Earthquake supercycles and fault interaction over the past 32 ka in the Lake Ebinur area, Xinjiang, China.

Earthquake prediction and disaster assessment in tectonically active regions require a continuous and complete regional seismic archive, which is commonly difficult to obtain, especially for prehistoric records. Here, high-resolution analysis of the sedimentary sequence from Lake Ebinur in Xinjiang revealed a detailed history of environment evolution since 32 ka ago. Both the Cl content and ultrafine proportion revealed the changing climate: the climate was relatively dry with low lake-water volumes from 32 to 12 ka, while the climate became warmer and wetter since 12 ka. In addition, eight earthquakes were identified by comprehensive analysis of grain size and geochemical element proxies, showing more than two seismic supercycles, with gaps of ∼10.4 ka; these gaps are much larger than those inferred previously (∼4-7 ka). Notably, these seismic events exhibited a pattern of mutual transmittance between the BoA and Jinghenan faults. Such fault interaction can occur in the Lake Ebinur area because it is dominated by weak lithosphere in which strain is easily accumulated and released; the interaction can also be attributed to the unique spatial distribution and immature nature of both faults. Combined with trenching investigations, our high-resolution analysis of lacustrine sediments can reveal a complete history of tectonic activity, which can efficiently serve regional earthquake prediction and disaster assessment.

Diversity in fatty acid elongation enzymes: The FabB long-chain ß-ketoacyl-ACP synthase I initiates fatty acid synthesis in Pseudomonas putida F1.

The condensation of acetyl-CoA with malonyl-acyl carrier protein (ACP) by ß-ketoacyl-ACP synthase III (KAS III, FabH) and decarboxylation of malonyl-ACP by malonyl-ACP decarboxylase are the two pathways that initiate bacterial fatty acid synthesis (FAS) in Escherichia coli. In addition to these two routes, we report that Pseudomonas putida F1 ß-ketoacyl-ACP synthase I (FabB), in addition to playing a key role in fatty acid elongation, also initiates FAS in vivo. We report that although two P. putida F1 fabH genes (PpfabH1 and PpfabH2) both encode functional KAS III enzymes, neither is essential for growth. PpFabH1 is a canonical KAS III similar to E. coli FabH whereas PpFabH2 catalyzes condensation of malonyl-ACP with short- and medium-chain length acyl-CoAs. Since these two KAS III enzymes are not essential for FAS in P. putida F1, we sought the P. putida initiation enzyme and unexpectedly found that it was FabB, the elongation enzyme of the oxygen-independent unsaturated fatty acid pathway. P. putida FabB decarboxylates malonyl-ACP and condenses the acetyl-ACP product with malonyl-ACP for initiation of FAS. These data show that P. putida FabB, unlike the paradigm E. coli FabB, can catalyze the initiation reaction in FAS.

An atypical 3-ketoacyl ACP synthase III required for acyl homoserine lactone synthesis in Pseudomonas syringae pv. syringae B728a.

The last step of the initiation phase of fatty acid biosynthesis in most bacteria is catalyzed by the 3-ketoacyl-acyl carrier protein (ACP) synthase III (FabH). Pseudomonas syringae pv. syringae strain B728a encodes two FabH homologs, Psyr_3467 and Psyr_3830, which we designated PssFabH1 and PssFabH2, respectively. Here, we explored the roles of these two 3-ketoacyl-ACP synthase (KAS) III proteins. We found that PssFabH1 is similar to the Escherichia coli FabH in using acetyl-acetyl-coenzyme A (CoA ) as a substrate in vitro, whereas PssFabH2 uses acyl-CoAs (C4-C10) or acyl-ACPs (C6-C10). Mutant analysis showed that neither KAS III protein is essential for the de novo fatty acid synthesis and cell growth. Loss of PssFabH1 reduced the production of an acyl homoserine lactone (AHL) quorum-sensing signal, and this production was partially restored by overexpressing FabH homologs from other bacteria. AHL production was also restored by inhibiting fatty acid elongation and providing exogenous butyric acid. Deletion of PssFabH1 supports the redirection of acyl-ACP toward biosurfactant synthesis, which in turn enhances swarming motility. Our study revealed that PssFabH1 is an atypical KAS III protein that represents a new KAS III clade that functions in providing a critical fatty acid precursor, butyryl-ACP, for AHL synthesis.IMPORTANCEAcyl homoserine lactones (AHLs) are important quorum-sensing compounds in Gram-negative bacteria. Although their formation requires acylated acyl carrier proteins (ACPs), how the acylated intermediate is shunted from cellular fatty acid synthesis to AHL synthesis is not known. Here, we provide in vivo evidence that Pseudomonas syringae strain B728a uses the enzyme PssFabH1 to provide the critical fatty acid precursor butyryl-ACP for AHL synthesis. Loss of PssFabH1 reduces the diversion of butyryl-ACP to AHL, enabling the accumulation of acyl-ACP for synthesis of biosurfactants that contribute to bacterial swarming motility. We report that PssFabH1 and PssFabH2 each encode a 3-ketoacyl-acyl carrier protein synthase (KAS) III in P. syringae B728a. Whereas PssFabH2 is able to function in redirecting intermediates from ß-oxidation to fatty acid synthesis, PssFabH1 is an atypical KAS III protein that represents a new KAS III clade based on its sequence, non-involvement in cell growth, and novel role in AHL synthesis.

E/e' Ratio and Diastolic Function Between Deep Vein Catheterization and Internal Fistula Treatment in Patients with Chronic Kidney Disease.

Objective: To examine the relationship between diastolic function and the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity (E/e') in patients with chronic renal disease who had deep vein catheterization and internal fistula. Methods: The clinical data of 50 uremia patients treated at The Affiliated Dongyang Hospital of Wenzhou Medical University from January 2020 to January 2022 were retrospectively analyzed. To assess the differences in E/e' ratio and patients' diastolic function between the two groups, they were split into two teams according to the various therapy modalities: the internal fistula team (n = 42) and the deep vein catheterization team (n = 8). Results: After treatment, the left ventricular end-diastolic diameter (LVd), E peak, a peak and E/A value, the volume and area of four chambers of the left ventricle (LV), the volume and area of two chambers of LV in both groups were significantly lower than those before treatment (P < .001). After treatment, the LVd left ventricular end-systolic diameter (LVs), the four-chamber volume of LV, and the two-chamber volume and area of LV in patients with internal fistula were significantly lower than those in patients with deep vein catheterization (P < .001). After treatment, E peak, A peak and E/A value, e' interventricular septum, E/e' value of interventricular septum, e' lateral wall, and E of lateral wall in patients with internal fistula group. Conclusion: Both deep vein catheterization and internal fistula treatment can improve the diastolic function and reduce the pulmonary pressure of uremic patients to a certain extent, but internal fistula treatment is better than deep vein catheterization in reducing LVd, LVs, LV four-chamber volume, LV two-chamber volume and area, and the effects of both in improving the E/e ratio of patients are not obvious.

Novel mandelic acid derivatives suppress virulence of Ralstonia solanacearum via type III secretion system.

BACKGROUND: Bacterial wilt induced by Ralstonia solanacearum is regarded as one of the most devastating diseases. However, excessive and repeated use of the same bactericides has resulted in development of bacterial resistance. Targeting bacterial virulence factors, such as type III secretion system (T3SS), without inhibiting bacterial growth is a possible assay to discover new antimicrobial agents. RESULTS: In this work, identifying new T3SS inhibitors, a series of mandelic acid derivatives with 2-mercapto-1,3,4-thiazole moiety was synthesized. One of them, F-24, inhibited the transcription of hrpY gene significantly. The presence of this compound obviously attenuated hypersensitive response (HR) without inhibiting bacterial growth of R. solanacearum. The transcription levels of those typical T3SS genes were reduced to various degrees. The test of the ability of F-24 in protecting plants demonstrated that F-24 protected tomato plants against bacterial wilt without restricting the multiplication of R. solanacearum. The mechanism of this T3SS inhibition is through the PhcR-PhcA-PrhG-HrpB pathway. CONCULSION: The screened F-24 could inhibit R. solanacearum T3SS and showed better inhibitory activity than previously reported inhibitors without affecting the growth of the strain, and F-24 is a compound with good potential in the control of R. solanacearum. © 2023 Society of Chemical Industry.

CuCo Nanoparticle, Pd(II), and l-Proline Trifunctionalized UiO-67 Catalyst for Three-Step Sequential Asymmetric Reactions.

Metal-organic frameworks (MOFs) have become a promising support for different active sites to construct multifunctional and heterogeneous catalysts. However, the related investigation mainly focuses on introducing one or two active sites into MOFs and trifunctional catalysts have been very rarely reported. Herein, non-noble CuCo alloy nanoparticles, Pd2+, and l-proline, as encapsulated active species, functional organic linkers, and active metal nodes, respectively, were successfully decorated to UiO-67 to construct a chiral trifunctional catalyst by the one-step method, which was further applied to asymmetric three-step sequential oxidation of aromatic alcohols/Suzuki coupling/asymmetric aldol reactions with excellent oxidation and coupling performance (yields up to 95 and 96%, respectively), as well as good enantioselectivities (eeanti value up to 73%) in asymmetric aldol reactions. The heterogeneous catalyst can be reused at least five times without obvious deactivation due to the strong interaction between the MOFs and the active sites. This work provides an effective strategy to construct multifunctional catalysts via the introduction and combination of three or more of active sites, including encapsulated active species, functional organic linkers, and active metal nodes, into stable MOFs.

Strongest chemical weathering in response to the coldest period in Guyuan, Ningxia, China, during 14-11 Ma.

Moisture evolution in Central Asia including Northwest China shows less similarity with its surroundings and attracts a growing number of studies. In this study, a well-dated thick lacustrine sequence is chosen in Northwest China and detailed geochemical analysis is conducted during the Middle Miocene Climate Transition (MMCT, 14-11 Ma). The multi-proxy records (Na2O/Al2O3, CIA, Rb/Sr) revealed that chemical weathering was the strongest during 11.85-11 Ma, the coldest period in 14-11 Ma as evidenced by the global deep-sea oxygen isotope records. Accordingly, we conclude that global climate cooled during MMCT and reached the coldest during 11.85-11 Ma. Thus, the westerly circulation became the strongest during this period, which brought more water vapor to Northwest China and the chemical weathering was significantly improved. On the other hand, the significant decrease in temperature led to the marked weakening of evapotranspiration, and thus the effective humidity was relatively increased. Both aspects contribute greatly to the significant enhancement of chemical weathering in eastern Central Asia. This weathering history of the sediments in the northeastern Tibetan Plateau is of great scientific significance to understanding tectonism and climate change in Asia during MMCT.

Smart-planes fetal heart (S-planes FH) software to quantitative evaluate the fetal great arteries.

OBJECTIVES: To explore the feasibility of applying smart-planes fetal heart (S-Planes FH) to 3D volumes to generate and display the outflow tract views (OFTVs) and evaluate its agreement and reliability in determining fetal vessel dimensions. METHODS: A total of 147 normal fetuses in the second or third trimester were enrolled. Once conventional 2D sonographic examination was finished, one or more 3D static volumes were then acquired in the 4-chamber view (4CV). The OFTVs automatically generated and displayed via a simple offline operation using S-Planes FH software. Per fetus, a single qualified S-Planes FH image was selected by an expert. The inner diameters of the aorta (AO) and pulmonary artery (PA) were measured in 2D and S-Planes FH images, respectively. The agreement and reliability of the two methods were verified by the Bland-Altman method and the intraclass correlation coefficient (ICC), respectively. RESULTS: A total of 515 3D static volumes were successfully acquired in 147 fetuses. The OFTVs were generated and displayed using S-Planes FH in 138 (93.9%) cases. S-Planes FH had good agreement in measuring the diameters of great arteries (95% CI of limits, -0.9419 to 1.1464 for AO diameter, -0.8871 to 1.7007 for PA diameter). The intraobserver and interobserver ICCs in this study were greater than 0.81, indicating almost perfect reliability of the two methods with regard to observers. CONCLUSIONS: S-Planes FH software is a feasible method for generating OFTVs as well as determining vessel dimensions in the second and third trimesters and had good agreement with 2D examination. Therefore, it possesses clinical value in screening for CHD and can be operated by different sonographers.

Response of tree rings to earthquakes during the past 350 years at Jiuzhaigou in the eastern Tibet.

Trees growing in the tectonically active and climatically sensitive regions, such as the Tibetan Plateau, frequently suffer damage from strong earthquakes and extreme hydro-climatic events. Spruce trees in the Jiuzhaigou National Park exhibited abrupt periods of growth suppression with durations of 3-9 years, which was demonstrated to have recorded five seismic events during the last 350 years after excluding the climatic impacts. The ring-width reductions occurred immediately after earthquakes in the growing seasons of 1748, 1879 and 2017, and one year later in 1961 when the earthquake occurred after the growing season in 1960. In contrast, seismic signals of the 1976 earthquake were moderated in the tree-ring indices by improved climatic conditions in 1975. The intensity prediction equation and isoseismal modelling results suggested that past earthquakes required a minimum intensity threshold of 6.2-6.8 MMI to significantly impact tree growth, thus indicating a minimum magnitude threshold of Mw5.3 for near-field (≤20 km) earthquakes and Mw7.4 for regional (≤115 km) earthquakes. These results would greatly improve the dendroseismological reconstruction of past earthquake characteristics and the valid assessment of future probabilities in the eastern Tibet, and help to identify and eliminate seismic signals in the dendroclimatological studies in the hazardous environments.

A novel 3-oxoacyl-ACP reductase (FabG3) is involved in the xanthomonadin biosynthesis of Xanthomonas campestris pv. campestris.

Xanthomonas campestris pv. campestris (Xcc), the causal agent of black rot in crucifers, produces a membrane-bound yellow pigment called xanthomonadin to protect against photobiological and peroxidative damage, and uses a quorum-sensing mechanism mediated by the diffusible signal factor (DSF) family signals to regulate virulence factors production. The Xcc gene XCC4003, annotated as Xcc fabG3, is located in the pig cluster, which may be responsible for xanthomonadin synthesis. We report that fabG3 expression restored the growth of the Escherichia coli fabG temperature-sensitive mutant CL104 under non-permissive conditions. In vitro assays demonstrated that FabG3 catalyses the reduction of 3-oxoacyl-acyl carrier protein (ACP) intermediates in fatty acid synthetic reactions, although FabG3 had a lower activity than FabG1. Moreover, the fabG3 deletion did not affect growth or fatty acid composition. These results indicate that Xcc fabG3 encodes a 3-oxoacyl-ACP reductase, but is not essential for growth or fatty acid synthesis. However, the Xcc fabG3 knock-out mutant abolished xanthomonadin production, which could be only restored by wild-type fabG3, but not by other 3-oxoacyl-ACP reductase-encoding genes, indicating that Xcc FabG3 is specifically involved in xanthomonadin biosynthesis. Additionally, our study also shows that the Xcc fabG3-disrupted mutant affects Xcc virulence in host plants.

The Cyclopropane Fatty Acid Synthase Mediates Antibiotic Resistance and Gastric Colonization of Helicobacter pylori.

Cyclopropane fatty acids (CFAs) are synthetized by the addition of a methylene group from S-adenosyl-l-methionine across the carbon-carbon double bonds of unsaturated fatty acid chains of membrane phospholipids. This fatty acid cyclopropanation, catalyzed by the CFA synthase (CfaS) enzyme, occurs in many bacteria, including the human pathogen Helicobacter pylori Although the cyclopropane modification was reported to play a key role in the adaptation in response to environmental stress, its role in H. pylori remains unknown. In this study, we showed that H. pylori HP0416 encodes a functional CfaS. The enzyme was demonstrated to be required for acid resistance, antibiotic resistance, intracellular survival and mouse gastric colonization, and cell membrane integrity. Moreover, the tool compound dioctylamine, which acts as a substrate mimic, directly inhibits the CfaS function of H. pylori, resulting into sensitivity to acid stress, increased antibiotic susceptibility, and attenuated abilities to avoid macrophage killing and to colonize mouse stomachs. These results validate CfaS as a promising antibiotic target and provide new potentials for this recognized target in future anti-H. pylori drug discovery efforts.IMPORTANCE The increasing prevalence of multidrug-resistant Helicobacter pylori strains has created an urgent need for alternative therapeutic regimens that complement the current antibiotic treatment strategies for H. pylori eradication; however, this is greatly hampered due to a lack of "druggable" targets. Although the CFAs are present in H. pylori cytoplasmic membranes at high levels, their physiological role has not been established. In this report, deletion of the CFA synthase CfaS was shown to attenuate acid and drug resistance, immune escape, and gastric colonization of H. pylori These findings were validated by inhibition of the CfaS activity with the tool compound dioctylamine. These studies identify this enzyme as an attractive target for further drug discovery efforts against H. pylori.

Characterization of 3-Oxacyl-Acyl Carrier Protein Reductase Homolog Genes in Pseudomonas aeruginosa PAO1.

Bacterial 3-oxoacyl-ACP reductase (OAR) catalyzes the 3-oxoacyl-ACP reduction step in the fatty acid synthesis pathway. At least 12 genes in the Pseudomonas aeruginosa genome are annotated as OAR-encoding genes. In this study, we characterized the functions of these genes with biochemical and genetic techniques. With the exception of PA2967, which encodes FabG, an essential protein in fatty acid synthesis, only the PA4389 and PA4786 gene products had OAR activity, and the single deletion of these two genes reduced the ability of P. aeruginosa to produce several specific quorum-sensing (QS) signals. However, PA4389 and PA4786 do not have key roles in fatty acid synthesis. Moreover, although most OAR homologs had no OAR activity, some may function in carbon utilization. The PA3128 product may play a role in the TCA cycle, and PA0182 and PA1470 seem to be required for the utilization of several amino acids. The rest of the OAR homologs have no roles in carbon utilization, but the deletion of one of these genes might affect the production of virulence factors by P. aeruginosa. We conclude that most OAR homolog genes do not encode OAR enzymes, and that these proteins do not function in fatty acid synthesis. IMPORTANCE: We report that although all P. aeruginosa OAR homologs have similar structures and the conserved catalytic triad of the bacterial OAR enzymes, only a few OAR homologs have OAR activity.

Novel Xanthomonas campestris Long-Chain-Specific 3-Oxoacyl-Acyl Carrier Protein Reductase Involved in Diffusible Signal Factor Synthesis.

The precursors of the diffusible signal factor (DSF) family signals of Xanthomonas campestris pv. campestris are 3-hydroxyacyl-acyl carrier protein (3-hydroxyacyl-ACP) thioesters having acyl chains of 12 to 13 carbon atoms produced by the fatty acid biosynthetic pathway. We report a novel 3-oxoacyl-ACP reductase encoded by the X. campestris pv. campestris XCC0416 gene (fabG2), which is unable to participate in the initial steps of fatty acyl synthesis. This was shown by the failure of FabG2 expression to allow growth at the nonpermissive temperature of an Escherichia colifabG temperature-sensitive strain. However, when transformed into the E. coli strain together with a plasmid bearing the Vibrio harveyi acyl-ACP synthetase gene (aasS), growth proceeded, but only when the medium contained octanoic acid. In vitro assays showed that FabG2 catalyzes the reduction of long-chain (≥C8) 3-oxoacyl-ACPs to 3-hydroxyacyl-ACPs but is only weakly active with shorter-chain (C4, C6) substrates. FabG1, the housekeeping 3-oxoacyl-ACP reductase encoded within the fatty acid synthesis gene cluster, could be deleted in a strain that overexpressed fabG2 but only in octanoic acid-supplemented media. Growth of the X. campestris pv. campestris ΔfabG1 strain overexpressing fabG2 required fabH for growth with octanoic acid, indicating that octanoyl coenzyme A is elongated by X. campestris pv. campestrisfabH Deletion of fabG2 reduced DSF family signal production, whereas overproduction of either FabG1 or FabG2 in the ΔfabG2 strain restored DSF family signal levels.IMPORTANCE Quorum sensing mediated by DSF signaling molecules regulates pathogenesis in several different phytopathogenic bacteria, including Xanthomonas campestris pv. campestris DSF signaling also plays a key role in infection by the human pathogen Burkholderia cepacia The acyl chains of the DSF molecules are diverted and remodeled from a key intermediate of the fatty acid synthesis pathway. We report a Xanthomonas campestris pv. campestris fatty acid synthesis enzyme, FabG2, of novel specificity that seems tailored to provide DSF signaling molecule precursors.

Serum angiopoietin-2 and ß-hCG as predictors of prolonged uterine bleeding after medical abortion in the first trimester.

OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We evaluate serum Angiopoietin-2 (Ang-2) and ß human chorionic gonadotropin (ß-hCG) in women who had undergone a medical abortion as markers of prolonged uterine bleeding (PUB). METHODS: Prospective trial involving 2843 women attending an gynecology outpatient clinic who following a medical abortion with mifepristone and misoprostol, the study cohort was divided into women with duration of uterine bleeding >14 days (PUB) and women with duration of uterine bleeding ≤14 days (normal uterine bleeding, NUB). Serum determinations of Ang-2 levels by ELISA and ß-hCG levels by electrochemiluminiscence immunoassay. Receiver Operating Characteristics (ROC) analyses were calculated and plotted for the diagnostic accuracy of serum ß-hCG and Ang-2 concentration to discriminate PUB and NUB. RESULTS: Baseline characteristics for both groups were similar, Only duration of bleeding showed a significant difference between the PUB group and NUB group. Ang-2 serum levels moderately correlated with serum ß-hCG levels with statistically significant correlation coefficients of 0.536. Serum ß-hCG and Ang-2 levels on day 7 and on day 14 after medical abortion were signifcantly higher in PUB group than in NUB group. Plotted as ROC curves, ß-hCG area under curve (AUC) was 0.65 (95% CI, 0.53-0.76) on day 7, rising to AUC = 0.83 (95% CI, 0.75-0.92) on day 14. Using Ang-2 on day 7 and day 14 as predictive parameter resulted in an analogous AUC (AUC = 0.61 on day 7, AUC = 0.78 on day 14). CONCLUSIONS: Both parameters are clinically useful as a diagnostic test in predicting PUB after medical abortion, and can be helpful in uncertain clinical situations, but should be considered as supplementary to a general clinical evaluation.