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A phytochemical investigation of an East China Sea collection of the brown alga Dictyota coriaceahas led to the isolation of four novel nitrogen-containing crenulide diterpenoids, named coriaceumins A–D (1–4), two rare nitrogenous xenicane diterpenoids, dictyolactams C (5) and D (6), and one known crenulide diterpenoid, hydroxycrenulide (7). The structures of the new compounds were elucidated by detailed spectroscopic data analyses, including HRESIMS and 1D/2D NMR. The absolute configurations were determined by a comparison of the experimental ECD spectra with the spectra computed by DFT-based quantum chemical calculations. Coriaceumins A–D (1–4) represent the first examples of nitrogen-containing crenulide diterpenoids. In a bioassay, compounds 2, 3, 5, and 7were found to exhibit different levels of inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) with IC50values ranging from 7.3 to 19 μM. In addition, the primary structure–activity relationships of all the isolates were summarized.

Although enrofloxacin (ENR) is a widely used broad-spectrum antibiotic in veterinary medicine, its residues in animals can pose a risk to human health. Thus, we developed a new method for detecting ENR based on aptamers and AuNPs. In the absence of ENR, the aptamers attached to the surface of the AuNPs viaelectrostatic interactions to protect the AuNPs from NaCl, and the solution remained red. Conversely, the aptamer bonded with ENR, leading the aptamer to detach from the AuNP surface, and the color of the solution changed from red to blue. Based on this principle, ENR can be qualitatively detected by the naked eye and quantitatively detected by measuring the absorbance ratio at 650 nm and 530 nm. The experimental results showed a good linear relationship within the ENR concentration range of 0–400 nM, with a limit of detection (LOD) of 1.72 nM, which is satisfactory for detection in food safety. Additionally, this method has also been successfully applied to the detection of ENR in tap water, river water, milk, serum and urine, with good recovery rates and RSD values of less than 7%, indicating its great potential for ENR detection in environmental water samples. More importantly, the combination of this method with a smartphone platform provided great convenience for on-site and visual detection of ENR, offering promising applicability prospects.

We designed and prepared probe W-1for the detection of H2O2. W-1showed excellent selectivity for H2O2and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2concentration (0–100 μM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2in cells to distinguish normal cells and cancer cells. Lastly, W-1was used for monitoring the H2O2fluctuation of the diabetic process in mice, and the results showed an increase in H2O2levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1), along with its two new derivatives, lyonensinols B and C (2 and 3), and six known triterpenoids (4 – 9). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2 (OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2) and C (3) represent the first examples of norursane-type triterpenoids acylated with a p -coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7 , and 8 at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7 , and 8 exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3 and 8 , bearing a C-3 trans - p -coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2 and 7) with a cis - p -coumaroyl group. [ABSTRACT FROM AUTHOR]

In order to effectively solve the tripping rollover problem caused by heavy dump trucks on concave-convex roads, an integrated control method combining differential braking control and active suspension control is proposed. A nine-degree-of-freedom dynamic model for heavy dump trucks is established, and the lateral load transfer rate is used as the rollover evaluation index. The braking torque is provided for the four wheels by the method of differential braking control, and the active suspension control force is provided for the active suspension by the method of active suspension control to improve the roll stability and smoothness of the dump truck. The co-simulation of MATLAB/Simulink and Trucksim is carried out under the fishhook tripping condition and J-turn tripping condition. The simulation results show that, compared with active suspension control and differential braking control, the integrated control method proposed in this paper reduces the peak body roll angle by additional 4.505 deg and 0.182 deg under the fishhook tripping condition, and reduces the peak body roll angle by additional 2.21 deg and 0.077 deg under the J-turn tripping condition, which shows better rollover resistance. And the integrated control method reduces the pitch angular acceleration of the vehicle by additional 2.53 deg/s2and 0.32 deg/s2under the fishhook tripping condition, reduces the pitch angular acceleration of the vehicle by additional 0.73 deg/s2and 0.30 deg/s2under the J-turn tripping condition, which shows better ride comfort.

Heavy-duty dump trucks easily roll over under extreme steering conditions. To solve this problem, this paper proposes an anti-rollover controller to improve the driving stability of heavy-duty dump trucks. A nine-degree- freedom dynamic model of heavy-duty dump trucks was established. Considering the output constraint characteristics of the active suspension actuator, an active suspension control method based on distributed model predictive control (DMPC) is given. In this method, the high-dimensional vehicle system is split into multiple low-dimensional suspension control subsystems, and a separate model predictive controller for each subsystem is designed. With the improved lateral load-transfer rate (LTR) as the rollover evaluation index, additional active suspension force is provided for the vehicle through active suspension control to improve driving stability. With the co-simulation of MATLAB/Simulink and Trucksim, the simulation verification is carried out under fishhook and J-turn conditions. The results show that the designed anti-rollover control method based on DMPC can effectively inhibit the vehicle rollover.

The pelvic floor muscle (PFM) is a critical structure maintaining the support system of pelvic organs, primarily composed of the anal support belt. Structural abnormalities and functional disorders may lead to clinical pathological changes, resulting in pelvic floor dysfunction (PFD), significantly impacting patient health. To address the challenges in PFD treatment, we first constructed a novel Zn4L2(phen)4for drug delivery and characterized its structure and fluorescence properties. Subsequently, we developed a stable and biocompatible drug, MOFs@SiO2nanoparticles, loaded with Oxybutynin. Detailed characterization of their structure was performed. An in vitro cellular model of PFD was established through mechanical injury, and our synthesized novel Zn4L2(phen)4@SiO2-Oxybutynin particles successfully alleviated the induced upregulation of MDA and downregulation of GPX4 associated with PFD, demonstrating the particle's efficacy in treating PFD by regulating ferroptosis. This study highlights the significant potential of this novel preparation strategy in the biomedical field.

To explore the effect of amyloid-β peptide (Aβ) on mandibular condyle to develop a new treatment for postmenopausal women with Temporomandibular joint osteoarthritis.

Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teffcells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3β1integrin and undergo in situtransformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teffcells via the activatable α4β1integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivostructural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.

Mining is among the human activities with widest environmental impacts, and mining-impacted environments are characterized by high levels of metals that can co-select for antibiotic resistance genes (ARGs) in microorganisms. However, ARGs in mining-impacted environments are still poorly understood. Here, we conducted a comprehensive study of ARGs in such environments worldwide, taking advantage of 272 metagenomes generated from a global-scale data collection and two national sampling efforts in China. The average total abundance of the ARGs in globally distributed studied mine sites was 1572 times per gigabase, being rivaling that of urban sewage but much higher than that of freshwater sediments. Multidrug resistance genes accounted for 40% of the total ARG abundance, tended to co-occur with multimetal resistance genes, and were highly mobile (e.g. on average 16% occurring on plasmids). Among the 1848 high-quality metagenome-assembled genomes (MAGs), 85% carried at least one multidrug resistance gene plus one multimetal resistance gene. These high-quality ARG-carrying MAGs considerably expanded the phylogenetic diversity of ARG hosts, providing the first representatives of ARG-carrying MAGs for the Archaea domain and three bacterial phyla. Moreover, 54 high-quality ARG-carrying MAGs were identified as potential pathogens. Our findings suggest that mining-impacted environments worldwide are underexplored hotspots of multidrug resistance genes.

Adoptive cellular therapies are making major strides in the treatment of cancer, both for hematologic and solid tumors. These cellular products include chimeric antigen receptor T cells and T-cell receptor–modified T cells, tumor-infiltrating lymphocytes, marrow-infiltrating T cells, natural killer cells as well as macrophage-based therapeutics. Advancement in genomics, computational biology, immunology, and cell therapy manufacturing has facilitated advancement of adoptive T cell therapies into the clinic, whereas clinical efficacy has driven Food and Drug Administration approvals. The growth of adoptive cellular therapy has, in turn, led to innovation in the preclinical models available, from ex vivocell-based models to in vivoxenograft models of treatment. This review focuses on the development and application of in vitromodels and in vivomodels (cell line xenograft, humanized mice, and patient-derived xenograft models) that directly evaluate these human cellular products.

‘CandidatusLiberibacter asiaticus (CLas)’, which causes citrus Huanglongbing (HLB) disease, has not been successfully cultured in vitroto date. Here, a rapid multiplication system for CLas was established through in vitroregeneration of axillary buds from CLas-infected ‘Changyecheng’ sweet orange (Citrus sinensisOsbeck). Stem segments with a single axillary bud were cultured in vitroto allow CLas to multiply in the regenerating axillary buds. A high CLas titer was detected in the regenerated shoots on an optimized medium at 30 days after germination (DAG). This titer was 28.2-fold higher than in the midribs from CLas-infected trees growing in the greenhouse. To minimize contamination during in vitroregeneration, CLas-infected axillary buds were micrografted onto seedlings of ‘Changyecheng’ sweet orange and cultured in a liquid medium. In this culture, the titers of CLas in regenerated shoots rapidly increased from 7.5×104to 1.4×108cells μg–1of citrus DNA during the first 40 DAG. The percentages of shoots with >1×108CLas cells μg–1DNA were 30 and 40% at 30 and 40 DAG, respectively. Direct tissue blot immunoassay (DTBIA) indicated that the distribution of CLas was much more uniform in regenerated plantlets than in CLas-infected trees growing in the greenhouse. The disease symptoms in the plantlets were die-back, stunted growth, leaf necrosis/yellowing, and defoliation. The death rate of the plantlets was 82.0% at 60 DAG. Our results show that CLas can effectively multiply in citrus plantlests in vitro. This method will be useful for studying plant-HLB interactions and for rapid screening of therapeutic compounds against CLas in citrus.

In response to the characteristics of nonlinearity, high coupling, and uncertainty in model parameters in the underactuated overhead crane lifting system model, and considering the problem of existing control methods relying on the model and full state information feedback, this paper designs an overhead crane lifting system control strategy based on RBF network dynamic sliding mode robustness control. This control strategy is founded on the sliding mode control concept as the structural framework, with the design of the sliding mode surface accounting for the influence of control output changes. By setting fuzzy rules, the sliding mode switching term is adaptively made, and the adaptive rule of the RBF neural network is further derived to fit the complex and unknown dynamic part of the overhead crane system. The closed-loop system error of this control strategy is proven to satisfy the asymptotic stable convergence condition through Lyapunov theory and Barbalat’s lemma theory. In a demonstration of effectiveness, the control strategy is compared with the Hierarchical Sliding Mode Control, The experimental results prove control strategy designed in this paper showing enhanced stability, absence of long-term high-frequency jitter, excellent anti-swing control effect on the load, and strong robustness. Moreover, under a certain degree of system parameter changes, the control strategy maintains stability. Notably, the system ensures stable tracking and positioning of the trolley, achieving zero overshoot.

Continued interest in bioactive alkaloids led to the isolation of two undescribed alkaloids, ophiorrhines F (1) and G (2), from the aerial parts of Ophiorrhiza japonica.Their structures were elucidated based on spectroscopic methods, electronic circular dichroism, and calculated NMR with DP4+ analysis. These two alkaloids represent key biological genetic intermediates in the formation of ring C in the ophiorrhines. Compound 1exhibited good inhibition on LPS-induced B cell proliferation with an IC50value of 0.38 μM and showed significant selective inhibitory activity on a B cell proliferation response with a selective index of 548.42. A preliminary study indicated that 1may have a new mechanism of immunosuppression.

Two novel rearranged Diels–Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A–D (3–6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7and 8) and two 2-arylbenzofurans (9and 10). Morunigrines A (1) and B (2) are a novel class of Diels–Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone–stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1and 2is also proposed. Compounds 1and 2exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50values of 1.8 ± 0.2 and 1.3 ± 0.3 μM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 μM).

Byline: Nurul. Abu Bakar, Ai-Hong. Chen Context: Children with learning disabilities might have difficulties to communicate effectively and give reliable responses as required in various visual function testing procedures. Aims: [...]

Graphic Abstract:

Seven new merosesquiterpenoids, trichothecrotocins D–J (1–7), two new trichothecene sesquiterpenoids, trichothecrotocins K (12) and L (13), and six known compounds (8–11, 14, and 15), were isolated from a potato-associated fungus, Trichothecium crotocinigenum. Compounds 5and 6were racemates which were further separated as pure enantiomers. Structures together with absolute configurations were established by extensive spectroscopic analysis, as well as quantum chemistry calculations on ECD and optical rotations. Compounds 1–4are rare meroterpenoids featuring a seco-phenyl group, while 1and 2possessed a novel 6–6/5 fused ring system. Compounds 1–4, 8, 11, and 12showed antifungal activity against four plant pathogens with MIC values of 8–128 μg/mL. It is suggested that the meroterpenoids produced by T. crotocinigenummay play an important role in the antifungal property of the fungus, thereby protecting the host plant, i.e., potato.

Considering the geological hazards attributed to the highway slope, using a common simple model cannot accurately assess the stability of the slope. First, principal component analysis (PCA) was conducted to extract the principal components of six factors (namely, bulk density, cohesion, internal friction angle, slope angle, slope height, and pore water pressure ratio) affecting the slope stability. Second, four principal components were adopted as input variables of the support vector machine (SVM) model optimized by genetic algorithm (GA). The output variable was slope stability. Lastly, the assessing model of highway slope stability based on PCA-GA-SVM is established. The maximal absolute error of the model is 0.0921 and the maximal relative error is 9.21% by comparing the assessment value and the practical value of the test sample. The above studies are conducive to enrich the assessing model of highway slope stability and provide some reference for highway slope engineering treatment.

Objective: To observe the effects of electroacupuncture (EA) on the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex of type 2 diabetic rats with cognitive impairment (CI), and to explore the mechanism of EA in improving the learning and memory abilities. Methods: A total of 100 Sprague-Dawley (SD) rats were divided into a normal group (n=10) and a model group (n=90) by random number table method. Rats in the model group were intraperitoneally injected with a small dose of streptozotocin (STZ) to establish the type 2 diabetic models, after being fed with high-fat and high-sugar diet for 1 month. Twenty CI rats were selected from the 50 successful model rats by the Morris water maze (MWM) test and randomly divided into a model group and an EA group according to the blood glucose level and MWM data (n=10). Rats in the EA group received acupuncture at Zusanli (ST 36), Neiting (ST 44) and Yishu (Extra), of which Zusanli (ST 36) and Neiting (ST 44) were stimulated by EA apparatus, 20 min/time, once a day for 6 d a week and 4 consecutive weeks. The rats in the model and the normal groups were fixed without treatment. After 4-week treatment, the random blood glucose level of the rats was measured; the learning and memory abilities of rats were measured by MWM; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells; Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex. Results: After modeling, the random blood glucose level and the escape latency tested by MWM were significantly increased, and the number of crossing the platform tested by the MWM was decreased in the EA and model groups, and were significantly different from those in the normal group (P<0.05 or P<0.01), while the differences between the model group and the EA group were not statistically significant (all P>0.05). After 4-week treatment, the random glucose level and the escape latency tested by MWM were significantly increased (both P<0.05), and the number of crossing the original platform tested by the MWM was significantly reduced (P<0.01), the protein and gene expressions of Bax and Caspase-3 were significantly increased (all P<0.001), the protein and gene expressions of Bcl-2 were significantly reduced (both P<0.001), and the number of neuron apoptosis was significantly increased (P<0.001) in the model group than in the normal group; the random blood glucose level was significantly reduced (P<0.05), the escape latency tested by MWM was significantly shortened (P<0.05), and the number of crossing the original platform tested by MWM was significantly increased (P<0.05), the protein and gene expressions of Bax and Caspase-3 were significantly reduced (all P<0.001), the protein and gene expressions of Bcl-2 were significantly increased (both P<0.001), and the number of neuron apoptosis was significantly reduced (P<0.001) in the EA group than in the model group. Conclusion: EA can improve the learning and memory damages induced by type 2 diabetic model rats with CI; the action mechanism may be achieved via anti-apoptosis.

Two new p-terphenyls, strepantibins A and B (1and 2), along with the first representative of a naturally occurring bisphenyltropone, strepantibin C (3), were characterized from a Streptomycessp. associated with the larvae of the mud dauber wasp Sceliphron madraspatanum. Their structures were determined by high-resolution electrospray ionization mass spectrometry, NMR, and X-ray crystallography data interpretation. Strepantibins A–C inhibited hexokinase II (HK2) activity and displayed antiproliferative activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5. In SMMC-7721 cells treated with strepantibin A, the morphological characteristics of apoptosis were observed.

The goal of this study is to explore effective treatments for peripheral facial paralysis and to evaluate the clinical efficacies of warm needling therapy and acupuncture in peripheral facial paralysis.

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl–acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels–Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom–transfer hydrogenation and subsequent Cu-catalyzed carbenoid C–H insertion afford platensilin. Furthermore, the intramolecular Diels–Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47exhibits improved antibacterial activity (MIC80= 0.0625 μg/mL) against S. aureuscompared to platensimycin.

Graphical Abstract:

Byline: Ai-Hong. Chen, Fatin. Norazman, Noor. Buari Background: Visual acuity is an essential estimate to assess ability of the visual system and is used as an indicator of ocular health [...]

A cytochalasan, xylarichalasin A, was obtained from the endophytic fungus Xylariacf. curtaharbored in Solanum tuberosum. Its structure was elucidated by comprehensive spectroscopic methods including HRESIMS, 1D/2D NMR, and residual dipolar coupling analysis as well as quantum chemistry calculations including DFT GIAO 13C NMR and ECD calculation. It has an unprecedented 6/7/5/6/6/6 fused polycyclic structure. In bioassay, xylarichalasin A showed cytotoxicity against human cancer cell lines with IC50value ranging from 6.3–17.3 μM.

Reactive metabolites (RMs) generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI). Like many synthetic drugs undergoing metabolic activation to form RMs which are often associated with drug toxicity, it is recognized that some herbal components may be also converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYP450s). This review focuses on the metabolic activation of herbal components and its liver toxicological implications. By summarizing references, we found that hepatotoxic herbal components via producing RMs have some certain structural dependence. There is a correlation between the generation of RMs and the structures, which provides a good chance for the early discovery of toxic ingredients in Traditional Chinese medicines (TCMs): i) A potential hepatotoxic component information database based on active functional groups can be built, which might provide an early information for the basic research of hepatotoxic substances in TCMs; ii) RMs can combine with CYP450s to form a complete antigen, which eventually leads to an antigen-specific immune response. RMs-CYP450 protein complete antigen can be set up, and the potential idiosyncratic liver toxicity might be predicted by testing RMs-CYP450 protein antibody in plasma.

Curtachalasins C–E (1–3), which have an unprecedent bridged 6/6/6/6 ring system, were identified from the endophytic fungus Xylariacf. curta. Residual dipolar coupling analyses associating with density functional theory calculations were utilized to determine the relative configuration of noncrystallizable compound 2. The absolute configurations of 1–3were determined by X-ray diffraction and electronic circular dichroism calculations. Remarkably, curtachalasin C (1) showed significant resistance reversal activity against fluconazole-resistant Candida albicans.

ObjectiveWe aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images.DesignA prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2).ResultsAUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied.ConclusionDLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients.Trial registration numberNCT02313649; Post-results.

This study is a case–control study to explore risk and protective factors, including clinical data and bone mineral density (BMD), affecting vertebral body fragility fracture in elderly men and postmenopausal women. In addition, we investigate the effectiveness of lumbar spine BMD by quantitative computed tomography (QCT) in discriminating vertebral fragility fracture.

Two unique cytochalasans, curtachalasins A (1) and B (2), were purified from the endophytic fungus Xylaria curtaE10 harbored in the plant Solanum tuberosum. Their structures were determined by extensive spectroscopic methods, X-ray crystallographic analysis, and electronic circular dichroism calculations. These two compounds feature an unprecedented pyrolidine/perhydroanthracene (5/6/6/6 tetracyclic skeleton) fused ring system.

Two trichothecene sesquiterpenoids, trichothecrotocins A (1) and B (2), and a merosesquiterpenoid racemate, (±)-trichothecrotocin C (3), were obtained from potato endophytic fungus Trichothecium crotocinigenumby bioguided isolation. Their structures were elucidated by extensive spectroscopic methods, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compounds 1and 2are trichothecenes possessing new ring systems. Compound 3possesses a novel 6/6–5/5/5 fused ring system. Compounds 1–3showed antiphytopathogenic activities with MIC values of 8–128 μg/mL.

We applied KF Particle, a Kalman Filter package for secondary vertex finding and fitting, to strange and open charm hadron reconstruction in heavy-ion collisions in the STAR experiment. Compared to the conventional helix swimming method used in STAR, the KF Particle method considerably improved the reconstructed Λ, Ω, and D0significance. In addition, the Monte Carlo simulation with STAR detector responses could adequately reproduce the topological variable distributions reconstructed in real data using the KF Particle method, thereby retaining substantial control of the reconstruction efficiency uncertainties for strange and open charm hadron measurements in heavy-ion collisions.

Background: Deficiency of DNA mismatch repair is a common feature of cancers exhibiting instability of microsatellite DNA sequences. Cancers with microsatellite instability are recognizable by their high rate of spontaneous frameshift mutations within microsatellite sequences, their resistance to killing by cytotoxic agents, and their localization to specific tissues, e.g., the proximal colon and stomach. We hypothesized that the mismatch repair deficiency of these cancers would make them vulnerable to environmental or chemical frameshift-inducing agents. This study was undertaken to test whether exogenous frameshift-inducing agents selectively induce mutations in mismatch repair-deficient cells of mutagen-exposed tissues like the colon and whether cytotoxic doses of these agents would preferentially kill those cells. Methods: Cytotoxicity of the acridine mutagen 6-chloro-9-[3-(2-chloroethylamino) propylamino]-2-methoxyacridine (ICR191), a DNA frameshift inducer, was determined in the mismatch repair-deficient human colon carcinoma cell line HCT116 versus the repair-reconstituted derivative HCT116+C3. Vulnerability to the mutagenic effects of ICR191 was determined by transfection of HCT116 or HCT116+C3 cells with a frameshift reporter vector, followed by treatment of the cells with ICR191. Alternatively, the reporter vector was reacted ex vivo with ICR191, and the derivatized vector was then transfected into HCT116 or HCT116+C3 cells. Results: ICR191 proved to be fivefold to 10-fold more potent in inducing mutations in mismatch repair-deficient HCT116 cells than in mismatch repair-proficient HCT116+C3 cells. Moreover, at cytotoxic doses of ICR191, repair-deficient HCT116 cells proved to be fivefold more vulnerable to killing than did HCT116+C3 cells. Conclusions: Frameshift-inducing mutagens can selectively induce mutations in mismatch repair-deficient cells versus mismatch repair-proficient cells. Environmental exposures may, therefore, favor development of cancers with microsatellite instability in tissues like the gut. Frameshift-inducing agents can, however, also preferentially kill mismatch repair-deficient cancer cells and, thus, may be promising as model therapeutic compounds. [J Natl Cancer Inst 2000; 92:480-5]

This prospective multicenter study confirmed that the performance of two-dimensional shear-wave elastography is superior to other noninvasive methods for noninvasive assessment of cirrhosis.

Theileria luwenshuniand Theileria uilenbergiare important tick-borne pathogens and cause substantial losses to the sheep industry in China. The improvement in detection techniques has allowed the identification of multi-homing parasitism in Theileriaparasites. Herein we evaluated the experimental infectivity of T. luwenshuniand T. uilenbergiin Chinese Kunming mice by screening blood samples of experimentally inoculated mice by microscopic examination (ME) and PCR. T. luwenshuniinfected Chinese Kunming mice and 20 mice inoculated with this parasite were positive by ME and PCR. In addition, T. uilenbergiinfected mice and 20 mice inoculated with this species were positive by ME and PCR. However, the number of red blood cells and the levels of hemoglobin of 40 infected mice had no obvious changes in the course of infection. Our results demonstrated the multi-homing parasitism of T. luwenshuniand T. uilenbergi,which were believed to be parasites of sheep and goats. This study was the first to demonstrate the infection of T. luwenshuniand T. uilenbergiin Kunming mice.

To investigate the chemical constituents from the roots of Angelica dahurica.

AbstractA smart home module program is designed based on Linux, in the ARM11 embedded development environment, and by using the UP-Magic 6410 development board. A touch-screen graphical interface for human-computer interaction is designed using QT. The sensor module is integrated into the underlying QT program, and the actuator module program performs external calls via QT, thus a complete set of smart home terminal is constituted. The function of remote video monitoring and the function of displaying module statuses on webpage are realized through connecting video cameras to the development board as well as constructing GoAhead web server and Spcaserv video server. A face recognition program is designed using MATLAB, a database for storing the face information for different users is designed, and they are connected to the smart home terminal. Based on face recognition, the identity information for the current user and the desired temperature are displayed, and the speed of the DC motor is changed. This system can also realize sound and light alarm. Alarm for harmful gas can be raised under the help of smoke sensor. The photosensitive sound switch module is used for simulating the voice control device so as to facilitate the user’s control of the DC motor switch. Infrared irradiation sensor is used for simulating the identity-card identification equipment, so as to limit the system users. Through the coordination of the above parts, a complete smart home system which is composed of a computer, embedded development environment, sensors, actuators and ancillary devices is finally established.

The evolution of the helium-related defect in polycrystalline tungsten was studied by Doppler Broadening Positron Annihilation Spectroscopy and Scanning Electron Microscope as functions of annealing temperature and implantation fluence. The experimental results showed that the defect type was not changed at lower annealing temperature, and the decline of S parameter manifested that the lower temperature annealing led the decrease of defect concentration. In addition there existed the same defect type with the increment of the implantation fluence, thus the rise of S parameter implied the increase of the defect concentration.

The microstructure of He+-irradiation induced defects in tungsten was studied as functions of annealing temperature by means of scanning electron microscope (SEM) and Doppler broadening positron annihilation spectroscopy (DB-PAS). The results show that the S parameter become higher after helium implanted in tungsten. When the annealing temperature increases to 923 K, plenty of large size of holes and new types of defects could be found in this sample.

W/Cu multilayer nanofilms and pure W nanofilms were prepared in pure Ar and He/Ar mixing atmosphere by radio frequency magnetron sputtering method. The defect evolution of the samples was characterized by Doppler broadening positron annihilation spectroscopy (DB-PAS).The results show that plenty of defects can be produced by introducing helium (He) into W/Cu multilayer nanofilms. With the natural storage time increasing, the helium located in the near surface of W/Cu multilayer nanofilm would be released gradually and induce the coalescence of the helium related defects due to the diffusion of the helium and defects. In addition, the pure W nanofilms were irradiated by 30 keV helium ions and 40 keV hydrogen (H) ions in sequence at room temperature. From the DB-PAS analysis, it can be shown that a large number of vacancy-type defects are produced due to the He and/or H irradiation. H ions would be trapped by He related defects and produced He-H-V complexes.

Two new seco-sativene sesquiterpenoids, bipolenins D (1) and E (2), a new seco-longifolene sesquiterpenoid, bipolenin F (3), together with three known analogues (4–6), were obtained from cultures of endophytic fungus Bipolaris eleusines. Their structures were established by MS and NMR data. Compounds 1–6showed no activity to five human cancer cell lines.

Replacement therapy with factor VIII (FVIII) is used in patients with hemophilia A for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, because of a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard immune tolerance induction (ITI), is an unmet goal. We previously generated engineered antigen-specific regulatory T cells (Tregs), created by transduction of a recombinant T-cell receptor (TCR) isolated from a hemophilia A subject's T-cell clone. The resulting engineered T cells suppressed both T- and B-cell effector responses to FVIII. In this study, we have engineered an FVIII-specific chimeric antigen receptor (ANS8 CAR) using a FVIII-specific scFv derived from a synthetic phage display library. Transduced ANS8 CAR T cells specific for the A2 domain proliferated in response to FVIII and ANS8 CAR Tregs were able to suppress the proliferation of FVIII-specific T-effector cells with specificity for a different FVIII domain in vitro. These data suggest that engineered cells are able to promote bystander suppression. Importantly, ANS8 CAR-transduced Tregs also were able to suppress the recall antibody response of murine splenocytes from FVIII knockout mice to FVIII in vitro and in vivo. In conclusion, CAR-transduced Tregs are a promising approach for future tolerogenic treatment of hemophilia A patients with inhibitors.

The zero degree calorimeter (ZDC) at RHIC-STAR was installed in the year 2000. After running for more than 10 years, the performance of the STAR-ZDC cannot maintain a proper status because of the radiation damage. The ZDC on RHIC-BRAHMS had been moved to STAR in 2011 after some tests. We present here the result of the tests as well as the physical performance of those ZDC modules between the 2011 and 2015 RHIC runs. The excellent energy resolution of the ZDC in heavy ion collision provides a good candidate for future detector development, such as the CSR experiment at CAS-Lanzhou facility.

Two monoterpenoid indole alkaloids, ophiorrhines A (1) and B (2), were obtained from plant Ophiorrhiza japonicaBI. Their structures were elucidated by extensive spectroscopic methods and single crystal X-ray diffraction. Compounds 1and 2possess a novel spirocyclic ring system. Its biosynthesis pathway is proposed. Compound 2exhibits potent inhibitory activity against concanavalin A (Con A) induced T cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation with IC50values 13.3 and 7.5 μM, respectively. Compound 1exhibits significant inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with IC50value 18.6 μM.

Antroalbocin A (1), a sesquiterpenoid possessing a bridged tricyclic system, was isolated from cultures of the higher fungus Antrodiella albocinnamomea(Basidiomycota). The structure with the absolute configuration was determined by extensive spectroscopic methods and single-crystal X-ray diffraction. A plausible biosynthetic pathway for 1was proposed. Compound 1was found to inhibit Staphylococcus aureuswith an MIC value of 169 μM.

Four undescribed cytochalasins (1–4) were isolated from the endophytic fungus Boeremia exigua. Structurally, boerelasin A (1) represents the first example of a cytochalasin with a rare 5/5 bicyclic carbon core. Boerelasin B (2) possesses an unprecedented 5/6/5/6/8 pentacyclic ring system. Boerelasin C (3), a derivative from the common biosynthetic intermediate to 1, is a macrocyclic ring-opening cytochalasin, and boerelasin D (4) contains an uncommon six-carbon alkyl acid side chain. The structures were elucidated based on spectroscopic methods, electronic circular dichroism, spin–spin coupling constants, and calculated nuclear magnetic resonance with DP4+ analysis. These compounds exhibited significant cytotoxicity against the tumor cells.

Graphical Abstract:

Several bulk metallic glasses (BMGs) were selected to in vitro assess their magnetic resonance imaging (MRI) compatibility with agarose gel as a phantom, in terms of the extent of susceptibility artifacts in magnetic resonance image. The investigated metals include the Au 49 Ag 5.5 Pd 2.3 Cu 26.9 Si 16.3 , Zr 61 Ti 2 Cu 25 Al 12 , Cu 50.4 Ni 5.6 Ti 31 Zr 13 and Ti 47 Cu 38 Zr 7.5 Fe 2.5 Sn 2 Si 1 Ag 2 , together with pure titanium (CP-Ti) and Co–28Cr–6Mo alloy (ASTM-F799) for comparison. The artifact extent in MR images was quantitatively characterized according to the total volume in reconstructed 3D images with a series of slices under acquisition by fast spin echo (FSE) sequence and gradient echo (GRE) sequence. As indicated, artifact severity of the BMGs is much less than that of the CoCrMo alloy. The AuAgPdCuSi BMG manifested the smallest artifact among the four BMGs, while the TiCuZrFeSnSiAg BMG is comparative to the CP-Ti. The MRI compatibility of BMGs is ranked as a sequence of the Au-, Zr-, Cu- and Ti-based alloys. Dependence of material magnetic susceptibility on artifact extent is also the case of the BMGs, even though it does not follow a simple linear relationship within a range of Δ χ v  = 30–180 ppm. These findings are of interest to reveal that the BMGs are potentially applied in the fields associated with an interventional MRI for MRI-guided surgeries. [ABSTRACT FROM AUTHOR]