Comprehensive Utilization of Formation Water Scale to Prepare Controllable Size CaCO3 Nanoparticles: A New Method to Improve Oil Recovery.

Formation water scale blocks pipelines and results in oil/gas production decreasing and energy consumption increasing. Many methods have been developed to inhibit scale formation. However, these previous methods are limited by their complications and low efficiency. A new method is proposed in this paper that uses the scale in formation water as a nanomaterial to improve oil recovery via controlling particle size. A series of ligands were synthesized and characterized. Micrometer-CaCO3 was formed and accumulated to form scale of a large size under uncontrolled conditions. The tetradentate ligands (L4) exhibited an excellent capturing yield of Ca2+ (87%). The particle size was very small, but they accumulated to form large particles (approximately 1300 nm) in the presence of Na2CO3. The size of the CaCO3 could be further controlled by poly(aspartic acid) to form sizes of about 700 nm. The flooding test showed that this material effectively improved oil recovery from 55.2% without nano CaCO3 to 61.5% with nano CaCO3. This paves a new pathway for the utilization of Ca2+ in formation water.

Optimized microvascular decompression surgery for improving the results of hemifacial spasm: an analysis of reoperations.

Microvascular decompression (MVD) surgery is an effective curative treatment for hemifacial spasm (HFS). This study aims to establish techniques that may lead to favorable outcomes by analyzing reoperations in patients with persistent or recurrent HFS.Patients who exhibited persistent or recurrent HFS symptoms after prior MVD surgery were identified as candidates for reoperation. Information regarding the reoperations was collected by tracing the entire surgical procedures and peri-operative management. Clinical manifestations and follow-up data were obtained from the hospital records and subsequent visits.Twenty-six patients underwent repeat MVD surgery. Among them, multi-culprit neurovascular compression (NVC) was identified as the primary cause of failure to response to the previous operation in 73.08% of cases. Pure tissue adhesion accounted for 38.46% of cases, while shredded Teflon pledget (STP) shifting was observed in 7.69% of cases. Postoperative outcomes were assessed through revisits and categorized into four groups: excellent (76.92%), good (15.38%), fair (7.69%), and poor (0%). The longest follow-up period exceeded 65 moths.The trans-lateral suboccipital infra-floccular approach provides a better visual field. Examination of entire length of the facial nerve is essential. STP with gelatin sponge implantation is a suitable material for facilitating nerve and vascular positioning and reducing adhesion.

Association of triglyceride-glucose index with helicobacter pylori infection and mortality among the US population.

BACKGROUND: Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented. RESULTS: A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P < 0.05]. Furthermore, in patients with positive H. pylori infection, a noteworthy nonlinear correlation between the TyG index and all-cause mortality was identified (P = 0.0361). With an increase in the TyG index, all-cause mortality exhibited a corresponding rise, particularly following adjustment for all potential confounding factors. Conversely, in patients with negative H. pylori infection, no significant association was observed between the TyG index and all-cause mortality after adjusting for potential confounding factors. CONCLUSION: A higher TyG index was linked to increased H. pylori infection risks. Participants in the higher quantile group of the TyG index are positively associated with higher all-cause mortality compared to the higher quantile group of the TyG index in H. pylori-positive participants instead of H. pylori-negative participants.

Association of frailty index with all-cause and cardiovascular mortality with different diabetic status: NHANES 1999-2018.

AIMS: The relationship between frailty and mortality among individuals with varying diabetic statuses represents a burgeoning area of concern and scholarly interest within the medical community. However, there are limited studies that explore the relationship between frailty and mortality, as well as cause-specific mortality among individuals with non-diabetes, prediabetes, and diabetes patients. Hence, this study aims to investigate the relationship between the frailty statues and all-cause mortality, as well as cause-specific mortality in individuals with varying diabetic statuses using the data in the NHANES database. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 57, 098 participants. Both univariable and multivariable-adjusted logistic regression analyses, as well as Cox regression analysis were employed to examine the relationship between frailty index (FI) and mortality. RESULTS: This study, found a significant positive correlation between the frailty and the increased risk of all-cause mortality non-diabetic [OR 4.277, 95%CI (3.982, 4.594), P < 0.001], prediabetic [OR 2.312, 95%CI (2.133, 2.506), P < 0.001], and diabetic patients [OR 3.947, 95%CI (3.378, 4.611), P < 0.001]. This correlation still existed even after adjusting for confounding factors including age, sex, BMI, poverty, fasting insulin, education, smoke, alcohol drink, waist, hypertension, hyperlipidemia, fasting glucose, HbA1c, eGFR, creatinine and total bilirubin. Our result also suggested a significant positive correlation between the frailty index and the increased risk of CVD mortality among non-diabetic [OR 3.095, 95%CI (2.858, 3.352), P < 0.001] and prediabetic [OR 5.985, 95%CI (5.188, 6.904), P < 0.001] individuals. However, in patients with diabetes, the correlation between frailty and CVD mortality lost significance after adjusting for possible confounding factors [OR 1.139, 95%CI (0.794, 1.634), P > 0.05]. CONCLUSION: A nonlinear relationship has been identified between the FI and all-cause mortality, as well as CVD mortality in non-diabetic and pre-diabetic population. In diabetic patients, there was a significant positive correlation between the frailty and the increased risk of all-cause mortality, but not with CVD mortality. Renal function and liver function might potentially acted as an intermediary factor that elevated the risk of CVD mortality in frail patients with diabetes.

Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

A new subspecies of Aporia procris Leech, 1890 hidden in Sichuan, China (Lepidoptera, Pieridae).

Further information on the distribution of Aporia procris Leech, 1890 is provided. The population of A. procris from the upper Dadu River, W. Sichuan, previously recognized as ssp. yaozhui Huang, 2021, is treated as a new subspecies, viz., A. p. huangsiyaoi ssp. nov., based upon evidence from external features, with its genital and molecular characters given.

A new species of the genus Celaenorrhinus Hbner, [1819] from Hainan, China (Lepidoptera, Hesperiidae).

A new species, Celaenorrhinus qianhanae Li & Liu sp. nov., is described from Hainan, China. Its unique genital characteristics and wing markings are compared with other congeneric species from this island and adjacent regions, including Vietnam and China, etc. In addition, its COI gene is sequenced for molecular analysis, and the secondary sexual character, hair tufts on hind tibiae, is discussed for comparison.

Discovery of novel Akt1 inhibitors by an ensemble-based virtual screening method, molecular dynamics simulation, and in vitro biological activity testing.

Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

Discovery of novel S6K1 inhibitors by an ensemble-based virtual screening method and molecular dynamics simulation.

Ribosomal protein S6 kinase beta-1 (S6K1) is considered a potential target for the treatment of various diseases, such as obesity, type II diabetes, and cancer. Development of novel S6K1 inhibitors is an urgent and important task for the medicinal chemists. In this research, an effective ensemble-based virtual screening method, including common feature pharmacophore model, 3D-QSAR pharmacophore model, naïve Bayes classifier model, and molecular docking, was applied to discover potential S6K1 inhibitors from BioDiversity database with 29,158 compounds. Finally, 7 hits displayed considerable properties and considered as potential inhibitors against S6K1. Further, carefully analyzing the interactions between these 7 hits and key residues in the S6K1 active site, and comparing them with the reference compound PF-4708671, it was found that 2 hits exhibited better binding patterns. In order to further investigate the mechanism of the interactions between 2 hits and S6K1 at simulated physiological conditions, the molecular dynamics simulation was performed. The ΔGbind energies for S6K1-Hit1 and S6K1-Hit2 were - 111.47 ± 1.29 and - 54.29 ± 1.19 kJ mol-1, respectively. Furthermore, deep analysis of these results revealed that Hit1 was the most stable complex, which can stably bind to S6K1 active site, interact with all of the key residues, and induce H1, H2, and M-loop regions changes. Therefore, the identified Hit1 may be a promising lead compound for developing new S6K1 inhibitor for various metabolic diseases treatment.

Discovery of potent microtubule-destabilizing agents targeting for colchicine site by virtual screening, biological evaluation, and molecular dynamics simulation.

Microtubule has been considered as attractive therapeutic target for various cancers. Although numerous of chemically diverse compounds targeting to colchicine site have been reported, none of them was approved by Food and Drug Administration. In this investigation, the virtual screening methods, including pharmacophore model, molecular docking, and interaction molecular fingerprints similarity, were applied to discover novel microtubule-destabilizing agents from database with 324,474 compounds. 22 compounds with novel scaffolds were identified as microtubule-destabilizing agents, and then submitted to the biological evaluation. Among these 22 hits, hit4 with novel scaffold represents the best anti-proliferative activity with IC50 ranging from 4.51 to 14.81 µM on four cancer cell lines. The in vitro assays reveal that hit4 can effectively inhibit tubulin assembly, and disrupt the microtubule network in MCF-7 cell at a concentration-dependent manner. Finally, the molecular dynamics simulation analysis exhibits that hit4 can stably bind to colchicine site, interact with key residues, and induce αT5 and ßT7 regions changes. The values of ΔGbind for the tubulin-colchicine and tubulin-hit4 are -172.9±10.5 and -166.0±12.6 kJ·mol-1, respectively. The above results indicate that the hit4 is a novel microtubule destabilizing agent targeting to colchicine-binding site, which could be developed as a promising tubulin polymerization inhibitor with higher activity for cancer therapy.

Satisfaction and its determinants of rural upper gastrointestinal cancer screening in China: a preliminary cross-sectional study.

OBJECTIVES: To assess participants' satisfaction with and predictors of upper gastrointestinal cancer screening in rural areas. DESIGN: Cross-sectional study. SETTING: Ten screening centres in seven cities across five provinces in China. PARTICIPANTS: Of the 452 participants screened during the survey period, 438 completed the survey (response rate: 96.90%). PRIMARY OUTCOME MEASURES: Screening satisfaction was the primary outcome and it was assessed using the Patient Satisfaction Questionnaire-18. Ordinal logistic regression analysis was used to analyse the predictors of satisfaction. RESULTS: The percentages of satisfaction with the General Satisfaction, Technical Quality, Interpersonal Manner, Communication, Financial Aspects, Time Spent With Doctor, and Convenience and Accessibility dimensions were 95.89%, 79.68%, 88.36%, 83.56%, 75.11%, 82.19% and 66.44%, respectively. Education (OR 0.25, 95% CI 0.07 to 0.90), health self-assessment (OR 15.29, 95% CI 2.86 to 81.78) and family history of cancer (OR 4.20, 95% CI 1.29 to 13.71) were associated with General Satisfaction. Residence (OR 4.31, 95% CI 1.89 to 9.81) was associated with Technical Quality. Occupation (OR 0.27, 95% CI 0.08 to 0.88), health self-assessment (OR 11.30, 95% CI 3.94 to 32.43), screening purpose (OR 0.18, 95% CI 0.03 to 0.92) and distance from the screening centre (OR 4.59, 95% CI 1.35 to 15.61) were associated with interpersonal manner. Gender (OR 1.85, 95% CI 1.02 to 3.34), residence (OR 3.23, 95% CI 1.23 to 8.53) and endoscopy in the previous year (OR 2.79, 95% CI 1.13 to 6.90) were associated with Communication. Body mass index (BMI; OR 5.06, 95% CI 1.40 to 18.25) and health self-assessment (OR 2.09, 95% CI 1.12 to 3.88) were associated with financial aspects. Gender (OR 1.90, 95% CI 1.07 to 3.38), residence (OR 3.19, 95% CI 1.30 to 7.79), BMI (OR 5.26, 95% CI 1.14 to 24.34) and health self-assessment (OR 2.14, 95% CI 1.06 to 4.34) were associated with time spent with doctor. Gender (OR 1.64, 95% CI 1.04 to 2.60) and residence (OR 3.17, 95% CI 1.46 to 6.88) were associated with convenience and accessibility. CONCLUSION: There was heterogeneity across the dimensions of satisfaction with rural upper gastrointestinal cancer screening. Project manager should prioritise improving the aspects related to the convenience and accessibility dimension. Furthermore, to improve the efficiency of potential interventions, the predictors of the various dimensions should be considered.

Notes on Stibochiona nicea (Gray, 1846) from China with description of a new subspecies from Hainan Island (Lepidoptera, Nymphalidae).

New information of Stibochiona nicea is presented. Stibochiona nicea wangyukunae ssp. nov. is described from Hainan Island, S. China based on wing patterns, and S. nicea subucula is recorded from China for the first time. The adults and the male genitalia of all the three subspecies of N. nicea from China are illustrated.

Environmental filtering drives the establishment of the distinctive rhizosphere, bulk, and root nodule bacterial communities of Sophora davidii in hilly and gully regions of the Loess Plateau of China.

In addition to the rhizobia, other non-rhizobial endophytes (NREs) have been simultaneously isolated from the root nodules. The existence of NREs in leguminous root nodules is a universal phenomenon, and they have the potential to enhance legume survival, especially under conditions of environmental stress. However, the diversity and biogeographic patterns of microbial communities inhabiting root nodules are not well studied or understood. Here, we explored and characterized the diversity of NRE bacteria by using 16S rRNA gene high-throughput amplicon sequencing. Additionally, we compared the biogeography and co-occurrence patterns in review of the bacterial microbiota inhabiting the rhizosphere, the bulk soil and the root nodule bacterial communities associated with Sophora davidii, a native N-fixing wild leguminous shrub in hilly and gully regions of the Loess Plateau of China. The results showed the presence of a large diversity of bacteria belonging to 81 phyla, 154 classes, 333 orders, 463 families, and 732 genera inside the nodules. Proteobacteria were dominant in the nodule and rhizosphere soil samples, and Actinomycetes were dominant in the bulk soil samples. Mesorhizobium was the dominant genus in the nodules, accounting for between 60.15 and 83.74% of the bacteria. The microbial community composition of the NRE in the root nodules differed from that in the rhizosphere soil and the bulk soil of S. davidii. Moreover, we found that the biogeographic patterns and assembly process of the rhizobia and non-rhizobia communities differed in the root nodule, the rhizosphere soil and the bulk soil. Furthermore, the correlation analysis between the soil's physical and chemical properties and the bacteria showed that available phosphorus was the predominant factor affecting the bacterial diversity within the rhizosphere soil. Finally, our results revealed that the microbial network diagram of co-occurrence patterns showed more complexes in the soil than in the root nodules. This indicates that only specific microorganisms could colonize and thrive in the rhizosphere through the selection and filtering effects of roots. In conclusion, there are significant differences in bacterial community composition in the nodules, rhizosphere and bulk soil in the hilly and gully region of the Loess Plateau, which is the result of environmental filtration. Our study improves the understanding of the biogeographic patterns and diversity of bacterial microbiota inhabiting root nodules and can help quantify and define the root nodule assemblage process of S. davidii.

Identification of Novel Inhibitors Targeting SGK1 via Ensemble-Based Virtual Screening Method, Biological Evaluation and Molecular Dynamics Simulation.

Serum and glucocorticoid-regulated kinase 1 (SGK1), as a serine threonine protein kinase of the AGC family, regulates different enzymes, transcription factors, ion channels, transporters, and cell proliferation and apoptosis. Inhibition of SGK1 is considered as a valuable approach for the treatment of various metabolic diseases. In this investigation, virtual screening methods, including pharmacophore models, Bayesian classifiers, and molecular docking, were combined to discover novel inhibitors of SGK1 from the database with 29,158 compounds. Then, the screened compounds were subjected to ADME/T, PAINS and drug-likeness analysis. Finally, 28 compounds with potential inhibition activity against SGK1 were selected for biological evaluation. The kinase inhibition activity test revealed that among these 28 hits, hit15 exhibited the highest inhibition activity against SGK1, which gave 44.79% inhibition rate at the concentration of 10 µM. In order to further investigate the interaction mechanism of hit15 and SGK1 at simulated physiological conditions, a molecular dynamics simulation was performed. The molecular dynamics simulation demonstrated that hit15 could bind to the active site of SGK1 and form stable interactions with key residues, such as Tyr178, ILE179, and VAL112. The binding free energy of the SGK1-hit15 was -48.90 kJ mol-1. Therefore, the identified hit15 with novel scaffold may be a promising lead compound for development of new SGK1 inhibitors for various diseases treatment.

Development of binary classification models for assessment of drug-induced liver injury in humans using a large set of FDA-approved drugs.

Drug-induced liver injury (DILI) has been identified as one of the major causes for drugs withdrawn from the market, and even termination during the late stages of development. Therefore, it is imperative to evaluate the DILI potential of lead compounds during the research and development process. Although various computational models have been developed to predict DILI, most of which applied the DILI data were extracted from preclinical sources. In this investigation, the in silico prediction models for DILI were constructed based on 1140 FDA-approved drugs by using naïve Bayes classifier approach. The genetic algorithm method was applied for the molecular descriptors selection. Among these established prediction models, the NB-11 model based on eight molecular descriptors combined with ECFP_18 showed the best prediction performance for DILI, which gave 91.7% overall prediction accuracy for the training set, and 68.9% concordance for the external test set. Therefore, the established NB-11 prediction model can be used as a reliable virtual screening tool to predict DILI adverse effect in the early stages of drug design. In addition, some new structural alters for DILI were identified, which could be used for structural optimization in the future drug design by medicinal chemists.

Discovery of novel microtubule stabilizers targeting taxane binding site by applying molecular docking, molecular dynamics simulation, and anticancer activity testing.

Disruption of the dynamic equilibrium of microtubules can induce cell cycle arrest in G2/M phase and apoptosis. Hence, discovery of novel tubulin polymerization inhibitors is very necessary and an important task in drug research and development for treatment of various tumors. In this investigation, 50 compounds were screened as microtubule stabilizers targeting the taxane site by combination of molecular docking methods. Among these hits, hits 19 and 38 with novel scaffolds exhibited the highest anti-proliferative activity with IC50 ranging from 9.50 to 13.81 µM in four cancer cell lines. The molecular dynamics simulations confirmed that tubulin and two hits could form stable systems. Meanwhile, the mechanism of the interactions between tubulin and two hits at simulated physiological conditions were probed. The in vitro tubulin polymerization assay revealed hits 19 and 38 were able to promote tubulin polymerization in a dose-dependent manner. Further, the immunofluorescence assay suggested that hits 19 and 38 could accelerate microtubule assembly in A549 and HeLa cells. Finally, studies on antitumor activity indicated that hits 19 and 38 induced G2/M phase cell cycle arrest and apoptosis, and inhibited cancer cell motility and migration in A549 and HeLa cells. Importantly, hit38 exhibited better anti-tubulin and anti-cancer activity than hit19 in A549 and HeLa cells. Therefore, these results suggest that hit38 represents a promising microtubule stabilizer for treating cancer and deserves further investigation.

Evaluation on the Performance of Hydraulic Bitumen Binders under High and Low Temperatures for Pumped Storage Power Station Projects.

The high and low-temperature performance of five hydraulic bitumen binders was evaluated using the dynamic shear rheometer (DSR) test, infrared spectrum test and direct tensile (DT) test. These hydraulic bitumen binders were respectively applied for several pumped storage power stations (PSPS) projects that were constructed or under construction. In order to relate the bitumen performance to the mixture performance, the slope flow test, three-point bending test and thermal stress restrained specimen test were carried out on hydraulic asphalt mixtures. The test results indicated the DSR rheological master curves can well distinguish the difference of each bitumen binder as well as the effect of polymer modification. Phase angle master curves, black diagrams and infrared spectra all indicated that several penetration-grade hydraulic bitumen binders were not virgin bitumen binders but were modified with relatively lower SBS polymer content when compared with traditional SBS-modified bitumen. When selecting the commonly used Karamay SG70 hydraulic bitumen as a reference, the normal SBS-modified bitumen was superior to other bitumen in terms of low- and high-temperature performance. Several slightly SBS-modified bitumen binders did not always show consistent results, which indicated that slightly modified bitumen may not really have the desired performance as expected. Therefore, SBS-modified bitumen will be more promising when dealing with extremely low or high temperatures. Bitumen performance was well compared with the mixture performance by using the bitumen creep, relaxation and tensile failure strain corresponding to the asphalt concrete slope flow, the maximum bending strain and the failure temperature, respectively. Compared with the traditional penetration, softening point and ductility test, it indicated that the DSR rheological test, creep test, direct tensile test and stress relaxation test can be used as more powerful tools for the characterization and optimization of hydraulic bitumen binders.

Discovery of microtubule stabilizers with novel scaffold structures based on virtual screening, biological evaluation, and molecular dynamics simulation.

Disrupting the dynamics and structures of microtubules can perturb mitotic spindle formation, cause cell cycle arrest in G2/M phase, and subsequently lead to cellular death via apoptosis. In this investigation, the structure-based virtual screening methods, including molecular docking and rescoring, and similarity analysis of interaction molecular fingerprints, were developed to discover novel tubulin inhibitors from ChemDiv database with 1,601,806 compounds. The screened compounds were further filtered by PAINS, ADME/T, Toxscore, SAscore, and Drug-likeness analysis. Finally, 17 hit compounds were selected, and then submitted to the biologic evaluation. Among these hits, the P2 exhibited the strongest antiproliferative activity against four tumor cells including HeLa, HepG2, MCF-7, and A549. The in vitro tubulin polymerization assay revealed P2 could promote tubulin polymerization in a dose dependent manner. Finally, in order to analyze the interaction modes of complexes, the molecular dynamics simulation was performed to investigate the interactions between P2 and tubulin. The molecular dynamics simulation analysis showed that P2 could stably bind to taxane site, induced H6-H7, B9-B10, and M-loop regions changes. The ΔGbind energies of tubulin-P2 and tubulin-paclitaxel were -68.25 ± 12.98 and -146.05 ± 16.17 kJ mol-1, respectively, which were in line with the results of the experimental test. Therefore, P2 has been well characterized as lead compounds for developing new tubulin inhibitors with potential anticancer activity.

High Central Venous Pressure and Right Ventricle Size Are Related to Non-decreased Left Ventricle Stroke Volume After Negative Fluid Balance in Critically Ill Patients: A Single Prospective Observational Study.

Background: Optimal adjustment of cardiac preload is essential for improving left ventricle stroke volume (LVSV) and tissue perfusion. Changes in LVSV caused by central venous pressure (CVP) are the most important concerns in the treatment of critically ill patients. Objectives: This study aimed to clarify the changes in LVSV after negative fluid balance in patients with elevated CVP, and to elucidate the relationship between the parameters of right ventricle (RV) filling state and LVSV changes. Methods: This prospective cohort study included patients with high central venous pressure (CVP) (≥8 mmHg) within 24 h of ICU admission in the Critical Medicine Department of Peking Union Medical College Hospital. Patients were classified into two groups based on the LVSV changes after negative fluid balance. The cutoff value was 10%. The hemodynamic and echo parameters of the two groups were recorded at baseline and after negative fluid balance. Results: A total of 71 patients included in this study. Forty in VI Group (LVOT VTI increased ≥10%) and 31 in VNI Group (LVOT VTI increased <10%). Of all patients, 56.3% showed increased LVSV after negative fluid balance. In terms of hemodynamic parameters at T0, patients in VI Group had a higher CVP (p < 0.001) and P(v-a)CO2 (p < 0.001) and lower ScVO2 (p < 0.001) relative to VNI Group, regarding the echo parameters at T0, the RVD/LVD ratio (p < 0.001), DIVC end-expiratory (p < 0.001), and ΔLVOT VTI (p < 0.001) were higher, while T0 LVOT VTI (p < 0.001) was lower, in VI Group patients. The multifactor logistic regression analysis suggested that a high CVP and RVD/LVD ratio ≥0.6 were significant associated with LVSV increase after negative fluid balance in critically patients. The AUC of CVP was 0.894. A CVP >10.5 mmHg provided a sensitivity of 87.5% and a specificity of 77.4%. The AUC of CVP combined with the RVD/LVD ratio ≥0.6 was 0.926, which provided a sensitivity of 92.6% and a specificity of 80.4%. Conclusion: High CVP and RVD/LVD ratio ≥0.6 were significant associated with RV stressed in critically patients. Negative fluid balance will not always lead to a decrease, even an increase, in LVSV in these patients.