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BACKGROUND AND AIMS: Hydrogen sulfide (H 2 S) plays a protective role in NAFLD. However, whether cystathionine γ lyase (CSE), a dominant H 2 S generating enzyme in hepatocytes, has a role in the pathogenesis of NAFLD is currently unclear. APPROACH AND RESULTS: We showed that CSE protein expression is dramatically downregulated, especially in fibrotic areas, in livers from patients with NAFLD. In high-fat diet (HFD)-induced NAFLD mice or an oleic acid-induced hepatocyte model, the CSE/H 2 S pathway is also downregulated. To illustrate a regulatory role for CSE in NAFLD, we generated a hepatocyte-specific CSE knockout mouse (CSE LKO ). Feeding an HFD to CSE LKO mice, they showed more hepatic lipid deposition with increased activity of the fatty acid de novo synthesis pathway, increased hepatic insulin resistance, and higher hepatic gluconeogenic ability compared to CSE Loxp control mice. By contrast, H 2 S donor treatment attenuated these phenotypes. Furthermore, the protection conferred by H 2 S was blocked by farnesoid X receptor (FXR) knockdown. Consistently, serum deoxycholic acid and lithocholic acid (FXR antagonists) were increased, and tauro-β-muricholic acid (FXR activation elevated) was reduced in CSE LKO . CSE/H 2 S promoted a post-translation modification (sulfhydration) of FXR at Cys138/141 sites, thereby enhancing its activity to modulate expression of target genes related to lipid and glucose metabolism, inflammation, and fibrosis. Sulfhydration proteomics in patients' livers supported the CSE/H 2 S modulation noted in the CSE LKO mice. CONCLUSIONS: FXR sulfhydration is a post-translational modification affected by hepatic endogenous CSE/H 2 S that may promote FXR activity and attenuate NAFLD. Hepatic CSE deficiency promotes development of nonalcoholic steatohepatitis. The interaction between H 2 S and FXR may be amenable to therapeutic drug treatment in NAFLD.

Ethnopharmacological relevance The species of the genus Cirsium have been used as traditional Chinese medicine for hundreds of years. It is believed that Cirsium has the efficacies of cooling blood and stopping bleeding, dispelling blood stasis, detoxifying and eliminating carbuncle. At present, they are mainly used in treatment of the hemoptysis, hematemesis, hemoptysis, hematuria, traumatic bleeding and Henoch-Schonlein purpura. They are widely used in traditional Chinese medicine. Aim This paper systematically collated the classification, traditional use, pharmacological action, phytochemistry and clinical application of Cirsium plants in the past ten years, intending to provide a critical appraisal of current knowledge for future in-depth study and rational development and utilization of Cirsium plants. Material and methods This paper searched various databases (SciFinder, Science Direct, CNKI, Wiley online library, Spring Link, Web of Science, PubMed, Wanfang Data, Weipu Data), Chinese Pharmacopoeia 2020 Edition, Chinese Flora, Chinese Materia Medica and some local books on ethnopharmacology. Results More than ten species of Cirsium have been used as folk medicine, and modern pharmacological studies have shown that Cirsium has the effects of protecting liver, antioxidation, anti-tumor, anti-inflammation, antibacterial, etc. More than 200 chemical constituents such as flavonoids, triterpenes, sterols, phenylpropanoids have been isolated from Cirsium. Some ingredients show a wide variety of bioactivities including hepatoprotective, anti-inflammatory, antioxidant, anti-tumor and other activities. At present, Cirsium medicinal plants, as traditional Chinese medicine, were mainly used to treat nephritis, Henoch-Schonlein purpura and hemorrhage, although some species used in folk lack of quality control systems. Conclusion Cirsium plants are a safe and effective medicine for cooling blood and hemostasis. Recent studies on pharmacology and phytochemistry also provide solid scientific evidences for the traditional application of this genus. It also shows significant hepatoprotective activity and may be a potential clinical candidate for the treatment of liver disease. However, the qualitative and quantitative analysis, pharmacokinetics-pharmacodynamics and mechanism of action also need in-depth study.

The northern slope of Tazhong uplift is one of the key areas in the Tarim Basin with great exploration potentials. Previous exploration experiences suggest that strike-slip faults distributed therein play an important role in reservoir formation and hydrocarbon accumulation. In this study, based on the interpretations of the 3D seismic data, six strike-slip fault zones cutting through the Cambrian-Middle Devonian units are identified and characterized. On the seismic cross sections, these faults show a complex geometric feature that consists of a lower positive flower structure in the Cambrian-Upper Ordovician and an upper negative flower structure in the Upper Ordovician-Middle Devonian. On the seismic coherence slices, the lower faults show a linear geometry orienting NNE and only developed within the principal displacement zone. The upper faults are NW trending and display right-stepping en-echelon arrangements. By analyzing the change in the reverse separation of the interface and counting the fault growth index, we suggest that the lower and upper faults developed sequentially in different geological times and formed as a result of two-stage evolution. The lower strike-slip faults may have been formed no early than the Late Ordovician. The upper en-echelon normal faults were developed during the Middle Silurian-Middle Devonian due to the reactivation of the lower strike-slip faults. The horizontal displacement determined from the time slices of faults S1, Sn1 and Sn4 are 743 (±150) m, 1545 (±150) m and 1780 (±150) m, respectively. Such a variation indicates that the amount of horizontal strike-slip displacement is likely to have a tendency to decrease from the south to the north, which agrees well with the regional geodynamics that the compressive stress was transmitted from the south to the north when the strike-slip faults developed during Late Ordovician and Middle Devonian.

As a widely used artificial sweetener, saccharin (SAC) has received extensive attention due to its widespread detection in aquatic environment and potential risk to human health. In this study, the SAC removal by UV-activated persulfate (PS) was comprehensively examined. The results demonstrated that SAC could be eliminated effectively through UV/PS oxidation and its removal behavior can be well described by pseudo-first-order kinetic model. The introduction of different scavengers manifested that sulfate radicals (SO4−∙) were identified to be the major reactive radicals under acidic and neutral conditions, while hydroxyl radicals (HO∙) were determined to be the dominant species under alkaline environments. The reaction rates of SAC with SO4−∙ and HO∙ were calculated to be 1.48 × 108 and 1.56 × 109 M−1 s−1, respectively. The degradation rate constant was positively related to PS dosage (0.21–2.52 mM). The degradation decelerated with the increase of pH from 4.0 to 8.0 and slightly accelerated at pH 9.0. The introduction of Cl− posed a positive impact, while the presence of HCO3−, Br− and humic acid overall retarded SAC removal. Low concentrations of NO3− promoted the degradation, whereas the high levels of NO3− exerted a negative effect. The SAC degradation by UV/PS was mainly initiated through the hydroxylation of the benzene ring, cleavage of C-N bonds, decarboxylation and denitrogenation. The SAC removal in real water matrices by UV/PS treatment was still relatively efficient. Of note, the increased yield of trichloromethane, dichloroacetic acid, trichloroacetic acid and dichloroacetonitrile was found due to chlorination after UV/PS pretreatment.

The curved Tumuxiuke thrust is the northeastern boundary of the Bachu uplift in the Tarim Basin. Based on the interpretation of 2D seismic reflection sections, thick-skinned deformation along the Tumuxiuke structural belt is characterized by monoclinal fault-propagation folds that alternate with push-up structures. The localization and patterns of thick-skinned deformation were controlled by pre-existing normal faults. The forward trishear modeling process further revealed the existence of short-cut thrusts branched from pre-existing normal faults and tested their effect on folding deformation. Monoclines decapitated by low-angle short-cut thrusts coexist with anticlines decapitated by high-angle inverted faults due to the selective inversion of pre-existing normal fault segments. Furthermore, the fault propagation to fault slip ratio (P/S) and the combined effect of multiple propagating thrusts determine the variations in the fold amplification rate and the growth-stratal architecture. The coeval activity of the western Kunlun orogen and the Tumuxiuke thrust in the Cenozoic indicates the far-field transmission of orogenic stress into the distal foreland. Under the approximately N–S-directed compressive stress, inverted structures in nearly W-E-striking segments exhibit monoclinal fault-propagation folds controlled by forethrusts; for the oblique NW-SE-striking segments, the transpressional deformation was partitioned into the frontal contractional deformation zone and the backlimb strike-slip zone.

In this study, apatite fission track (AFT) analyses from opposite sides of the Jianglisai fault are used to constrain the timing of fault activity. Samples collected on the hanging wall have AFT ages between 10 ± 1 and 15 ± 2 Ma and a mean track length ranging from 13.1 ± 0.2 to 13.5 ± 0.2 μm. Samples collected on the footwall have AFT ages between 7.4 ± 0.6 and 9.0 ± 0.9 Ma and a relatively short mean track length that ranges from 11.3 ± 0.2 to 11.6 ± 0.2 μm. AFT modeling revealed that each side experienced two rapid cooling events that were related to tectonic stresses and deformation propagating in a northwestern direction. Combined with electron spin resonance dating constraints, we interpret the rapid cooling of the hanging wall during the Middle Miocene (17–14 Ma) as having recorded that the Jianglisai fault has been active at or prior to ~17 Ma. Both sides of the fault recorded the exhumation event that occurred at approximately 8 Ma, which is responsible for developing the fold-and-thrust belt along the mountain front. The Early Pliocene (about 5 Ma) cooling event indicated that the thrusting-related exhumation in the Jianglisai fault system was a continuously gradual intensified process. The North Altyn Tagh fault system was formed through stepwise thrusting from southeast to northwest during the Middle Miocene to Early Pliocene (17–5 Ma). Since then, the rigid Tarim plate provided constraint on the northward propagation, which likely caused the change from compressional thrusting to thrusting with a left-lateral strike-slip component of the North Altyn Tagh fault system.

This article aims to analyze the main controlling factors of development, distribution and evolution of the fault systems in the Tarim Basin. Based on the seismic profile interpretation, comprehensive analysis of the drilling and geologic data, six fault systems maybe recognized in the Tarim Basin, they are the foreland fault system of the South Tianshan Mountain, the northern Tarim uplift fault system, North Tarim depression fault system, central fault system, Southwest Tarim fault system, and Southeast Tarim fault system. It is indicated that the main differences exist at the development, evolution and distribution of the fault systems in the Tarim Basin. The sub-fault systems can be recognized according to the differences of the fault development and distribution in the interior of the fault system. It is characterized that the multi-level differential development and distribution of the fault systems exist in the Tarim Basin. The fault belt developed in the Paleozoic strata mainly distribute at the paleo-uplift and paleo-slope in the interior of the Tarim Basin, and the fault belt occurred in the Meso-Cenozoic beds mainly develop at the peripheral foreland depressions. Zonal and segment differential development and distribution of the fault systems also exist in the Tarim Basin. The formation and distribution of the Tarim fault systems is of complex controlling mechanisms. Poly-phase structural movement and tectonic transition controls the multi-phase differential development and distribution of the fault systems in the Tarim Basin. Multi-level differential development and distribution is controlled by multi-level detachment belt and regional unconformities. Zonal and segment differential development and distribution of the Tarim fault systems maybe controlled by pre-existed basement structural texture. The major direction of the fault systems in the Tarim Basin is controlled by the later stage basin-mountain coupling.

The Tarim Basin is one of the most important hydrocabon-bearing evaporite basins in China. Four salt-bearing sequences, the Middle and Lower Cambrian, the Mississippian, the Paleogene, and the Neogene, have various thickness and areal distribution. They are important detachment layers and intensely affect the structural deformation in the basin. The Kuqa depression is a subordinate structural unit with abundant salt structures in the Tarim Basin. Salt overthrusts, salt pillows, salt anticlines, salt diapirs, and salt-withdrawal basins are predominant in the depression. Contraction that resulted from orogeny played a key function on the formation of salt structures. Growth strata reveal that intense salt structural deformation in the Kuqa depression occurred during the Himalayan movement from Oligocene to Holocene, with early structural deformation in the north and late deformation in the south. Growth sequences also record at least two phases of salt tectonism. In the Yingmaili, Tahe, and Tazhong areas, low-amplitude salt pillows are the most common salt structures, and these structures are commonly accompanied by thrust faults. The faulting and uplifting of basement blocks controlled the location of salt structures. The differences in the geometries of salt structures in different regions show that the thickness of the salt sequences has an important influence on the development of salt-cored detachment folds and related thrust faults in the Tarim Basin. Salt sequences and salt structures in the Tarim Basin are closely linked to hydrocarbon accumulations. Oil and gas fields have been discovered in the subsalt, intrasalt, and suprasalt strata. Salt deformation has created numerous potential traps, and salt sequences have provided a good seal for the preservation of hydrocarbon accumulations. Large- and small-scale faults related with salt structures have also given favorable migration pathways for oil and gas. When interpreting seismic profiles, special attention needs to be paid to the clastic and carbonate interbeds within the salt sequences because they may lead to incorrect structural interpretation. In the Tarim Basin, the subsalt anticlinal traps are good targets for hydrocarbon exploration.

MAb1, a human IgG1 monoclonal antibody produced in a NS0 cell line, exhibits charge heterogeneity because of the presence of variants formed by processes such as N-terminal glutamate cyclization, C-terminal lysine truncation, deamidation, aspartate isomerization and sialylation in the carbohydrate moiety. Four major charge variants of MAb1 were isolated and the conformations of these charge variants were studied using hydrogen/deuterium exchange mass spectrometry, including the H/D exchange time course (HX-MS) and the stability of unpurified proteins from rates of H/D exchange (SUPREX) techniques. HX-MS was used to evaluate the conformation and solution dynamics of MAb1 charge variants by measuring their deuterium buildup over time at the peptide level. The SUPREX technique evaluated the unfolding profile and relative stability of the charge variants by measuring the exchange properties of globally protected amide protons in the presence of a chemical denaturant. The H/D exchange profiles from both techniques were compared among the four charge variants of MAb1. The two techniques together offered extensive understanding about the local and subglobal/global unfolding of the charge variants of MAb1. Our results demonstrated that all four charge variants of MAb1 were not significantly different in conformation, solution dynamics and chemical denaturant-induced unfolding profile and stability, which aids in understanding the biofunctions of the molecules. The analytical strategy used for conformational characterization may also be applicable to comparability studies done for antibody therapeutics.

We present the results of a seismic wide-angle reflection/refraction profile across the central Qaidam basin, the largest basin within the Qinghai-Tibetan plateau. The 350-km‐long profile extends from the northern margin of the East-Kunlun Shan to the southern margin of the Qilian Shan. The P- and S-wave velocity structure and Poisson's ratio data provide constraints on composition. The crust here consists of a near-surface sedimentary layer and a four-layered crystalline crust having several significant features. (1) The sedimentary fill of the Qaidam basin reaches a maximum thickness of 8 km, and the basin shape mirrors the uplifted Moho. (2) Within the four layers of the crystalline crust, P- (S-) wave velocities increase with depth and fall within the following velocity ranges: 5.9–6.3 km/s (3.45–3.65 km/s), 6.45–6.55 km/s (3.7 km/s), 6.65 km/s (3.8 km/s), and 6.7–6.9 km/s (3.8–3.9 km/s), respectively; (3) low-velocity zones with a 3–5% reduction in seismic velocity are detected in the lower half of the crust beneath the Qaidam basin and its transition to the Qilian Shan. (4) The crystalline crust is thickest beneath the northern margin of the basin towards the Qilian Shan (58–62 km) and thinnest beneath the center of the basin (52 km). Variations in crustal thickness are caused most pronouncedly by thickness variations in the lowermost layer of the crust. (5) Poisson's ratio and P-wave velocity values suggest that the Qaidam crust has an essentially felsic composition with an intermediate layer at its base. Based on the crustal structure reported here, we suggest that late Cenozoic convergence is accommodated by thick-skinned tectonic deformation with thickening involving the entire crust across the Kunlun–Qaidam–Qilian system.

A three-dimensional (3D) structural modeling of the Lower Cambrian–Upper Permian Yubei 3D area was performed to understand its structural evolution. This model reproduces the present-day structure of the basin and comprises 11 horizons within Lower Cambrian to Upper Permian rocks. The analysis is based on 3D depth views and faults. The results image salt movements due to tectonics and/or burial. From these observations, this paper deduces that salt structures are correlated to the main faults and tectonic events. From the model analysis, we interpret the timing and geometry of Tarim Basin tectonics. The fault geometry can be resolved based on the strike of the fault, the morphology of hanging wall strata, and the stratigraphic distribution. Emphasis is placed on gypsum rock detachment, considering its movements during the Middle Caledonian event and decoupling effects during tectonic evolution. Moreover, we point to the structural control of the Paleozoic basement and the crustal architecture (Yubei 3D Zone) on the geometry of the Tarim Basin.

Hydrocarbon preservation conditions have restricted exploration in the Middle and Upper Yangtze, and structural deformation and fluid activity have played an important role in the origin and preservation of oil and gas. In order to study that how the deformation and fluid activity impact the hydrocarbon preservation, we did some field work and collected some calcite vein samples for analysis of deformation periods using acoustic emission and fluid inclusions. Combined with previous studies, the strata distribution, tectonic deformation and fluid characteristics show that there are three structural belts in the study area: East Sichuan, West Hunan and Hubei and the northwestern periphery of the Xuefeng Uplift, and that their tectonic deformation style, fluid inclusion characteristics and hydrocarbon preservation are different. The breakthrough thrusts were well developed in the anticline core, and a lot of hydrocarbon inclusions were found in calcite veins around the thrusts in East Sichuan. The breakthrough thrusts were only in the syncline core in West Hunan and Hubei, and the brine inclusions did not contain hydrocarbon in calcite veins around the thrusts. Many breakthrough thrusts were found in the northwestern periphery of the Xuefeng Uplift, where there were only rare calcite veins. The deformation and hydrocarbon inclusion indicated that when there was no fault breakthrough in East Sichuan, the Paleozoic covered by the Triassic regional cap was good for hydrocarbon preservation. The strata above the Lower Paleozoic were denuded, and lots of brine inclusions and deep infiltration of surface water were found in the West Hunan and Hubei, so only the part of the syncline area with a well developed Silurian regional cap had good preservation conditions. Intense tectonic movements and denudation were widely developed in the northwestern periphery of the Xuefeng Uplift, where there were only paleo-reservoirs, non-hydrocarbon fluid activity and poor preservation conditions.

The salt beds of the Middle-Lower Cambrian are widespread in the middle-west parts of the Central Uplift and adjacent areas, the Tarim Basin. This paper presents the results of seismic interpretation and drilling data analysis, which discovered that the salt beds were formed in an old geologic age, deeply buried, with relatively small scaled flowing and gathering and uneven distribution. As the regional detachment layers, the salt sequences considerably control the structural deformation of the up-salt Paleozoic, forming a series of hydrocarbon traps. In due course, the salt beds of the Middle-Lower Cambrian provide excellent cap rocks and trap conditions; thus the value of exploring hydrocabon reservoir in the target strata of the sub-salt Sinian-Cambrian is greatly increased. Research has shown that the salt-related structures of the Middle-Lower Cambrian in the area mainly exist in the form of salt pillow, salt roller, up-salt anticline, salt diapir, assemblage of the salt arch and up-salt fault-block, assemblage of basement fault and salt anticline, assemblage of the basement fault-block and salt dome, assemblage of salt detachment and fault-related fold, and assemblage of basement fault-block, salt arch and up-salt imbricated thrusts. The evolution and deformation mechanisms of the salt-related structures are controlled largely by basement faulting, compressional shortening, plastic flowing and gathering, superstratum gravitation, and up-salt faulting and detaching. They are distributed in rows or belts along basement faults or fault block belts.

Many complex structures have developed in the Longmen Mountains thrust belt, SW China, over the course of polyphase tectonic movements in the region. Based on field investigations and interpretations of seismic sections, we divided the belt into the following three segments and two transfer zones (from northeast to southwest): the northern segment, Anxian transfer zone (Ta), central segment, Guanxian transfer zone (Tg), and southern segment. The northern segment, located north of Anxian County, consists of the Jiaoziding nappe, comprising a Triassic–Jurassic fold belt and a plastically deformed Silurian belt. The northern segment can be further divided into four sub-segments: the Guangyuan–Chaotianyi sub-segment (N1), Baitianba–Guangyuan sub-segment (N2), Wenxingchang–Baitianba sub-segment (N3), and Wuzhong Mountain–Tangwangzhai nappe sub-segment (N4). The Anxian transfer zone (Ta), located between Yuanmenba Town and Hanwangchang Town, consists of numerous thrust faults and strike-slip faults at shallow levels, with duplexes and detachment structures at deeper levels. The central segment, which consists of the Jiudingshan nappe and numerous klippes and thrust faults, is located between Hanwangchang Town and Guanxian County. This segment can be divided into two sub-segments: the Mianzhu–Mianyang sub-segment (C1) and the Dayuanbao sub-segment (C2). The Guanxian transfer zone, which is characterized by numerous thrust faults, strike-slip faults, and duplexes, is located between Guanxian County and Huaiyuan County. The southern segment, which consists of the Baoxing nappe and contains arcuate thrust faults, is located south of Huaiyuan County. The southern segment is divided into three sub-segments: the Huaiyuan–Xinchang sub-segment (S1), Xinchang–Lushan sub-segment (S2), and southern arcuate sub-segment (S3).

Polygonal faults, generally distributed in fine-grained sediments, are layer-bound faults and are important in hydrocarbon accumulation. Using 3D seismic data, we analyzed the plane and profile features of faults developed in the Qingshankou formation of the Sanzhao sag. We identified these faults as having typical features of polygonal faults: 1) layer-bound; 2) normal faults; 3) slight fault displacements and steep in dip angles; 4) multi-directional in strike and 5) a single fault has a short horizontal extension. In addition, these faults intersect each other and form polygons. These polygonal faults are the result from the combined action of compaction, volume contraction and episodic hydraulic fracturing, conditions favorable for oil/gas accumulation. They are the dominant channels for migration of fluids in the Qingshankou mudstone, forming a large number of fault-lithologic oil traps. Polygonal faults improve reservoirs.

Through field geological investigation and seismic interpretation of the Longmen (龙门) Mountain thrust belt, we summarized the following structural styles: thrust belt, fault-related fold (fault bend fold, fault propagation fold, and fault decollement fold), pop-up, triangle zone, duplex, superimposed fold, ductile deformation structures, reverse thrust fault, klippe, decollement structure, etc.. These structural styles have evident distribution characteristics; they had zonation and segmentation in plane. The zonation presents as the thrust nappe tectonic zone to the west of Tongjichang (通济场) fault, fault-related folds between Tongjichang fault and Guankou (关口) fault, and low and mild folds to the east of Guankou fault. The segmentation is evidenced as the scale of reverse thrust faults was minor between Tongjichang No. 1 fault and Tongjichang No. 2 fault. The distance between these two faults became long in the Dayuanbao (大园包) structure, and there developed typical fault propagation fold and pop-up between these two faults. Furthermore, the structures had stratification in profile. The salt layer of T2l provided good conditions for the formation and development of large listric thrust faults; the thrust fault slipped in the salt layer and formed decollement structures and fault-related fold. At the same time, there formed duplex and reverse thrust faults between the two decollement layers.

Wrench motion is relatively common in basins but often goes undetected because of its subtle structural imprint. Even so wrench-related folding is of significance in petroleum exploration and development. Based on the Riedel shear nomenclature, we apply the model of wrench-related folding to deformation in the Bohai sea basin. The folding related to R-shears, T-tensional structural systems (T-systems) and C-compressive structural systems (C-systems) in a Riedel shear model are discussed. The R-system related folding results from differential movements between the two sides of fault blocks, in map view the fold is oriented (90°-φ/2) (in the initial deformation stage) or more than (90°-φ/2) from the principle displacement zone (PDZ), where φ is the angle of internal friction. The T-system related folding is related to the rollover of the hanging wall, and in map view the fold is initiated at 45° from the PDZ in the initial deformation stage. The C-system related folding is resulted from the compression induced by a wrench action, in map view the fold was oriented 45° from initial deformation in the PDZ. Bohai Sea basin fold orientations fit our models, and the wrench-related folds play important roles in oil and gas accumulation.

The Longmen Mountains thrust belt contains complex structures resulting from multi-phase tectonic movements. Field investigations and interpretations of seismic profiles reveal two important transfer zones in the thrust belt: the Anxian and Guanxian transfer zones. Many thrust and strike-slip faults are found in the shallow part of the transfer zones, and duplexes and detachment structures in the deep part. The Anxian transfer zone is located between the Jiaoziding and Jiudingshan nappes, consisting mainly of the Lower Triassic Feixianguan Formation (T1f) and Jianglingjiang Formation (T1j), and Middle Triassic Leikoupo Formation (T2l). The Guanxian transfer zone is located between the Baoxing and Jiudingshan nappes, consisting mainly of Devonian, Carboniferous, Triassic, Jurassic, and Presinian rocks. This zone contains many thrust faults, strike-slip faults, and duplexes in its deeper part (where early structures have been almost completely overprinted), and many klippens are found at the surface.

By analyzing the balanced cross sections and subsidence history of the Longmen Mountain thrust belt, China, we concluded that it had experienced five tectonic stages: (1) the formation stage (T3x) of the miniature of Longmen Mountain, early Indosinian movement, and Anxian tectonic movement created the Longmen Mountain; (2) the stable tectonic stage (J1) where weaker tectonic movement resulted in the Longmen Mountain thrust belt being slightly uplifted and slightly subsiding the foreland basin; (3) the intense tectonic stage (J2.3), namely the early Yanshan movement; (4) continuous tectonic movement (K-E), namely the late Yanshan movement and early Himalayan movement; and (5) the formation of Longmen Mountain (N-Q), namely the late Himalayan movement. During those tectonic deformation stages, the Anxian movement and Himalayan movement played important roles in the Longmen Mountain's formation. The Himalayan movement affected Longmen Mountain the most; the strata thrust intensively and were eroded severely. There are some klippes in the middle part of the Longmen Mountain thrust belt because a few nappes were pushed southeastward in later tectonic deformation.

Field investigation and seismic section explanation showed that the Longmen Mountain Thrust Belt has obvious differential deformation: zonation, segmentation and stratification. Zonation means that, from NW to NE, the Longmen Mountain Thrust Belt can be divided into the Songpan-Garze Tectonic Belt, ductile deformation belt, base involved thrust belt, frontal fold-thrust belt, and foreland depression. Segmentation means that it can be divided into five segments from north to south: the northern segment, the Anxian Transfer Zone, the center segment, the Guanxian Transfer Zone and the southern segment. Stratification means that the detachment layers partition the structural styles in profile. The detachment layers in the Longmen Mountain Thrust Belt can be classified into three categories: the deep-level detachment layers, including the crust-mantle system detachment layer, intracrustal detachment layer, and Presinian system basal detachment layer; the middle-level detachment layers, including Cambrian-Ordovician detachment layer, Silurian detachment layer, etc.; and shallow-level detachment layers, including Upper Triassic Xujiahe Formation detachment layer and the Jurassic detachment layers. The multi-level detachment layers have a very important effect on the shaping and evolution of Longmen Mountain Thrust Belt.

Attention has been paid to the deformations in the south and north foreland basins of the Tianshan Mountains and their relations to the tectonic movements of the mountains. Based on the seismic data interpretation and field work, the tectonic features, tectonic styles, controlling factors of deformation, deformation time, and their relationships in the three tectonic units were comparably studied. The Cenozoic deformations in the two foreland basins were characterized by zonation from south to north, segmentation from west to east, and layering from deep to shallow. The tectonic styles are compressive ones, including both basement-involved and cover-detaching. The two foreland basins underwent several times of deformation in Cenozoic and the deformations were transmitted from the Tianshan orogen to the inner basin. The deformation dynamics of the south and north foreland basins of the Tianshan Mountains can be represented by dynamics of orogenic wedges. In terms of the deformations of the wedges with wave-like features, the concept of a wave orogenic wedge was put forward, and a double wave orogenic wedge model was established.

As is well known that many decollement layers were developed in the Longmenshan thrust belt, Sichuan Basin, China. Through field investigation, explanation of seismic profiles and analysis of the balanced sections, we can divide the decollement zones into 3 categories: (1) the deep level decollement zones, including the crust-mantle decollement layer, intracrustal decollement layer, and presinian basal decollement layer. The main structural styles of their deformation are the crust-mantle decoupling detachment deformation, the basal ductile shear deformation, etc.; (2) the middle level decollement zones, including the Cambrian-Ordovician decollement layer, the Silurian decollement layer, etc., the main structural styles of their deformation are the isopachous fold, the angular fold, the saddle structure, and the combination styles of them; and (3) the shallow level decollement zones, including the Xujiahe Formation decollement layer of Upper Triassic and the Jurassic decollement layers, the main structural styles of their deformation are the thrust-nappe tectonic, the pop-up, the triangle zone, the duplex, etc. Multi-level decollement zones not only made the Longmenshan thrust belt develop many different deformation styles from deep place to shallow place, but also made some local areas have the superimposition of the tectonic deformation apparently. This study indicates that the multi-level decollement zones have a very important effect on the shaping and evolution of the Longmenshan thrust belt.

Combined evidence from the outcrop and the fluid inclusion assemblage (FIA) analysis indicates that there exist two episodes of fluid flow controlled by the tectonic activity. The first episode was recorded mainly in the reservoir rock of the Honghuayuan Formation, representing the fluid flow of hydrocarbon charging. The second episode occurred mainly along the fault systems, representing the fluid movement when the ancient oil reservoir was destroyed. The host mineral morphology, homogeneous temperature, and salinity of the FIAs record an episodic fluid movement. Characters of high homogenous temperature, low salinity and a quick temperature variation of the first episode fluid flow may indicate an early-stage fluid eruption, and correspondingly, fine-grained calcite was formed. Temperature of the erupted fluid tended to decrease during its mixing with the upper formation fluid and finally had the same temperature as the upper formation. From then on, the temperature was rather steady and favored the growth of the coarse calcite. Due to this character of the temperature variation of the episodic fluid flow, we can use the homogenous temperature of the FIA of the coarse calcite to date the formation and the destruction time of the Majiang ancient oil reservoir. Episodic fluid flow was known for its inhomogeneous trapping, which resulted in the failure of dating according to the burial history. But taking a close look at its temperature variation, we think that the latest stage of fluid flow, characterized by steady state temperature and grow of the coarser crystals, can be used for dating. It will be of great value if this method is proved to be effective. The formation and the destruction time of the Majiang ancient oil reservoir were dated to be in the Indosinian Period and the late Yanshan-early Hymalayan Period respectively. This conclusion is in great discrepancy with the common accepted idea that the Majiang ancient oil reservoir was formed and destroyed during the Caledonian tectonic movement. Even so, this paper further discussed its reliability from the view of the source rock evolution and also the local tectonic evolution.

Northeast Sichuan basin is a Mesozoic-Cenozoic basin in the northern margin of the Yangtze plate which has a complex tectonic background and hydrocarbon accumulation history. By means of the analysis method of wave processes, major cycles of sedimentary wave process in this basin have been studied. The results show that there are five-order cycles corresponding to 760, 220, 100, 35 and 20 Ma respectively, two first-order sedimentary cycles (220 Ma) and four secondorder sedimentary cycles (100 Ma). The authors find that the second-order sedimentary cycles are well matched with reservoir formation cycles through studying the relationship between second-order sedimentary cycles and reservoir formation cycles, and divide three reservoir formation cycles in this basin.

The salt beds of Lower Tertiary developed in the mid-segment of Kuqa foreland fold belt, northern Tarim basin. They considerably controlled structural deformation of the belt. According to the field observation, seismic profile interpretation and drilling data, three different structural styles of supra-salt, intra-salt and sub-salt occurred in the Kuqa foreland fold belt. Supra-salt structural styles mainly include thrust faults and fault-related sags. Intra-slat structural styles essentially are salt-pillows, intra-salt faults and folds, and salt weld structures. Sub-salt structural styles mainly consist of imbricated thrust faults, duplex structures, pop-up and fault-related folds. It is indicated that great differences exist among supra-salt, intra-salt and sub-salt structures of Kuqa foreland fold belt. The salt-related structures were formed in the same structural stress field. The dynamic mechanism of the salt-related structures is mainly associated with gravitation, compression and plastic flow of salt beds.

The Kuqa foreland between the Tarim basin and the Tianshan Mountains is rich in oil and gas. Based on field work and seismic profiles, the structural styles and their formation mechanisms were determined, and the role of evaporites in the deformation was demonstrated. The main structural styles in the overburden are detachment folds, large scale nappes, triangle zones, gentle and wide synclines, fault-propagation folds and pop-ups. The main structures in the substrate are small-scale thrust faults, duplexes, pop-ups and fault-bend and fault-propagation folds, and formed mainly at the end of the Pliocene under north-south compression. The evaporite layer in the lower section of the Paleogene is the decollement zone for the disharmonic deformations in the overburden and in the substrate. The detachment along the evaporite layer made it possible for compressive stresses to be transmitted farther in the overburden than in the substrate. Deformation in the overburden is more extensive than in the substrate at the leading edge of deformation. At the trailing edge of deformation, the structural highs in the overburden closely correspond to those in the substrate, which is of significance for petroleum exploration in the western Kuqa foreland.

Thick salt beds in the Lower Tertiary were developed in the Kuqa foreland fold belt of the northern Tarim Basin. The salt beds controlled the structural deformation and hydrocarbon accumulation of the belts. Because of the salt beds, the Meso-Cenozoic structures of the Kuqa foreland fold belts can be divided into three major tectono-sequences: suprasalt structures, salt bed structures and subsalt structures. Suprasalt structures include thrusts and fault-related folds. Salt bed structures are dominated by salt pillows, allochthonous salt sheets, salt welds and fish-tail structures. Subsalt structures mainly include imbricated thrust belts, duplex structures, fault-related folds and pop-up structures. Formation of the salt structures in the Kuqa foreland fold belts is controlled by compression, gravitational gliding and gravitational spreading. The basin-mountain coupling and compression resulted in intense shortening of the fold belt. The rising of the South Tianshan Mountains caused the gravity gliding and gravity spreading. Plastic flow deformation of the salt beds resulted in salt thickening from the mountain front to the south of the fold belt. The thick salt bed accumulated in the Klasu and Qiulitag structural belts, and controlled the distribution of the salt-related structural traps and oil–gas pools. The structural traps have a bearing upon salt beds in the Kuqa foreland fold belts. The source rocks are mainly located below the salt beds, which can act as excellent cap rocks and seal the gas pools. The subsalt beds are the favorable places for hydrocarbons to accumulate.

This paper mainly replies to the discussion by Li et al (2009) on the calculation of the detachment depths in the Kuqa Depression. We think that viscous material flowing into or out of the cross section can affect the validity of the calculation method, yet the number of detachment levels does not bring any drawbacks to the calculation. In the Kuqa Depression, the salt flow influenced the structural deformation to some extent, and affected slightly the accuracy of the calculated depths of the true detachment levels. However, it does not mean that the calculation method loses effectiveness in the study area. Therefore, the calculation results are still relatively believable.

REVP-TE is the signaling protocol of GMPLS, which is widely applied in ASON. When it is used to set up a connection, the distribution of messages usually adopts the serial or the parallel mode as well as several new proposed methods. Considering the drawbacks in both of the methods, and the lack of a fast message sending method suitable for inter-domain optical network, we propose a novel inter-domain signaling protocol MDSP based on the topology aggregation of inter-domain and new added new message types for RSVP-TE. MDSP introduces a mixed message distribution methodserial distribution in intra-domain and parallel distribution in inter-domain. Through mathematical analysis and network simulation, it's proved to be an efficient signaling protocol, achieving a less connection setup time and blocking probability in multi-domain.

An asparagine-to-serine substitution at residue 370 (N370S) in glucocerebrosidase (GCase) is the most prevalent mutation leading to Gaucher's disease, the most common lysosomal storage disorder. Two types of hydrogen/deuterium exchange experiment coupled with proteolysis and liquid chromatography-mass spectrometry (HDX-MS) were used to investigate the dynamic properties and unfolding stability of wt, R495H, and N370S GCases in the presence and absence of ligands. R495H GCase is used for enzyme replacement therapy and is considered to be a wt surrogate, whereas N370S is the most prevalent mutation leading to Gaucher's disease. Time-course HDX experiments of the GCases were performed under near-physiological conditions to detect the protein's local unfolding motions at a submolecular level. In guanidine-titration experiments, HDX reactions were performed with various concentrations of a chemical denaturant to provide the global stability of the proteins. The two types of experiment showed that all three purified GCases, wt, R495H, and N370S, have virtually identical local unfolding motions and global stabilities in solution. Combined with previous X-ray crystallographic studies, which showed indistinguishable backbone conformations for N370S and R495H GCase mutants and very similar melting temperatures for the wt, R495H, and N370S mutants, all three GCases are likely to have virtually identical structural and dynamic properties in solution. The guanidine-titration experiments revealed that the pharmacological chaperone, isofagomine (IFG), interacts more weakly with the N370S mutant than with the R495H GCase; this is consistent with the higher IC(50) value of IFG against N370S than against R495H. The time-course experiments showed that IFG restricts the local unfolding motions of N370S in the same way as those of R495H when the ligand saturates the proteins.

Molecular chaperones are a highly diverse group of proteins that recognize and bind unfolded proteins to facilitate protein folding and prevent nonspecific protein aggregation. The mechanisms by which chaperones bind their protein substrates have been studied for decades. However, there are few reports about the affinity of molecular chaperones for their unfolded protein substrates. Thus, little is known about the relative binding affinities of different chaperones and about the relative binding affinities of chaperones for different unfolded protein substrates. Here we describe the application of SUPREX (stability of unpurified proteins from rates of H-D exchange), an H-D exchange and MALDI-based technique, in studying the binding interaction between the molecular chaperone Hsp33 and four different unfolded protein substrates, including citrate synthase, lactate dehydrogenase, malate dehydrogenase, and aldolase. The results of our studies suggest that the cooperativity of the Hsp33 folding-unfolding reaction increases upon binding with denatured protein substrates. This is consistent with the burial of significant hydrophobic surface area in Hsp33 when it interacts with its substrate proteins. The SUPREX-derived K(d) values for Hsp33 complexes with four different substrates were all found to be within the range of 3-300 nM.

Described here is a new technique, termed SPROX (stability of proteins from rates of oxidation), that can be used to measure the thermodynamic stability of proteins and protein-ligand complexes. SPROX utilizes hydrogen peroxide in the presence of increasing concentrations of a chemical denaturant to oxidize proteins. The extent of oxidation at a given oxidation time is determined as a function of the denaturant concentration using either electrospray or matrix-assisted laser desorption/ionization mass spectrometry. Ultimately, the denaturant concentration dependence of the oxidation reaction rate is used to evaluate a folding free energy (DeltaG(f)) and m value (deltaDeltaG(f)/delta[Den]) for the protein's folding/unfolding reaction. Measurements of such SPROX-derived DeltaG(f) and m values on proteins in the presence and absence of ligands can also be used to evaluate protein-ligand affinities (e.g., DeltaDeltaG(f) and Kd values). Presented here are SPROX results obtained on four model protein systems including ubiquitin, ribonuclease A (RNaseA), cyclophilin A (CypA), and bovine carbonic anhydrase II (BCAII). SPROX-derived DeltaG(f) and m values on these proteins are compared to values obtained using more established techniques (e.g., CD spectroscopy and SUPREX). The dissociation constants of several known protein-ligand complexes involving these proteins were also determined using SPROX and compared to previously reported values. The complexes included the CypA-cyclosporin A complex and the BCAII-4-carboxybenzenesulfonamide complex. The accuracy and precision of SPROX-derived thermodynamic parameters for the model proteins and protein-ligand complexes in this study are discussed as well as the caveats of the technique.

Publisher Summary This chapter discusses the applications of the “stability of unpurified proteins from rates of hydrogen/deuterium exchange” (SUPREX) technique to the thermodynamic analysis of protein folding and ligand binding. The requisite experimental protocols for SUPREX data acquisition and analysis are briefly described. SUPREX is a useful tool for measuring the protein folding free energies, binding free energies, and binding affinities. SUPREX is distinguished from other hydrogen/deuterium (H/D) exchange- and mass-spectrometry-based approaches for the analysis of protein stability and ligand binding in its use of chemical denaturant. Unique experimental advantages of SUPREX over existing methods for making the same types of thermodynamic measurements include the technique's high-throughput capabilities and the capacity for studying multicomponent mixtures. These advantages make SUPREX a promising technique that could open the door to the study of proteins under conditions that more closely resemble the conditions inside a cell—for example, the technique could be used to study protein folding under the conditions of molecular crowding or in the presence of molecular chaperones. There is also the possibility of examining the thermodynamic properties of large multiprotein complexes by SUPREX.

A protocol was developed to characterize the domain-specific thermodynamic stabilities of multidomain proteins using SUPREX (Stability of Unpurified Proteins from Rates of H/D Exchange). The protocol incorporates a protease digestion step into the conventional SUPREX protocol and enables folding free energy (DeltaGf) and cooperativity (m-value) measurements to be made on the individual domains of multidomain proteins in their native context (i.e., in the intact protein). Three multidomain protein systems (calmodulin, a Fyn construct, and transferrin) were used to validate the SUPREX-protease digestion protocol. The DeltaGf and m-value of each domain in the intact test proteins were measured in the absence and presence of ligands using the new protocol. Domain-specific thermodynamic parameters were obtained on each system; and the measured parameters were consistent with known biophysical properties of the test proteins. The known stabilization of the N-terminal domain of CaM in the context of the intact protein and the known binding affinity of a proline-rich peptide to the SH3 domain in the Fyn construct were successfully quantified using the new protocol. Qualitative information about the relative calcium binding affinities of the N- and C-terminal domains of CaM and about the relative iron binding affinities of the N- and C-terminal domains of transferrin was also obtained using the new protocol.

The equilibrium unfolding properties of four model protein systems were characterized using SUPREX (stability of unpurified proteins from rates of H/D exchange). SUPREX is an H/D exchange- and mass spectrometry-based technique for measuring the free energy (DeltaGf) and m-value (deltaDeltaGf/delta[denaturant]) associated with the folding/unfolding reaction of a protein. The model proteins in this study (calmodulin, carbonic anhydrase II, RmlB, Bcl-xL) were chosen to test the applicability of SUPREX to the thermodynamic analysis of larger (approximately 15 kDa) or multidomain proteins. In the absence of ligand, DeltaGf and m-values for these proteins could not be evaluated using the conventional data acquisition and analysis methods previously established for SUPREX. However, ligand-bound forms of the proteins were amenable to conventional SUPREX analyses, and it was possible to evaluate reasonably accurate and precise binding free energies of selected ligands. In some cases, protein-ligand dissociation constants (Kd values) could also be ascertained. The SUPREX-derived binding free energies and Kd values evaluated here were in good agreement with those reported on the same complexes using other techniques.