promote H_(2) evolution.This method significantly expands the scope and enhances the selectivity of metal-electron catalyzed mono-and di-acyloxylations,which remain challenged.Our findings allowed mono-selectivity in broadly effective late-stage diversification of structurally complex drugs and natural product molecules,tolerating drugs,natural products and amino acids.The method and its underlying strategy are expected to have widespread uses in functional aniline synthesis and drug discovery process.
