Spatio-temporal heterogeneity and coupling effect of mining economy, social governance and environmental conservation: Evidence from Guangxi Zhuang Autonomous Region, China.

In order to solve the problem of coordinated development among mining economy, social governance and environmental conservation in global resource-based cities, we choose Guangxi Zhuang Autonomous Region as the research area. The advantage of resource endowment and resource industry was measured by location quotient and input-output method. The panel data related to mining governance from 2010 to 2021 were selected to build the evaluation and coupling analysis model between mining economic, social governance and environmental conservation, and the spatial-temporal heterogeneity and coupling effect of them were analyzed by comprehensive empowerment evaluation, spatial autocorrelation analysis and barrier degree methods. The results show that: (1) Except for the overall upward trend of social governance, the development level of mining economy and environmental conservation are basically stable; (2) The resource-rich areas have obvious mining economic advantages, and the central cities have good social governance capabilities, and the environmental conservation effectiveness is uncertain; (3) The coupling effect between mining economy and social governance is stronger than that between mining economy and environment conservation, and the synergistic coupling effect of the three is relatively random. Finally, we put forward some policy response strategies to Guangxi, and theoretical and practical reference would be provided for resource-based cities around the world.

AGC kinases OXI1 and AGC2-2 regulate camalexin secretion and disease resistance by phosphorylating transporter PDR6.

Plant transporters regulating the distribution of secondary metabolites play critical roles in defending against pathogens, insects, and interacting with beneficial microbes. The phosphorylation of these transporters can alter their activity, stability, and intracellular protein trafficking. However, the regulatory mechanism underlying this modification remains elusive. In this study, we discovered two Orthologs of mammalian PKA, PKG, and PKC (AGC) kinases, Oxidative signal-inducible 1 (OXI1) and its closest homologue, AGC subclass 2 member 2 (AGC2-2; 75% amino acid sequence identity with OXI1), associated with the extracellular secretion of camalexin and Arabidopsis (Arabidopsis thaliana) resistance to Pseudomonas syringae and Botrytis cinerea. These kinases can undergo in vitro kinase reactions with three Pleiotropic drug resistance (PDR) transporters: PDR6, PDR8, and PDR12. Moreover, our investigation confirmed PDR6 interaction with OXI1 and AGC2-2. By performing LC-MS/MS and parallel reaction monitoring, we identified the phosphorylation sites on PDR6 targeted by these kinases. Notably, chitin induced PDR6 phosphorylation at specific residues, namely S31, S33, S827, and T832. Additional insights emerged by expressing dephosphorylated PDR6 variants in a pdr6 mutant background, revealing that the target residues S31, S33, and S827 promote PDR6 efflux activity, while T832 potentially contributes to PDR6 stability within the plasma membrane. The findings of this study elucidate partial mechanisms involved in the activity regulation of PDR-type transporters, providing valuable insights for their potential application in future plant breeding endeavors.

Dimeric eremophilane-type sesquiterpenoids from the peeled stems of Syringa pinnatifolia.

A continued phytochemical investigation guided by 1H NMR and LC-MS data on the ethanol extract from the peeled stems of Syringa pinnatifolia Hemsl. led to the isolation of 16 undescribed dimeric eremophilane sesquiterpenoids, namely syringenes R-Z (1-9) and A1-G1 (10-16). These structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, NMR, quantum-mechanics-based computational analysis of NMR chemical shifts, and single-crystal X-ray diffraction analyses, and a concise rule for determination of relative configuration of angular methyl was proposed. The results of the cardioprotective assay demonstrated that 3 exhibits a protective effect against hypoxia-induced injuries in H9c2 cells. This effect was observed at a concentration of 10 µM, with a protective rate of 28.43 ± 11.80%.

Alisol B regulates AMPK/mTOR/SREBPs via directly targeting VDAC1 to alleviate hyperlipidemia.

BACKGROUND: The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma, has been reported to ameliorate no-nalcoholic steatohepatitis (NASH) and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. PURPOSE: To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. STUDY DESIGN: HepG2, HL7702 cells, and C57BL/6J mice were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro. METHODS: Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro. Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to voltage-dependent anion channel protein-1 (VDAC1). RESULTS: ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum (ER) to golgi apparatus (GA). Further investigations indicated that the activation of AMPK by ALB was independent on classical upstream CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. CONCLUSION: Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.

9,9'-epoxylignans from Syringa pinnatifolia: A typical case of stereochemical assignment by a quantum chemical calculation with MAEΔΔδ parameter.

In the current study, twenty-two stereochemical 9,9'-epoxylignans including 19 undescribed ones were isolated from the ethanol extract of Syringa pinnatifolia in our continuing effort to understand the overall chemical spectrum of this species. These isolates were structurally elucidated by extensive spectroscopic data analysis, X-ray diffraction, modified Mosher's method, and quantum chemical calculations. Meanwhile, the utilization of 13C NMR calculation and the MAEΔΔδ parameter facilitated the stereochemical assignment of groups of lignan stereoisomers. The 13C NMR data were corrected by the averaged errors at each corresponding carbon position in groups of lignan stereoisomers, which improved the theoretic 13C NMR calculation. The finding of the stereochemical structures of 9,9'-epoxylignans is significant. It is helpful to determine the absolute configurations of molecules with the similar core. In addition, these lignans exhibited potential cardioprotective activities on H9c2 cardiomyocytes in vitro and presented significant antioxidant effect.

Effect of Traditional Chinese Non-Pharmacological Therapies on Knee Osteoarthritis: A Narrative Review of Clinical Application and Mechanism.

Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.

A Novel Thermal Tactile Sensor Based on Micro Thermoelectric Generator for Underwater Flow Direction Perception.

Underwater vehicles can operate independently in the exploitation of marine resources. However, water flow disturbance is one of the challenges underwater vehicles must face. The underwater flow direction sensing method is a feasible way to overcome the challenges but faces difficulties such as integrating the existing sensors with underwater vehicles and high-cost maintenance fees. In this research, an underwater flow direction sensing method based on the thermal tactility of the micro thermoelectric generator (MTEG) is proposed, with the theoretical model established. To verify the model, a flow direction sensing prototype is fabricated to carry out experiments under three typical working conditions. The three typical flow direction conditions are: condition No. 1, in which the flow direction is parallel to the x-axis; condition No. 2, in which the flow direction is at an angle of 45° to the x-axis; and condition No. 3, which is a variable flow direction condition based on condition No. 1 and condition No. 2. According to the experimental data, the variations and orders of the prototype output voltages under three conditions fit the theoretical model, which means the prototype can identify the flow direction of three conditions. Besides, experimental data show that in the flow velocity range of 0~5 m/s and the flow direction variation range of 0~90°, the prototype can accurately identify the flow direction in 0~2 s. The first time utilizing MTEG on underwater flow direction perception, the underwater flow direction sensing method proposed in this research is cheaper and easier to be applied on the underwater vehicles than traditional underwater flow direction sensing methods, which means it has great application prospects in underwater vehicles. Besides, the MTEG can utilize the waste heat of the underwater vehicle battery as the energy source to achieve self-powered work, which greatly enhances its practical value.

[Two new isoquinoline alkaloids from Corydalis hendersonii].

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(ß-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 µmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 µmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.

Alashanines A-C, Three Quinone-Terpenoid Alkaloids from Syringa pinnatifolia with Cytotoxic Potential by Activation of ERK.

Three quinone-terpenoid alkaloids, alashanines A-C (1-3), possessing an unprecedented 6/6/6 tricyclic conjugated backbone and quinone-quinoline-fused characteristic, were isolated from the peeled stems of Syringa pinnatifolia. Their structures were elucidated by analysis of extensive spectroscopic data and quantum chemical calculations. A hypothesis of biosynthesis pathways for 1-3 was proposed on the basis of the potential precursor iridoid and benzoquinone. Compound 1 exhibited antibacterial activities against Bacillus subtilis and cytotoxicity against HepG2 and MCF-7 human cancer cell lines. The results of the cytotoxic mechanism revealed that compound 1 induced apoptosis of HepG2 cells through activation of ERK.

[Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia].

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

Iterative double-differential direct-sequence spread spectrum reception in underwater acoustic channel with time-varying Doppler shifts.

Conventional double differential phase-shift keying modulation amplifies the phase noise and performs poorly under the time-varying direct-sequence spread-spectrum (DSSS) communication system. Therefore, the authors propose an iterative reception for DSSS communication in time-varying underwater acoustic channels. First, bit-interleaved coded modulation with iterative decoding integrated with multi-symbol differential detection is used. Second, this paper uses cross correlation method to estimate and track the Doppler shift of each symbol. Based on Doppler estimates, a dynamic linear prediction model is proposed to estimate and track the channel phase variation. Third, an algorithm for adaptive selection of reference signals is utilized to recover the magnitude attenuation of correlation peaks. Numerical simulation results demonstrate that the proposed reception achieves around 9 dB gain compared to conventional differential decision reception under constant acceleration of 0.14 m/s2. During the acoustic communication experiment in Songhua Lake, the proposed reception was tested by using a moving source at a speed of 1-6 knots at 2-m depth and the farthest distance between the transceivers is 2.8 km. The proposed reception achieves only one frame error from a total of 205 frames collected in the lake experiment, and it also achieves error-free communications over 96 frames during a 10 km depth deep-sea experiment.

A Protocol for a Single-Centered, Pragmatic, Randomized, Controlled, Parallel Trial Comparing Comprehensive Nonsurgical Therapy Options for Individuals with Lumbar Spinal Stenosis.

Aim: Lumbar spinal stenosis (LSS) is a long-term degenerative disease. Considering the risks and advantages of the patient's age range and the characteristics of the condition, non-surgical treatment is recommended. To determine the best first-line non-surgical therapy for LSS, few studies have examined different non-surgical therapies. Therefore, the main objective of this study is to determine whether the selection of comprehensive Chinese medicine (CM) treatment for LSS is more successful than non-surgical conservative treatment. Patients and Methods: In this two-armed, parallel, single-centered, pragmatic randomized controlled study, 94 LSS participants will be randomized to receive 24 sessions of comprehensive CM therapy or conservative treatment for 3 months, with follow-up assessments at 6, 9, 12, and 15 months. The primary outcome will be based on the success rate of the Zurich Claudication Questionnaire (ZCQ) for the most clinical important difference (MCID) at 3 and 15 months. Secondary outcomes include Numerical Rating Scale (NRS) scores for back and leg pain, ZCQ scores, Oswestry Disability Index scores for lumbar dysfunction, and Short-Form 12 scores for health-related quality of life at 3, 6, 9, 12, and 15 months. Adverse events and incidences of surgery will be reported anytime during the trial and follow-up. Conclusion: This protocol examines the comparative efficacy of comprehensive CM therapy compared with conventional care through a pragmatic randomized controlled trial to present data to facilitate clinical or policy decision-making. The outcomes will make it easier to decide which patient-centered treatments to prioritize for LSS.

Diverse lignans with protective effect against hypoxia/oxidative injuries to H9c2 cells from Syringa pinnatifolia Hemsl.

A bioactivity-guided fractionation on the phenolic fractions from the peeled stems of Syringa pinnatifolia Hemsl., one of representative Mongolian folk medicine in China, led to the isolation and structural determination of 11 undescribed lignans and 12 known ones. These lignans cover diverse types, among them syringanones A and B represent an unprecedented carbon skeleton (proposed syringanane) and alashanenol A possesses a rare bicyclo [3.3.1]nonadienemethanol core. Their structures were established by extensive spectroscopic data analysis, X-ray diffraction, and quantum chemical calculations. All isolates were evaluated for their cardioprotective activities on H9c2 cardiomyocytes in vitro. The results showed that five lignans exhibited the protective effects against hypoxia-induced injury at the concentrations of 1.2-40 µM and six lignans exhibited anti-oxidative stress injury at 10-40 µM. These findings account to some extend for the traditional therapeutic effects of S. pinnatifolia for the treatment of ischemic heart diseases in clinic.

High-Dimensional Data Global Sensitivity Analysis Based on Deep Soft Sensor Model.

This article investigates the sensitivity analysis (SA) of high-dimensional data to identify the effects of process variables on output quantity of interest (QoI) in industrial soft sensor modeling. The computational cost of analyzing the SA of high-dimensional data is high, and models available for SA techniques usually have limited generalization capacity. Therefore, we propose a novel high-dimensional data global SA (GSA) approach based on a deep soft sensor model to address these issues. We first develop an approximately incremental grouping (AIG) algorithm and a region-based cooperative co-evolution (RBCC) algorithm to decompose the high-dimensional data into independent regions for the GSA. Subsequently, a multihead deep soft sensor model with generalization performance is designed to determine the GSA indices of each decomposed region. Specifically, the region of interest (RoI) align algorithm provides the multihead with precisely located decomposed region features. Finally, based on the uncertainty analysis of each model head, we present a joint loss function with the Monte Carlo dropout (MC-dropout) algorithm to measure the GSA indices of each decomposed region on QoIs. Experimental evaluation results on a benchmark dataset and a real-world one demonstrate the effectiveness of the proposed approach in addressing the GSA of high-dimensional data in industrial processes.

A Novel Prognosis Signature Based on Ferroptosis-Related Gene DNA Methylation Data for Lung Squamous Cell Carcinoma.

Ferroptosis-related genes regulating an iron- and lipid reactive oxygen species (ROS)-dependent form of programmed cell death suggest critical roles for ferroptosis in cancers. However, the prognostic value of ferroptosis-related epigenetic features such as DNA methylation in lung squamous cell carcinoma (LUSC) needs to be studied. Ferroptosis-related genes are collected from the FerrDb database, and the methylation data of these related genes in LUSC methylation data downloaded from the TCGA are retrieved. The DNA methylation data (362 LUSC samples) were analyzed to screen prognostic ferroptosis-related methylation sites. After patients with complete overall survival (OS) information were randomly separated into training cohort (n = 200) and validation cohort (n = 162), the least absolute shrinkage and selection operator (LASSO) and the Cox regression were used to establish and validate the prognostic signature. The time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve analyses, Harrell's concordance index (C-index), calibration analysis, and decision curve analysis (DCA) were performed to evaluate the risk signature and related nomogram. A series of other bioinformatics approaches such as mexpress, cbioportal, maftools, string, metascape, TIMER, and Kaplan-Meier survival curve analysis were also used to determine the methylation, mutation status, protein interaction network or functional enrichment, effects on immune cell infiltration, or expression level prognosis of those signature-related genes. A total of 137 DNA methylation sites were identified as prognostic predictors corresponding to 109 ferroptosis-related genes (FRGs). The methylation signature containing 31 methylation sites proved to be superior predictive efficiency in predicting the 1-, 3-, 5-, and 10-year OS. 8 out of 28 signature-related genes were significantly related to OS time or OS state in patients with LUSC. In addition, DUSP1, ZFN36, and ALOX5 methylation status also correlated with pathological M and ALOX5 methylation correlated with pathological N. The prognostic prediction efficiency of T, N, M, and the stage was inferior to that of the DNA methylation signature. LUSC patients in the high-risk group own a significantly larger number of variants of FRGs than those in the low-risk group. In addition, negative or positive correlation patterns were presented among the different infiltrating immune cells with risk scores or signature-related genes in patients with LUSC. The expression level of 15 signature-related genes showed a significant relationship with OS of LUSC patients. A novel prognostic nomogram survival model containing 4 factors including age, pathologic T, stage, and risk group was constructed and validated, AndC-index, decision curve analysis (DCA), and calibration analysis demonstrated its excellent predictive performance. The FRG DNA methylation data-based prognostic model acts as a powerful prognostic prediction indicator in LUSC patients and is advantageous over the traditional model based on T, N, M, and stage.

Characteristics and Prognosis of Antibody Non-responders With Coronavirus Disease 2019.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading globally. Information regarding the characteristics and prognosis of antibody non-responders to COVID-19 is limited. Methods: In this retrospective, single-center study, we included all patients with confirmed COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) admitted to the Fire God Mountain hospital from February 3, 2020, to April 14, 2020. A total of 1,921 patients were divided into the antibody-negative (n = 94) and antibody-positive (n = 1,827) groups, and 1:1 propensity score matching was used to match the two groups. Results: In the antibody-negative group, 40 patients (42.6%) were men, and 49 (52.1%) were older than 65 years. Cough was the most common symptom in the antibody negative group. White blood cell counts, neutrophils, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, urea nitrogen, and creatinine were significantly higher in the antibody-negative patients than in the antibody-positive group (P < 0.005). The number of days of nucleic acid-negative conversion in the antibody-negative group was shorter than that in the antibody-positive group (P < 0.001). The hospitalization time of the antibody-negative patients was shorter than that of the antibody-positive patients (P < 0.001). Conclusion: Some COVID-19 patients without specific antibodies had mild symptoms; however, the inflammatory reaction caused by innate clinical immunity was more intense than those associated with antibodies. Non-specific immune responses played an essential role in virus clearance. There was no direct correlation between excessive inflammatory response and adverse outcomes in patients. The risk of reinfection and vaccination strategies for antibody-negative patients need to be further explored.

A Degradable and Osteogenic Mg-Based MAO-MT-PLGA Drug/Ion Delivery System for Treating an Osteoporotic Fracture.

Osteoporotic fractures are a very common bone disease that is difficult to completely cure. A large number of people worldwide suffer from pain caused by osteoporotic fractures every year, which can even cause disability and death. The compromised skeletal strength, lower density, trabecular microstructure, and bone-forming ability caused by osteoporotic fractures make them difficult to treat relative to normal fractures. An ideal scheme for osteoporotic fractures is to select internal fixation materials with matched mechanical and biological properties and carry anti-osteoporosis drugs on the plant to achieve bio-fixation and improve the condition of osteoporosis simultaneously. We designed a Mg-based MAO-MT-PLGA drug/ion delivery system (DDS) compatible with bone-like mechanical properties, degradation properties, and drug therapy. In this research, we evaluated the degradation behavior of Mg-based MAO-MT-PLGA DDS using immersion tests and electrochemical tests aided by SEM, EDS, XPS, XRD, and FT-IR. The DDS showed better corrosion resistance over Mg alloy and could release more Mg2+ due to the degradation of PLGA. According to cell viability and cell adhesion, the DDS showed better osteogenic characteristics over control group I (Mg alloy) and control group II (Mg-based MAO alloy), especially in the cells co-cultured with the leaching solution for 72 h, in which the DDS group increased to about 15% cell viability compared with group I (p < 0.05). The mRNA relative expressions, including ALP, collagen I, OCN, OPG, and Runx-2, as well as extracellular matrix calcium deposits of the DDS, are 1.5~2 times over control group I and control group II (p < 0.05), demonstrating a better ability to promote bone formation and inhibit bone resorption. After the DDS was implanted into the castrated rat model for one month, the trabeculae in the treatment group were significantly denser and stronger than those in the control group, with a difference of about 1.5 times in bone volume fraction, bone density, and the number of trabeculae, as well as the magnesium content in the bone tissue (p < 0.05). The above results demonstrated that the Mg-based MAO-MT-PLGA drug/ion delivery system is a potential treatment for osteoporotic fractures.

Syringenes A-L: Bioactive dimeric eremophilane sesquiterpenoids from Syringa pinnatifolia.

A phytochemical investigation guided by 1H NMR and LC-MS data on the ethanol extract of Syringa pinnatifolia stems led to the isolation of 11 new dimeric eremophilane sesquiterpenoids, namely, syringenes A-K (1-11) and one known analog (12, syringene L). These structures were elucidated by extensive analysis of spectroscopic data, single-crystal X-ray diffraction, and computational methods. Biological assays revealed that 1-12 exhibited different degrees of anti-inflammatory effects, and 5 and 6 showed significant cytotoxicity against human hepatoma HepG2 cells with IC50 values of 12.3 and 12.9 µM, respectively. Furthermore, flow cytometry assays and western blot analysis revealed that 5 and 6 promoted the apoptosis of HepG2 cells by activating ERK. Finally, the molecular docking analysis implied that the carbonyl and hydroxy groups at the C-11/C-6' of 5 and 6 had a good binding affinity with ERK.

A pair of enantiomeric dimers with an unprecedented skeleton from stem barks of Syringa pinnatifolia.

A pair of enantiomers with a rearranged dimeric phenylethanol skeleton, namely (±)-disyringol A (1a and 1b), were isolated from the stem barks of Syringa pinnatifolia. The structures were established using IR, UV, MS, and NMR data, and their absolute configurations were resolved by experimental and calculated ECD data analysis. Their biosynthetic pathway was speculated on the basis of a phenylethanoid precursor and was proved by a total synthesis. Compounds 1a and 1b showed the inhibition against NO production in LPS-induced RAW264.7 cells with their IC50 values of 27.28 and 24.64 µM, respectively, however no protective effect was observed against the hypoxia-induced injuries to H9c2 cells.

Hierarchical-Bayesian-Based Sparse Stochastic Configuration Networks for Construction of Prediction Intervals.

To address the architecture complexity and ill-posed problems of neural networks when dealing with high-dimensional data, this article presents a Bayesian-learning-based sparse stochastic configuration network (SCN) (BSSCN). The BSSCN inherits the basic idea of training an SCN in the Bayesian framework but replaces the common Gaussian distribution with a Laplace one as the prior distribution of the output weights of SCN. Meanwhile, a lower bound of the Laplace sparse prior distribution using a two-level hierarchical prior is adopted based on which an approximate Gaussian posterior with sparse property is obtained. It leads to the facilitation of training the BSSCN, and the analytical solution for output weights of BSSCN can be obtained. Furthermore, the hyperparameter estimation process is derived by maximizing the corresponding lower bound of the marginal likelihood function based on the expectation-maximization algorithm. In addition, considering the uncertainties caused by both noises in the real-world data and model mismatch, a bootstrap ensemble strategy using BSSCN is designed to construct the prediction intervals (PIs) of the target variables. The experimental results on three benchmark data sets and two real-world high-dimensional data sets demonstrate the effectiveness of the proposed method in terms of both prediction accuracy and quality of the constructed PIs.