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Abstract We investigate the subleading-power corrections to the exclusive B → Dℓν ℓ form factors at O $$ \mathcal{O} $$ ( α s 0 $$ {\alpha}_s^0 $$ ) in the light-cone sum rules (LCSR) framework by including the two- and three-particle higher-twist contributions from the B-meson light-cone distribution amplitudes up to the twist-six accuracy, by taking into account the subleading terms in expanding the hard-collinear charm-quark propagator, and by evaluating the hadronic matrix element of the subleading effective current . Employing further the available leading-power results for the semileptonic B → D form factors at the next-to- leading-logarithmic level and combining our improved LCSR predictions with the recent lattice determinations, we then carry out a comprehensive phenomenological analysis on the semi-leptonic B → Dℓν ℓ decay. We extract V cb = 40.2 − 0.5 + 0.6 th − 1.4 + 1.4 exp × 10 − 3 V cb = 40.9 − 0.5 + 0.6 th − 1.0 + 1.0 exp × 10 − 3 $$ \left|{V}_{cb}\right|=\left({40.2}_{-0.5}^{+0.6}{\left|{{}_{\mathrm{th}}}_{-1.4}^{+1.4}\right|}_{\mathrm{exp}}\right)\times {10}^{-3}\left(\left|{V}_{cb}\right|=\left({40.9}_{-0.5}^{+0.6}{\left|{{}_{\mathrm{th}}}_{-1.0}^{+1.0}\right|}_{\mathrm{exp}}\right)\times {10}^{-3}\right) $$ using the BaBar (Belle) experimental data, and particularly obtain for the gold-plated ratio R(D) = 0.302 ± 0.003.

Abstract Background High-intensity noninvasive positive pressure ventilation (NPPV) is a novel ventilatory approach to maximally decreasing elevated arterial carbon dioxide tension (PaCO2) toward normocapnia with stepwise up-titration of pressure support. We tested whether high-intensity NPPV is more effective than low-intensity NPPV at decreasing PaCO2, reducing inspiratory effort, alleviating dyspnoea, improving consciousness, and improving NPPV tolerance in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods In this physiological, randomised controlled trial, we assigned 24 AECOPD patients to undergo either high-intensity NPPV (n = 12) or low-intensity NPPV (n = 12). The primary outcome was PaCO2 24 h after randomisation. Secondary outcomes included gas exchange other than PaCO2 24 h after randomisation, inspiratory effort, dyspnoea, consciousness, NPPV tolerance, patient–ventilator asynchrony, cardiac function, ventilator-induced lung injury (VILI), and NPPV-related adverse events. Results Inspiratory positive airway pressure 24 h after randomisation was significantly higher (28.0 [26.0–28.0] vs. 15.5 [15.0–17.5] cmH2O; p = 0.000) and NPPV duration within the first 24 h was significantly longer (21.8 ± 2.1 vs. 15.3 ± 4.7 h; p = 0.001) in the high-intensity NPPV group. PaCO2 24 h after randomisation decreased to 54.0 ± 11.6 mmHg in the high-intensity NPPV group but only decreased to 67.4 ± 10.6 mmHg in the low-intensity NPPV group (p = 0.008). Inspiratory oesophageal pressure swing, oesophageal pressure–time product (PTPes)/breath, PTPes/min, and PTPes/L were significantly lower in the high-intensity group. Accessory muscle use and dyspnoea score 24 h after randomisation were also significantly lower in that group. No significant between-groups differences were observed in consciousness, NPPV tolerance, patient–ventilator asynchrony, cardiac function, VILI, or NPPV-related adverse events. Conclusions High-intensity NPPV is more effective than low-intensity NPPV at decreasing elevated PaCO2, reducing inspiratory effort, and alleviating dyspnoea in AECOPD patients. Trial registration: ClinicalTrials.gov (NCT04044625; registered 5 August 2019).

Abstract Background This study was designed to investigate the extent to which physicians involved in sepsis management understand and adopt sepsis guidelines in clinical practice. The overarching aim of this study was to generate ideas for developing more effective training methods to help physicians apply the guidelines in patient management. Methods Physicians working in a tertiary care hospital, primarily in the emergency and critical care departments, were recruited into the survey. They were asked to fill questionnaires which were designed to collect sepsis score, diagnostic indicators, fluid resuscitation, antibiotics choice, access to knowledge and training, as well as implementation of sepsis guidelines in clinical diagnosis and treatment. Results Overall, the response rate was 625/661 (94.5%). The investigate shows the basic information of all physicians who participated in the answer sheet, including their work department, professional title and whether their hospital was a teaching hospital. Significant differences were identified among the physicians in terms of method of acquiring sepsis guidelines, the impact of study guidelines on clinical diagnosis and treatment, efficiency of training methods, cognition of fluid resuscitation in patients with sepsis, the cognition of sepsis rehydration principles, selection of antibiotics for patients with sepsis, the basis for antibiotic selection, among other variables. Conclusion Although majority of physicians involved in tertiary care hospital understand the contents of sepsis-3 guidelines, the clinical implementation of the guidelines in the diagnosis and treatment of patients with sepsis is highly heterogeneous. Thus, there is need to develop standardized training for physicians involved in sepsis diagnosis and treatment.

Background Osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) could be administered sequentially to promote tendon-bone healing. There remain several unresolved issues in our previously published study: a) the release kinetics of OPG/BMP-2 from the OPG/BMP-2/collagen sponge (CS) combination in vitro remained unclear; b) the medium-term effect of the OPG/BMP-2/CS combination was not analyzed. Hence, we design this study to address the issues mentioned above. Methods 30 rabbits undergoing anterior cruciate ligament reconstruction (ACLR) with an Achilles tendon autograft randomly received one of the 3 delivery at the femoral and tibial tunnels: OPG/BMP-2, OPG/BMP-2/CS combination, and nothing (blank control). At 8 and 24 weeks post-surgery, the biomechanical tests and histologic analysis were used to evaluate the tendon-bone healing. Results In mechanical tests, the OPG/BMP-2/CS group showed a higher final failure load and stiffness than the other groups at 8 and 24 weeks. Additionally, the maximum stretching distance showed a decreasing trend. The mechanical failure pattern of samples shifted from a tunnel pull-away to a graft midsubstance rupture after OPG/BMP-2/CS-treated. From histological analysis, the OPG/BMP-2/CS treatment increased the amount of collagen fibers (collagen I and II) and promoted fibrocartilage attachment. Conclusion CS as a carrier promotes the medium-term effect of OPG and BMP-2 on tendon-bone healing at the tendon-bone interface in a rabbit ACLR model. OPG, BMP-2 and CS were already applied in several clinical practice, but a further study of clinic use of OPG/BMP-2/CS is still needed.

Postmenopausal osteoporosis (PMOP) is a common bone disease characterized by decreased bone density and increased bone fragility due to decreased estrogen levels. Qiangguyin (QGY) is transformed from the famous traditional Chinese medicine BuShen Invigorating Blood Decoction. In this study, we used QGY to treat PMOP. We observed that QGY significantly reduced fat accumulation in the chondro-osseous junction. However, its specific mechanism of action remains unclear. To determine the specific molecular mechanism of QGY, we explored the pharmacological mechanism by which QGY reduces fat accumulation in the chondro-osseous junction through network pharmacological analysis. The active components and targets related to PMOP and QGY were screened from different databases, forming a composition-target-disease network. Next, a comprehensive analysis platform including protein-protein interaction (PPI) network, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were established. The results revealed that QGY inhibits adipogenic differentiation by activating the mitogen-activated protein kinase (MAPK) signaling pathway, thus reducing the accumulation of fat in the chondro-osseous junction. For further verification. In vitro and in vivo experiments were carried out. Our data showed that QGY significantly reversed the high expression of fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor γ (PPARγ). Further, QGY prevents fat accumulation by inhibiting the expression of p38. In summary, the results of this study suggested that QGY-induced phenotypic changes are related to the activation of the p38 MAPK signaling pathway.

Abstract Employing the QCD factorization formalism we compute B u − → γ ∗ ℓ v ¯ ℓ $$ {B}_u^{-}\to {\gamma}^{\ast}\mathrm{\ell}{\overline{v}}_{\mathrm{\ell}} $$ form factors with an off-shell photon state possessing the virtuality of order m b ΛQCD and m b 2 $$ {m}_b^2 $$ , respectively, at next-to-leading order in QCD. Perturbative resummation for the enhanced logarithms of m b /ΛQCD in the resulting factorization formulae is subsequently accomplished at next-to-leading logarithmic accuracy with the renormalization-group technique in momentum space. In particular, we derive the soft-collinear factorization formulae for a variety of the subleading power corrections to the exclusive radiative B u − → γ ∗ W ∗ $$ {B}_u^{-}\to {\gamma}^{\ast }{W}^{\ast } $$ form factors with a hard-collinear photon at O α s 0 $$ \mathcal{O}\left({\alpha}_s^0\right) $$ . We further construct a complete set of the angular observables governing the full differential distribution of the four-body leptonic decays B u − → ℓ ′ ℓ ¯ ′ ℓ v ¯ ℓ $$ {B}_u^{-}\to {\mathrm{\ell}}^{\prime }{\overline{\mathrm{\ell}}}^{\prime}\mathrm{\ell}{\overline{v}}_{\mathrm{\ell}} $$ with ℓ, ℓ′ ∈ {e, μ} and then perform an exploratory phenomenological analysis for a number of decay observables accessible at the LHCb and Belle II experiments, with an emphasis on the systematic uncertainties arising from the shape parameters of the leading-twist B-meson light-cone distribution amplitude in heavy quark effective theory.

Lithium, a representative alkali metal, holds the coveted status of the ‘‘holy grail’’ in the realm of nextgeneration rechargeable batteries, owing to its remarkable theoretical specific capacity and low electrode potential. However, the inherent reactivity of Li metal inevitably results in the formation of the solid–electrolyte interphase (SEI) on its surface, adding complexity to the Li electrodeposition process compared to conventional metal electrodeposition. Attaining uniform Li deposition is crucial for ensuring stable, long-cycle performance and high Coulombic efficiency in Li metal batteries, which requires a comprehensive understanding of the underlying factors governing the electrodeposition process. This review delves into the intricate kinetics of Li electrodeposition, elucidating the multifaceted factors that influence charge and mass transfer kinetics. The intrinsic relationship between charge transfer kinetics and Li deposition is scrutinized, exploring how parameters such as current density and electrode potential impact Li nucleation and growth, as well as dendrite formation. Additionally, the applicability of classical mass-transfer-controlled electrodeposition models to Li anode systems is evaluated, considering the influence of ionic concentration and solvation structure on Li+ transport, SEI formation, and subsequent deposition kinetics. The pivotal role of SEI compositional structure and physicochemical properties in governing charge and mass transfer processes is underscored, with an emphasis on strategies for regulating Li deposition kinetics from both electrolyte and SEI perspectives. Finally, future directions in Li electrodeposition research are outlined, emphasizing the importance of ongoing exploration from a kinetic standpoint to fully unlock the potential of Li metal batteries. [ABSTRACT FROM AUTHOR]

Background Iron deficiency is the leading cause of anaemia worldwide and frequently observed in adolescent women, particularly those with eating disorders like anorexia nervosa. Consequently, clinicians may overlook iron deficiency anaemia, potentially missing a more serious diagnosis. Case summary A 19-year-old woman was referred to the hospital by her general practitioner due to worsening symptomatic iron deficiency anaemia, despite treatment with oral iron supplementation. Her blood cultures consistently grew Streptococcus sanguinis , and an echocardiogram revealed vegetations on the mitral and tricuspid valves, confirming the diagnosis of infective endocarditis. Several systemic complications of varying acuity were identified, including a ruptured left common iliac artery aneurysm with active haemorrhage into the left psoas muscle, enlarging cerebral, hepatic, and right common femoral artery aneurysms, splenic infarction with abscess formation, and an infected left psoas muscle haematoma. Multimodal imaging and collaboration within the multidisciplinary endocarditis team were crucial for coordinating further evaluation and managing the complex array of peripheral lesions in infective endocarditis. The patient was discharged with a good clinical outcome after 81 days. Discussion This case highlights the risks of overlooking iron deficiency anaemia in adolescent women with anorexia nervosa and the serious consequences of untreated complicated infective endocarditis. It emphasizes the need for thorough investigation of anorexia nervosa patients for infections due to their reduced clinical response, to ensure early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Construction and agricultural waste recycling have gained more and more attention recently as renewable resources. Straw and construction waste, both of which are widespread in northern Fujian, were investigated in this research. The orthogonal test was used to investigate the effects of recycled aggregate, straw, and glazed hollow beads on the mechanical and thermal properties of recycled insulation concrete. The influence of different factors on the macroscopic characteristics of recycled insulation concrete was examined using scanning electron microscopy (SEM). The optimal mix proportion for recycled insulation concrete that satisfies mechanical performance standards and provides superior insulation performance was then determined using the total efficacy coefficient method. According to the research findings, the heat conductivity of recycled insulation concrete decreases as its dried density decreases. A 100% recycled coarse aggregate replacement rate, 1% straw content, and 10% glazed hollow beads replacement rate are the optimal mix ratios for recycled insulation concrete. With a compressive strength of 20.98 MPa, a splitting tensile strength of 2.01 MPa, a thermal conductivity of 0.3776 W/(m·K), and a dry density of 1778.66 kg/m3, recycled insulation concrete has the optimal mix ratio. Recycled insulation concrete is a novel form of eco-friendly, energy-saving concrete that aims to achieve low-carbon energy savings and sustainable development by combining resource recycling with building energy savings to realize the recycling of solid waste resources, which has significant environmental, social, and economic benefits and broad market application potential.

This study aims to develop a finite difference time-domain (FDTD) modeling method for complex terrain using a paper contour map. First, the image preprocessing technology is employed to segment, denoise, and number the drawing area to arrive at independent figures and curve matrices. Subsequently, the support vector machine (SVM) classifier is implemented to identify the number and obtain the elevation value pertinent to the curve in the figure. Finally, the scattered points in the curve matrix are meshed by the Delaunay triangulation algorithm, and a three-dimensional triangular mesh model is established according to the recognition results. The FDTD calculation model is established by the method of intersection of Yee cell grid lines and triangle projection. The simulation results reveal that the recognition rate of the SVM classification model in this study is close to 100% for printed numerals. This approach is capable of quickly and accurately establishing the FDTD-based calculation model for complex terrain on the basis of the paper contour map.

Abstract Background High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. Methods In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. Results HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P

Traditional chemotherapy exhibits a certain therapeutic effect toward malignant cancer, but easily induce tumor multidrug resistance (MDR), thereby resulting in the progress of tumor recurrence or metastasis. In this work, we deigned ternary hybrid nanodrugs (PEI/DOX@CXB-NPs) to simultaneously combat against tumor MDR and metastasis. In vitro results demonstrate this hybrid nanodrugs could efficiently increase cellular uptake at pH 6.8 by the charge reversal, break lysosomal sequestration by the proton sponge effect and trigger drugs release by intracellular GSH, eventually leading to higher drugs accumulation and cell-killing in drug-sensitive/resistant cells. In vivo evaluation revealed that this nanodrugs could significantly inhibit MDR tumor growth and simultaneously prevent A549 tumor liver/lung metastasis owing to the specifically drugs accumulation. Mechanism studies further verified that hybrid nanodrugs were capable of down-regulating the expression of MDR or metastasis-associated proteins, lead to the enhanced anti-MDR and anti-metastasis effect. As a result, the multiple combination strategy provided an option for effective cancer treatment, which could be potentially extended to other therapeutic agents or further use in clinical test.

Sorting out organic molecules with high thermopower is essential for understanding molecular thermoelectrics. The intermolecular coupling offers a unique chance to enhance the thermopower by tuning the bandgap structure of molecular devices, but the investigation of intermolecular coupling in bulk materials remains challenging. Herein, we investigated the thermopower of diketopyrrolopyrrole (DPP) cored single-molecule junctions with different coupling strengths by varying the packing density of the self-assembled monolayers (SAM) using a customized scanning tunneling microscope break junction (STM-BJ) technique. We found that the thermopower of DPP molecules could be enhanced up to one order of magnitude with increasing packing density, suggesting that the thermopower increases with larger neighboring intermolecular interactions. The combined density functional theory (DFT) calculations revealed that the closely-packed configuration brings stronger intermolecular coupling and then reduces the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, leading to an enhanced thermopower. Our findings offer a new strategy for developing organic thermoelectric devices with high thermopower.

Background: Chronic kidney disease (CKD), characterized by sustained inflammation and immune dysfunction, is highly prevalent and can eventually progress to end-stage kidney disease. However, there is still a lack of effective and reliable diagnostic markers and therapeutic targets for CKD.Methods: First, we merged data from GEO microarrays (GSE104948 and GSE116626) to identify differentially expressed genes (DEGs) in CKD and healthy patient samples. Then, we conducted GO, KEGG, HPO, and WGCNA analyses to explore potential functions of DEGs and select clinically significant modules. Moreover, STRING was used to analyse protein-protein interactions. CytoHubba and MCODE algorithms in the cytoscape plug-in were performed to screen hub genes in the network. We then determined the diagnostic significance of the obtained hub genes by ROC and two validation datasets. Meanwhile, the expression level of the biomarkers was verified by IHC. Furthermore, we examined immunological cells’ relationships with hub genes. Finally, GSEA was conducted to determine the biological functions that biomarkers are significantly enriched. STITCH and AutoDock Vina were used to predict and validate drug–gene interactions.Results: A total of 657 DEGs were screened and functional analysis emphasizes their important role in inflammatory responses and immunomodulation in CKD. Through WGCNA, the interaction network, ROC curves, and validation set, four hub genes (IL10RA, CD45, CTSS, and C1QA) were identified. Furthermore, IHC of CKD patients confirmed the results above. Immune infiltration analysis indicated that CKD had a significant increase in monocytes, M0 macrophages, and M1 macrophages but a decrease in regulatory T cells, activated dendritic cells, and so on. Moreover, four hub genes were statistically correlated with them. Further analysis exhibited that IL10RA, which obtained the highest expression level in hub genes, was involved in abnormalities in various immune cells and regulated a large number of immune system responses and inflammation-related pathways. In addition, the drug–gene interaction network contained four potential therapeutic drugs targeting IL10RA, and molecular docking might make this relationship viable.Conclusion: IL10RA and its related hub molecules might play a key role in the development of CKD and could be potential biomarkers in CKD.

IntroductionTransformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment.Patient and methodWe report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified.ResultsEGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue.ConclusionWe consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy.

Introduction: Tremendous evidence indicates that N6-methyladenosine (m6A) epigenetic modification and m6A-related enzymes constitute a complex network, which jointly regulates prevailing pathological processes and various signaling pathways in humankind. Currently, the role of the m6A-mediated molecular regulatory network in hepatocellular carcinoma (HCC) remains elusive.Methods: We recruited expression and pathological files of 368 HCC patients from The Cancer Genome Atlas cohort. Four public datasets serve as external authentication sets for nearest template prediction (NTP) validation. The correlation between 35 regulators and their prognostic value was compared. Gene set variation analysis (GSVA) was used to explore the latent mechanism. Four independent algorithms (ssGSEA, xCell, MCP-counter, and TIMER) were used to calculate the ratio of tumor cells and non-tumor cells to evaluate the tumor immune microenvironment. The m6Ascore model was established by principal component analysis (PCA). Prediction of immunotherapy and potential drugs was performed using TIDE and SubMap.Results: A total of 35 m6A regulators were widely associated, most of which were risk factors for HCC patients. The m6A phenotypic-cluster revealed differences in regulator transcriptional level, gene mutation frequency, functional pathways, and immune cell infiltration abundance under distinct m6A patterns. As expected, the m6A gene cluster confirmed the aforementioned results. The m6Ascore model further found that patients in the high-m6Ascore group were associated with lower tumor purity, higher enrichment of immune and stromal cells, upregulation of metabolic pathways, lower expression of m6A regulators, and favorable outcomes. Low-m6Ascore patients were associated with adverse outcomes. Notably, low-m6Ascore patients might be more sensitive to anti-PD-L1 therapy.Conclusion: This study found that a classification model based on the m6A manner could predict HCC prognosis and response to immunotherapy for HCC patients, which might improve prognosis and contribute to clinical individualized decision-making.

Objective To detect the main amino acid sites in the ion-conducting pore of the human α7 nicotinic acetycholine receptor(α7nAChR) by two-electrode voltage-clamp. Methods The amino acids in the transmembrane region M2 of α7 nAChR subunit (from Leu248 to Ala258) were mutated to hydrophilic serine by site-directed mutagenesis. cRNA was synthesized in vitro and injected into Xenopus oocytes. After 1～3 days, the function of wild type α7 nAChR and its mutants were detected by two-electrode voltage-clamp. Results After the hydrophilic mutation on the second transmembrane domain, it was indicated that the mutations of the hydrophobic residues (L248,V252,L255 and L256) to hydrophilic ones significantly decrease the EC50 values of the receptor to agonist acetylcholine. The hydrophilic mutations of these four M2 residues resulted in a dramatic leftward shift of the dose-response curve and decrease desensitization. Moreover, the desensitization rate was positively correlated to the EC50 values in log scale. Conclusions The residues L248, V252, L256 and L255 in the transmembrane M2 of α7 nAChR are the main sites to construct the ion-conducting pore.

Abstract It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r 2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

The 1H NMR spectra of C-2 monosubstituted norbornene and its derivatives are usually difficult to assign due to the anisotropy effect of norbornene ring and being a mixture of exo- and endo- isomers. Based on the preparation of configurationally pure C-2 substituted norbornene derivatives, this study assigned the 1H and 13C NMR signals of exo-5-norbornene-2-carboxylic acid, endo-5-norbornene-2-carboxylic acid, exo-5-norbornene-2-methanol and endo-5-norbornene-2-methanol by combined use of 1H NMR, DEPT135, 1H-1H COSY, 1H-13C HMQC and 1H-1H NOESY spectroscopy, and corresponding coupling constants. The effects of norbornene derivatives' C-2 substituents and their configurations on 1H NMR chemical shifts of the compunds were also investigated.

Accelerating mass exchange between matrix and fractures is the essence of enhanced oil recovery (EOR) in tight formations after natural depletion. Low salinity water (LSW) injection has been commercially-proven in conventional reservoirs EOR, with scale projects in progress worldwide. There is, however, a lack of understanding of the EOR effect in tight formations. Therefore, in this work, we introduced LSW-EOR to a target tight formation using huff-puff mode. Spontaneous imbibition (SI) tests were firstly performed on homogenous Berea sandstone cores with decreasing salinity brine to observe the production response. The results indicated that the oil recovery of the tight rock was boosted by tuning brine salinity. Of all the used brines with salinity ranging from 0.021% to 2.1% TDS (total dissolved salinity), the 0.21% TDS brine showed a rapid increase in oil production over imbibing time, which finally led to an incremental oil recovery of 4.5% OOIP (original oil in place). Core-scale modeling was conducted by history-matching the oil recovery dynamics of the SI results through modifying capillary pressure and relative permeability. A full-scale reservoir model was constructed using micro-seismic data to model fracture geometry combing fracturing results and scaling parameters obtained from core scale history-matching. It is proven that LSW huff-n-puff stimulated the oil production after natural depletion and improved MEE (mass exchange efficiency) of the target formation, but the EOR benefit was not comparable to CO2 and surfactant-assisted water huff-puff methods.