A High-Strength Solid Oxide Fuel Cell Supported by an Ordered Porous Cathode Membrane.

The phase inversion tape casting has been widely used to fabricate open straight porous supports for solid oxide fuel cells (SOFCs), which can offer better gas transmission and minimize the concentration polarization. However, the overall weak strength of the macro-porous structure still limits the applications of these SOFCs. In this work, a novel SOFC supported by an ordered porous cathode membrane with a four-layer configuration containing a finger-like porous 3 mol% yttria- stabilized zirconia (3YSZ)-La0.8Sr0.2Co0.6Fe0.4O3-δ (LSCF) catalyst, porous 8 mol% yttria-stabilized zirconia (8YSZ)-LSCF catalyst, and dense 8YSZ porous 8YSZ-NiO catalyst is successfully prepared by the phase inversion tape casting, dip-coating, co-sintering, and impregnation process. The flexural strength of the open straight porous 3YSZ membrane is as high as 131.95 MPa, which meets the requirement for SOFCs. The cathode-supported single cell shows a peak power density of 540 mW cm-2 at 850 °C using H2 as the fuel. The degradation mechanism of the SOFC is investigated by the combination of microstructure characterization and distribution of relaxation times (DRT) analysis.

Temporal and Spatial Trends in HIV Positivity Rate for VCT Clinics - China, 2015-2022.

Introduction: Human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) clinics play a critical role in identifying and diagnosing HIV cases. This study aimed to describe the trend of HIV positivity rate (HPR) among Chinese VCT clinics between 2015 and 2022. Methods: This study utilized data from the China Information System for Disease Control and Prevention to analyze the trend in the HPR for VCT clinics from 2015 to 2022. The HPR was calculated by dividing the number of newly-reported HIV cases by the number of HIV tests, multiplied by 100%. To identify temporal and spatial trends in the HPR, we employed joinpoint regression analysis and the Getis-Ord hotspot analysis. Results: From 2015 to 2022, VCT clinics in China performed a total of 22,075,386 HIV tests, leading to the identification of 260,353 HIV cases, resulting in a HPR of 1.18%. The HPR consistently declined over the study period, with an average annual percent change (AAPC) of -7.5% (95% confidence interval: -12.6%, -2.2%, P<0.05). The number of HPR hotspots also decreased from 41 in 2015 to 23 in 2022. These HPR hotspots were primarily located in Yunnan, Sichuan, Guangdong, and Guangxi provincial-level administrative divisions (PLADs). Among the 31 PLADs, 16 showed a significant decrease in HPR during the study period (AAPC<0, PAAPC<0.05). Conclusions: VCT clinics in China have played a significant role in identifying HIV cases. The declining HPR observed in these clinics may indicates the progress has been made in some degree in mitigating HIV among high-risk populations. Therefore, it is crucial to further improving the utilization of VCT clinics for HIV testing.

Structure Optimization of 12ß-O-γ-Glutamyl Oleanolic Acid Derivatives Resulting in Potent FXR Antagonist/Modulator for NASH Therapy.

The farnesoid X receptor (FXR) plays a crucial role in regulating the metabolism of bile acids, lipids, and sugars. Consequently, it is implicated in the treatment of various diseases, including cholestasis, diabetes, hyperlipidemia, and cancer. The advancement of novel FXR modulators holds immense importance, especially in managing metabolic disorders. In this study, a series of oleanolic acid (OA) derivatives bearing 12ß-O-(γ-glutamyl) groups were designed and synthesized. Using a yeast one-hybrid assay, we established a preliminary structure-activity relationship (SAR) and identified the most potent compound, 10b, which selectively antagonizes FXR over other nuclear receptors. Compound 10b can differentially modulate the downstream genes of FXR, including with the upregulation of the CYP7A1 gene. In vivo testing revealed that 10b (100 mg·Kg-1) not only effectively inhibits lipid accumulation in the liver but also prevents liver fibrosis in both BDL rats and HFD mice. Molecular modeling indicated that the branched substitution of 10b extends into the H11-H12 region of FXR-LBD, possibly accounting for its CYP7A1 upregulation, which is different from a known OA 12ß-alkonate. These findings suggest that 12-glutamyl OA derivative 10b represents a promising candidate for the treatment of nonalcoholic steatohepatitis (NASH).

Discovery of 12ß-oxygenated oleanolic acid alkyl esters as potent and selective FXR modulators exhibiting hyperglycemia amelioration in vivo.

Farnesoid X receptor (FXR) ligands have been actively pursued to treat metabolic disorders, liver and bile diseases, among others. Starting from a widely occurring natural product, oleanolic acid (OA), we discovered potent and selective FXR modulator from the 12ß-oxygenated OA alkyl esters, with the assistance of molecular modeling. The representative compound 7b modulated some FXR downstream genes involved in glucose and lipid metabolism in cells, and significantly improved hyperglycemia in KKay fat mice fed with high fat diet, through the reduction of mRNA expression of gluconeogenesis genes PEPCK and G6Pase. This study provides a new series of selective FXR modulator, as well as the in vitro and in vivo evidence for their potential to improve hyperglycemia in diabetic mice through FXR antagonism.

Spatial Analysis of HIV/AIDS Cases Among Out-of-School Youth Aged 15-24 Years - China, 2010-2020.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: There are 4,000 new HIV infections every day worldwide, and 31% of which are in adolescents aged 15-24 years old. However, previous study is not aware of the distribution of out-of-school youth among this age group. WHAT IS ADDED BY THIS REPORT?: The crude reporting rate of HIV/AIDS among out-of-school youth aged 15-24 years old increased from 5.25 per 100,000 persons in 2010 to 13.75 per 100,000 persons in 2020 with a weakly aggregated spatial distribution. Local hotspots spread from southwestern China to the central, eastern, and northeastern areas. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: In the future, HIV/AIDS awareness among out-of-school youth and research on epidemic characteristics should be strengthened.

Droplet impact on cylindrical surfaces: Effects of surface wettability, initial impact velocity, and cylinder size.

HYPOTHESIS: Droplet impact on cylindrical surfaces is a widespread phenomenon observed in both nature and industrial applications. The wettability and size of the cylinders, and the initial impact velocity, are expected to influence the impact dynamics, such as generating different droplet morphology, spreading/retracting processes, and contact time, which could finally determine the anti-icing property of power transmission lines. EXPERIMENTS: A particle-based mesh-free numerical approach, many-body dissipative particle dynamics, is employed to study the impact dynamics. The cylinders with three different sizes and three types of wettability are modelled, and different initial impact velocities are set. FINDINGS: The simulations show the two liquid films (or lamellae) formed after impact can coalesce at the bottom site of a hydrophilic cylinder while they keep separate on hydrophobic and superhydrophobic cylinders. The maximum spreading diameter in the axial direction increases with the increase of impact velocity and cylinder size. Besides, the distribution of droplet detachment mode shows a strong dependence on initial impact velocity and cylinder size. In bouncing mode, the contact time increases with the increase of impact velocity while in dripping/bouncing mode, it has an opposite trend. The splashing angle is also observed to be dependent on the cylinder size.

Epidemiological Characteristics of Newly-Reported HIV Cases Among Youth Aged 15-24 Years - China, 2010-2019.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: An estimated 1,400 new cases of human immunodeficiency virus (HIV) occur every day among youths globally. However, HIV distribution among youth aged 15-24 years in China has not been researched extensively. WHAT IS ADDED BY THIS REPORT?: Between 2010 and 2019, a total of 141,557 HIV cases among the group aged 15-24 years were reported in China with a male to female ratio at 4.07∶1. The main route of HIV transmission was unprotected sex among men who have sex with men (MSM), and heterosexual transmission for females. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Effective HIV control and prevention measures need to target youth aged 15-24 years, especially among MSM. Sexual health education and HIV prevention should start from primary and secondary school levels.

A Novel Equivalent Model of Active Distribution Networks Based on LSTM.

Dynamic behaviors of distribution networks are of great importance for the power system analysis. Nowadays, due to the integration of the renewable energy generation, energy storage, plug-in electric vehicles, and distribution networks turn from passive systems to active ones. Hence, the dynamic behaviors of active distribution networks (ADNs) are much more complex than the traditional ones. The research interests how to establish an accurate model of ADNs in modern power systems are drawing a great deal of attention. In this paper, motivated by the similarities between power system differential algebraic equations and the forward calculation flows of recurrent neural networks (RNNs), a long short-term memory (LSTM) RNN-based equivalent model is proposed to accurately represent the ADNs. First, the adoption reasons of the proposed LSTM RNN-based equivalent model are explained, and its advantages are analyzed from the mathematical point of view. Then, the accuracy and generalization performance of the proposed model is evaluated using the IEEE 39-Bus New England system integrated with ADNs in the study cases. It reveals that the proposed LSTM RNN-based equivalent model has a generalization capability to capture the dynamic behaviors of ADNs with high accuracy.

Charge-Transfer Modeling and Polarization DRT Analysis of Proton Ceramics Fuel Cells Based on Mixed Conductive Electrolyte with the Modified Anode-Electrolyte Interface.

A charge-transfer model considering the mixed conductivities of proton, oxygen ion, and free electron in interface-modified La2Ce2O7 (LCO) electrolyte is designed to analyze the characteristics of proton ceramics fuel cell in the field of the open-circuit voltage, internal short-circuit current, proton-transfer number, discharging curves, oxygen/hydrogen partial pressure, and cell efficiencies. The properties of anode-supported single cells with the modified anode-electrolyte interface containing an in situ formed doped BaCeO3 reaction layer are compared to those of unmodified cells at various temperatures T and H2O partial pressures. Besides, the electrochemical impedance spectroscopies of both cells were investigated by the relaxation time distribution to distinguish different polarization processes. The results indicated that the reaction interface layer can effectively reduce the internal short-circuit current density and increase the proton-transfer number of electrolytes. Importantly, the NiO-BaZr0.1Ce0.7Y0.2O3-δ anode can also make more protons transfer from anode to cathode and participate in the cathodic reaction for LCO-based proton ceramics fuel cell. The polarization of the cell decreases with the increase of water partial pressure, which leads to the increase of open-circuit voltage and cell efficiency.

An efficient semi-synthesis of 1-hydroxyl oleanolic acid analogs.

An efficient route for the semi-synthesis of either 1α- or 1ß-OH epimers of 1-hydroxy-3-deoxyolean-12-en-28-oic acid (1), 6-8 steps from oleanolic acid is reported. The synthesis involves stereoselective formation of α,ß-unsaturated epoxy ketone and subsequent Wharton reaction as key steps, offering a new access to the 1-O-substituted oleanolic acid-type pentacyclic triterpenoids.

Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods.

The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity cluster strategy. With further docking analysis, four top-scored OA 3-O-ester derivatives were selected for synthesis. The bioassay results indicated that all four compounds 3 inhibited chenodeoxycholic acid (CDCA)-induced FXR transactivation in a concentration-dependent mode. Among them 3b and 3d are more active than the parent compound OA. A molecular simulation study was performed to attempt to explain the structure-activity relationship (SAR) and the antagonistic action. To the best of our knowledge, this is the first report on semi-synthetic pentacyclic triterpenoids with FXR-modulatory activities.

Synthesis and Biological Evaluations of Cytotoxic and Antiangiogenic Triterpenoids-Jacaranone Conjugates.

BACKGROUND: The development of antiangiogenic agents arises as a more effective and selective therapeutic approach for the treatment of cancer. In addition to reduced acute toxicity, the efficacy of chemotherapy could be improved when administered in combination specific antiangiogenic with cytotoxic agents. The conjugation or hybridization of bifunctional molecules is one of the alternative rational design strategies for co-administration of anticancer drugs. OBJECTIVE AND METHODS: The goal of this work is to prepare the conjugates of an antiangiogenic triterpene, 3-oxo oleanolic acid, and structurally related triterpenoids with a cytotoxic semibenzoquinone, jacaranone. The cytotoxic, antiproliferative and antiangiogenic activities of segments and conjugates were determined. The possible targets of conjugates 6a-6h were predicted using Similarity Ensemble Approach (SEA). RESULTS: The results showed that these conjugates are more potent in both cytotoxic and antiangiogenic assays than their corresponding parent molecules, and are also selectively more active against melanoma cells B16 and metastatic B16BL6 than the two other cancer cell lines (A549 and MCF-7) tested. The predicted antiangiogenesis related targets could involve glycogen phosphorylase, neuraminidase, interferon gamma, and tubulin beta chain. CONCLUSION: The bifunctional conjugates could be useful as dual acting antitumor/antigiogenic agents.

A novel C,D-spirodioxene taxoid synthesized through an unexpected Pd-mediated ring cyclization.

A novel C,D-spirodioxene taxoid (6) was prepared from paclitaxel (1a), with the key steps including an unexpected Pd-mediated ring cyclization. The anti-tubulin activity of 6 was decreased relative to that of 1a and a previously reported C,D-spirolactone taxane (5). These observations could be rationalized on the basis of molecular modeling results. To the best of our knowledge, this is the first example indicating that 1,4-dioxenes can be synthesized from a mono-allyl vicinal diol through a Wacker-type cyclization. This strategy may be applicable to the synthesis of other C,D-spiro taxoids.

Restoration of Microtubule Interaction and Cytotoxicity in D-seco Taxanes upon Incorporation of 20-Hydroxymethyl-4-allyloxy Groups.

To probe the exact role of the oxetane D ring in both tubulin binding and cytotoxicity of taxanes, novel D-seco taxanes bearing a C4 ether substituent have been prepared from paclitaxel 1a. Among them, 20-hydroxymethyl-4-allyloxy D-seco taxane 5e is the most active in both tubulin and cytotoxicity assays. It is only slightly less potent than 1a on tubulin polymerization promotion in vitro and the most cytotoxic among all D-seco taxanes known to date. The reason for the loss and restoration of bioactivity for these D-seco taxanes is also discussed with the assistance of NMR and molecular modeling studies. From these results, we draw a conclusion that the intact D ring of taxanes is not strictly necessary for their binding to tubulin and cytotoxic effects.

Diffusion-induced periodic transition between oscillatory modes in amplitude-modulated patterns.

We study amplitude-modulated waves, e.g., wave packets in one dimension, overtarget spirals and superspirals in two dimensions, under mixed-mode oscillatory conditions in a three-variable reaction-diffusion model. New transition zones, not seen in the homogeneous system, are found, in which periodic transitions occur between local 1(N-1) and 1(N) oscillations. Amplitude-modulated complex patterns result from periodic transition between (N - 1)-armed and N-armed waves. Spatial recurrence rates provide a useful guide to the stability of these modulated patterns.

Photophobic and phototropic movement of a self-oscillating gel.

A photosensitive self-oscillating gel that incorporates the Belousov-Zhabotinsky reaction can undergo rhythmic mechanical oscillations. We exploit the dependence of the oscillation frequency on light intensity to generate both photophobic and phototropic movement of the gel under differential illumination. Our findings may be used in designing intelligent sensors that can execute biomimetic behaviours.

[Effects of different prevention and control measures on schistosomiasis prevalence in different limnetic regions].

OBJECTIVE: To compare the schistosomiasis control effects of the comprehensive control measures based on infectious resources control and the conventional control measures, so as to provide the evidence for improving prevention and control strategies. METHODS: In the Hanbei River basin, the comprehensive control measures based on infectious resources control (conventional measures plus grazing prohibition in the marshland, machine instead of cattle, and marshland development, and so on) were carned out, and in the Nanzhi River basin, the conventional control measures were performed. The schistosomiasis epidemic data were collected, analyzed and compared from 2004 to 2011. RESULTS: In 2004, the infection rate of the populations and cattle in Nanzhi River basin was lower than that in the Hanbei River basin. From 2004 to 2011, the Oncomelania hupensis snail frame occurrence rate and the average density of living snails in the Nanzhi River basin was lower than that in the non-ploughing marshland and preventing wave woods of the Hanbei River basin, and there were schistosome infected snails in the Nanzhi River basin. From 2008 to 2010, there were no infected snails in the non-ploughing marshland of the Hanbei River basin. From 2007, the cattle have been eliminated in the Hanbei River basin. From 2007 to 2011, there were no infected snails in the preventing wave woods of the Hanbei River, but there were schistosome infected cattle found by stool examinations every year in the Nanzhi River basin. From 2004 to 2011, the infection rates of population presented downward trends in the two river basins, but the downward trend was more significant in the Hanbei River basin than in the Nanzhi River basin. CONCLUSION: The conventional control measures and comprehensive control measures based on infectious resources control are both effective, but the latter is more effective.

Isolation, identification, semi-synthesis of aziditaxel derivatives and their biological evaluation.

Two new taxoids (5 and 6) were obtained by isolating impurities in aziditaxel, and their structures were characterized based on data analysis of (1)H NMR, (13)C NMR, HPLC-MS, and through comparison with literature. In order to test their cytotoxicities against human nonsmall lung cancer cell lines (A549), sufficient amounts of compounds 5 and 6 were obtained by semi-synthesis and both of them showed equipotent cytotoxiesty compared with taxol, docetaxel, and aziditaxel.

Design and synthesis of a dual linker for solid phase synthesis of oleanolic acid derivatives.

A hydrophilic amino-terminated poly(ethylene glycol)-type dual linker for solid phase synthesis of oleanolic acid derivatives using trityl chloride resin was designed and synthesized for the first time. Model reactions in both liquid and solid phase were performed to show the feasibility of its selective cleavage at two different sites. The biological assay results indicated that the long and flexible alkyl ether functionality in the linker is less likely to be critical for the binding event. Following the successful solid-phase synthesis of model compounds, the potential of this dual linker in reaction monitoring and target identification is deemed worthy of further study.

Pentacyclic triterpenoids and their saponins with apoptosis-inducing activity.

Pentacyclic triterpenoids exert their antitumor activity through different mechanisms, one of which is apoptosis induction. Although there are many reports on the apoptosis inducing activity of pentacyclic triterpenoids, a systematic survey and discussion on their structure-activity relationships (SARs) is still lacking. In this review, we summarized such activity of oleanane, ursane and lupane type triterpenoids, the most abundant pentacyclic triterpene prototypes in plants. Their structural characteristics responsible for the activity are also discussed, in order to unravel their SARs for the apoptotic induction and benefit further investigations on the antitumor triterpenoids.