Research progress of autophagy in heart failure.

Heart failure poses a significant threat to global public health within the realm of cardiovascular diseases. Its pathological progression involves various alterations in cardiomyocytes, among which autophagy, a crucial intracellular degradation mechanism, plays a pivotal role. Autophagy facilitates the breakdown of damaged organelles and proteins, thereby maintaining cellular homeostasis. In the context of heart failure, autophagy coexists with apoptosis and necrosis, influencing myocardial hypertrophy and ventricular remodeling. However, its impact on heart failure manifests a dual nature: moderate autophagy aids in cardiac repair, whereas excessive autophagy may exacerbate ventricular remodeling and cell demise. This review delves into the fundamental biology of autophagy, elucidating its involvement in the pathological cascade of heart failure and its correlation with cardiac hypertrophy and ventricular remodeling. Furthermore, an analysis of the interplay between autophagy regulatory factors and heart failure sheds light on the potential therapeutic implications of autophagy in the prevention and management of heart failure. This exploration provides a theoretical foundation for novel treatment strategies in combating heart failure.

Effect of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on expression of TRPV1 and CGRP in the myocardial tissue of chronic heart failure rats. / 艾灸"心俞""肺俞"å¯¹æ ¢æ€§å¿ƒåŠ›è¡°ç«­å¤§é¼ å¿ƒè‚Œçž¬æ—¶å—ä½“ç”µä½é¦™è‰é ¸äºšåž‹1ã€é™é’™ç´ åŸºå› ç›¸å ³è‚½è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on transient receptor potential vanilloid type 1(TRPV1), calcitonin gene-related peptide (CGRP), and serum interleukin-10 (IL-10) in the myocardial tissue of rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in improvement of CHF. METHODS: Male SD rats were randomly divided into the normal, model, moxibustion, capsaicin, moxibustion + capsaicin, and moxibustion + solvent groups, with 10 rats in each group. The CHF model was established by permanent ligation of the anterior descending branch of the left coronary artery. Mild moxibustion was applied to bilateral BL13 and BL15 for 30 min once daily for 4 weeks. Rats in the capsaicin group were smeared with capsaicin in the acupoint area once a day for 4 weeks. For rats of the moxibustion + capsaicin and moxibustion + solvent groups, capsaicin and solvent were applied to the acupoint area before moxibustion for 4 weeks, respectively. The ejection fraction (EF) and left ventricular fractional shortening rate (FS) were examined by echocardiography. HE staining was used to observe the myecardial morphological structure. The mRNA and protein expression levels of TRPV1, CGRP and galectin-3 (Gal-3) in myocardial tissue were detected by real-time quantitative PCR and Western blot, respectively. The content of IL-10 in serum was detected by ELISA. RESULTS: After modeling, the pathological changes of myocardium (as cardiac muscle fiber disorder, inflammatory cell infiltration, etc.) were obvious, and the EF, FS, serum IL-10, protein and mRNA exspression of TRPV1 and CGRP were significantly decreased (P<0.01) in the model group compared with the normal group, while the protein and mRNA exspression of Gal-3 were significantly up-regulated (P<0.01). Following the interventions, the above-mentioned indexes were all reversed in moxibustion, capsaicin, and moxibustion + capsaicin groups (P<0.01), and the effect of moxibustion + capsaicin was the best (P<0.05, P<0.01). CONCLUSIONS: Moxibustion can reduce myocardial injury and improve cardiac function in CHF rats, which may be related to its effects in up-regulating the expression of TRPV1 and CGRP, and down-regulating the expression of Gal-3 to alleviate myocardial fibrosis.

Knockdown H19 Accelerated iPSCs Reprogramming through Epigenetic Modifications and Mesenchymal-to-Epithelial Transition.

H19 is an essential imprinted gene that is expressed to govern normal embryonic development. During reprogramming, the parental pronuclei have asymmetric reprogramming capacities and the critical reprogramming factors predominantly reside in the male pronucleus. After inhibiting the expression of H19 and Gtl2, androgenetic haploid ESCs (AG-haESCs) can efficiently and stably support the generation of healthy SC pups at a rate of ~20%, and double-knockout parthenogenetic haESCs can also produce efficiently. Induced pluripotent stem (iPS) cell reprogramming is thought to have a characteristic epigenetic pattern that is the reverse of its developmental potential; however, it is unclear how H19 participates in iPS cell reprogramming. Here, we showed that the expression of H19 was transiently increased during iPSC reprogramming. H19 knockdown resulted in greater reprogramming efficiency. The genes associated with pluripotency showed enhanced expression during the early reprogramming process, and the Oct4 promoter was demethylated by bisulfite genomic sequencing analysis. Moreover, expression analysis revealed that the mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) were downregulated during reprogramming in H19 knockdown. These findings provide functional insight into the role of H19 as a barrier to the early reprogramming process.

Superb green cycling strategies for microbe-Fe0 neural network-type interaction: Harnessing eight key genes encoding enzymes and mineral transformations to efficiently treat PFOA.

To address time-consuming and efficiency-limited challenges in conventional zero-valent iron (ZVI, Fe0) reduction or biotransformation for perfluorooctanoic acid (PFOA) treatment, two calcium alginate-embedded amendments (biochar-immobilized PFOA-degrading bacteria (CB) and ZVI (CZ)) were developed to construct microbe-Fe0 high-rate interaction systems. Interaction mechanisms and key metabolic pathways were systematically explored using metagenomics and a multi-process coupling model for PFOA under microbe-Fe0 interaction. Compared to Fe0 (0.0076 day-1) or microbe (0.0172 day-1) systems, the PFOA removal rate (0.0426 day-1) increased by 1.5 to 4.6 folds in the batch microbe-Fe0 interaction system. Moreover, Pseudomonas accelerated the transformation of Fe0 into Fe3+, which profoundly impacted PFOA transport and fate. Model results demonstrated microbe-Fe0 interaction improved retardation effect for PFOA in columns, with decreased dispersivity a (0.48 to 0.20 cm), increased reaction rate λ (0.15 to 0.22 h-1), distribution coefficient Kd (0.22 to 0.46 cm3∙g-1), and fraction f´(52 % to 60 %) of first-order kinetic sorption of PFOA in microbe-Fe0 interaction column system. Moreover, intermediates analysis showed that microbe-Fe0 interaction diversified PFOA reaction pathways. Three key metabolic pathways (ko00362, ko00626, ko00361), eight functional genes, and corresponding enzymes for PFOA degradation were identified. These findings provide insights into microbe-Fe0 "neural network-type" interaction by unveiling biotransformation and mineral transformation mechanisms for efficient PFOA treatment.

Cutting-edge technologies and relevant reaction mechanism difference in treatment of long- and short-chain per- and polyfluoroalkyl substances: A review.

Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants. Compared with short-chain PFAS, long-chain PFAS are more hazardous. Currently, little attention has been paid to the differences in reaction mechanisms between long-chain and short-chain PFAS. This pressing concern has prompted studies about eliminating PFAS and revealing the mechanism difference. The reaction rate and reaction mechanism of each technology was focused on, including (1) adsorption, (2) ion exchange (IX), (3) membrane filtration, (4) advanced oxidation, (5) biotransformation, (6) novel functional material, and (7) other technologies (e.g. ecological remediation, hydrothermal treatment (HT), mechanochemical (MC) technology, micro/nanobubbles enhanced technology, and integrated technologies). The greatest reaction rate k of photocatalysis for long- and short-chain PFAS high up to 63.0 h-1 and 19.7 h-1, respectively. However, adsorption, membrane filtration, and novel functional material remediation were found less suitable or need higher operation demand for treating short-chain PFAS. Ecological remediation is more suitable for treating natural waterbody for its environmentally friendly and fair reaction rate. The other technologies all showed good application potential for both short- and long-chain PFAS, and it was more excellent for long-chain PFAS. The long-chain PFAS can be cleavaged into short-chain PFAS by C-chain broken, -CF2 elimination, nucleophilic substitution of F-, and HF elimination. Furthermore, the application of each type of technology was novelly designed; and suggestions for the future development of PFAS remediation technologies were proposed.

GDF11 mitigates high glucose-induced cardiomyocytes apoptosis by inhibiting the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway.

Diabetic cardiomyopathy remains a formidable health challenge with a high mortality rate and no targeted treatments. Growth differentiation factor 11 (GDF11) has shown promising effects on cardiovascular diseases; however, its role and the underlying mechanism in regulating diabetic cardiomyopathy remain unclear. In this study, we developed mouse models of diabetic cardiomyopathy using leptin receptor-deficient (db/db) mice and streptozocin-induced C57BL/6 mice. The diabetic cardiomyopathy model mice exhibited apparent structural damage in cardiac tissues and a significant increase in the expression of apoptosis-related proteins. Notably, we observed a significant decreased expression of GDF11 in the myocardium of mice with diabetic cardiomyopathy. Moreover, GDF11 cardiac-specific knock-in mice (transgenic mice) exhibited improved cardiac function and reduced apoptosis. Moreover, exogenous administration of GDF11 mitigated high glucose-induced cardiomyocyte apoptosis. Mechanistically, we demonstrated that GDF11 alleviated high glucose-induced cardiomyocytes apoptosis by inhibiting the activation of the alkylation repair homolog 5 (ALKBH5)-forkhead box group O3a (FOXO3)-cerebellar degeneration-related protein 1 transcript (CDR1as)/Hippo signaling pathway. Consequently, this novel mechanism effectively counteracted myocardial cell apoptosis, providing valuable insights into potential therapeutic strategies for clinical diabetic cardiomyopathy.

Uncovering hydrothermal treatment of per- and polyfluoroalkyl substances.

Image 1.

An Unusual Bismuth-Antimony-Europium Cluster-Imbedded Polyoxotungstate and Its Bidirectional Luminescence Detection.

An unprecedented aggregate formed by two bismuth-antimony-europium cluster-imbedded tungsten-oxo clusters and one Krebs-type polyoxotungstate linker [H2N(CH3)2]14Na30H6[W4O10][B-ß-BiW9O33]2{[Bi5.35Sb0.65Eu3O9(H2O)9][B-α-SbW9O33]3}2·124H2O (1) was prepared. The polyoxoanion skeleton of 1 contains a Krebs-type polyoxotungstate [W4O10][B-ß-BiW9O33]2}14- ({Bi2W22}) (1a) as a linker that offers six active coordinate O atoms (two µ3-O and four µ2-O atoms) to grasp two Bi-Sb-Eu cluster-imbedded tungsten-oxo clusters {[Bi5.35Sb0.65Eu3O9(H2O)9][B-α-SbW9O33]3}18- (1b) through Bi-O-W and Sb-O-W bonds. 1b comprises an unprecedented nona-nuclearity Bi-Sb-Eu [Bi5.35Sb0.65Eu3O9(H2O)9]9+ cluster encircled by three trivacant [B-α-SbW9O33]9-segments in a triangular motif through Eu-O-W, Sb-O-W, and Bi-O-W linkages into a trilobal trimer. Moreover, a bidirectional detection method by using 1 as an effective luminescence probe was proposed to recognize both Mn2+ and CO32- through an "on-off-on" mode. 1 can be used as an "on-off" luminescent sensor to detect Mn2+ ions in aqueous solution. The limit of detection was 0.05 µM (9 × 10-6 mg L-1), which is much lower than the World Health Organization (WHO) guideline for Mn2+ concentration in drinking water (0.05 mg L-1). Then the Mn2+-quenching system can be used as an "off-on" sensor to detect CO32- in water system. This work provides a new research idea for the application of rare-earth-imbedded polyoxotungstate-based materials in the field of optical smart detection.

Transport behavior difference and transport model of long- and short-chain per- and polyfluoroalkyl substances in underground environmental media: A review.

Perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonates (PFSAs), which are the most commonly regulated and most widely concerned per- and polyfluoroalkyl substances (PFAS) have received increasing attention on a global scale due to their amphiphilicity, stability, and long-range transport. Thus, understanding the typical PFAS transport behavior and using models to predict the evolution of PFAS contamination plumes is important for evaluating the potential risks. In this study, the effects of organic matter (OM), minerals, water saturation, and solution chemistry on the transport and retention of PFAS were investigated, and the interaction mechanism between long-chain/short-chain PFAS and the surrounding environment was analyzed. The results revealed that high content of OM/minerals, low saturation, low pH, and divalent cation had a great retardation effect on long-chain PFAS transport. The retention caused by hydrophobic interaction was the prominent mechanism for long-chain PFAS, whereas, the retention caused by electrostatic interaction was more relevant for short-chain PFAS. Additional adsorption at the air-water and nonaqueous-phase liquids (NAPL)-water interface was another potential interaction for retarding PFAS transport in the unsaturated media, which preferred to retard long-chain PFAS. Furthermore, the developing models for describing PFAS transport were investigated and summarized in detail, including the convection-dispersion equation, two-site model (TSM), continuous-distribution multi-rate model, modified-TSM, multi-process mass-transfer (MPMT) model, MPMT-1D model, MPMT-3D model, tempered one-sided stable density transport model, and a comprehensive compartment model. The research revealed PFAS transport mechanisms and provided the model tools, which supported the theoretical basis for the practical prediction of the evolution of PFAS contamination plumes.

GO accelerate iron oxides formation and tetrabromobisphenol A removal enhancement in the GO loaded NZVI system.

Tetrabromobisphenol A (TBBPA) is an emerging persistent organic pollutant, which is very difficult to remove by common methods. In this study, the GO-load nanoscale zero-valent iron (NZVI/GO) was fabricated and optimized to improve the reaction rate and removal efficiency for TBBPA reliably and efficiently. The results showed that GO-load significantly reduced the self-aggregation of NZVI and the aggregate size decreased by 50.00% (1400-700 nm). Meanwhile, GO significantly improved the reaction rate kobs (1.11 ± 0.11 h-1) of TBBPA in the NZVI/GO system compared to the NZVI (0.40 ± 0.08 h-1) system, and this increment was more pronounced (177.5%) when the mass ratio of NZVI-to-GO reached 1.0 than other mass ratios. Furthermore, X-Ray Diffraction and X-ray photoelectron spectroscopy analysis suggested that the Fe2+ transformation was changed and enriched by the GO. Only magnetite (Fe3O4) was detected on the surface of NZVI, whereas the maghemite (γ-Fe2O3), hematite (α-Fe2O3), and Fe3O4 were detected on the interface of NZVI/GO, which further performed the complexation adsorption through the -OH of TBBPA. This specific complexation adsorption is another potential accelerated removal mechanism for TBBPA and intermediates within the NZVI/GO system. This research has put forward a new perspective for widening the application of TBBPA removal using the synergistic effect between GO and NZVI.

Lanthanide-Incorporated Polyoxometalates Assembled from Mixed-Heteroatom-Oriented Three-Layered Cage Clusters.

Discovering innovative metal-oxo cluster materials with uncommon building blocks and exploiting their application potentiality are fairly challengeable. Here, we provide a novel type of lanthanide-incorporated polyoxometalates [H2N(CH3)2]10Na8H6{[Ln0.5/Na0.5(HGCA)(H2O)1.5]2[(BiO3)(SeO3)2W21O66]2}·36H2O [Ln = Eu3+ (1), Er3+ (2), H2GCA = α-glycolic acid] synthesized by a dual-heteroatom-directed synergetic strategy, which are established from two unique BiIII-SeIV heteroatom-oriented cylindrical three-layered [(BiO3)(SeO3)2W21O66]13- cage clusters integrated by lanthanide-organic groups. Compound 1 works as a fluorescence probe for high-sensitivity detection toward a neurotransmitter dopamine. This finding not only shows the enormous possibility and feasibility to create novel polyoxometalate building units by means of the self-categorization of different heteroatoms, which are subsequently employed for further assembly chemistry, but also provides a platform to exploit latent utilizations of polyoxometalate-based materials in the realm of detecting biological molecules.

Identification of microRNAs related with neural germ layer lineage-specific progenitors during reprogramming.

Differentiated cells can be reprogrammed to embryonic stem cell-like cells called induced pluripotent stem cells (iPSCs), in which the natural developmental differentiation process is reversed. It is unclear whether the multi-lineage cells can be isolated and identified during reprogramming. In the current study, we detected the expression of lineage markers, isolated neural lineages, and identified the related microRNAs during iPSC formation. Our results demonstrated that a neuroectoderm appeared earlier than mesoderm and definitive endoderm before forming colonies when mouse embryonic fibroblasts were subjected to iPSC formation using transcription factors (TFs). On day 3, the cells expressed Sox1 and Nestin and had ultrastructure consistent with the transition to identity neural germ layer lineage. Fluorescence-activated cell sorting analysis revealed a peak (40%) in neural progenitor marker-positive cells. When subsequently cultured in a neural precursor cell medium, these cells proliferated slowly, became round and aggregated, generating into neurons and glia. Genome-wide microRNA (miRNA) analysis identified 45 differentially regulated miRNAs. Molecular network analysis demonstrated that these miRNAs validated 6,047 experimental mRNA targets. The GO functional annotation analysis of mRNA targets revealed that most genes were related to neurogenesis, such as growth cone, neuronal cell body, neuron projection, and cell junction synapse. The network of protein-protein interactions was observed, which demonstrated that key nodes of neural lineage reprogramming-associated targets were Sall1, Foxa2, Nf2, Ctnnb1, Shh, and Bmpr1a. Therefore, these data suggested that TFs can drive the reprogramming of somatic cells towards a pluripotent state via neuroectoderm. Moreover, the neural lineage reprogramming system can address how miRNAs influence their target sites.

Parental preference for influenza vaccine for children in China: a discrete choice experiment.

OBJECTIVES: To investigate what factors affect parents' influenza vaccination preference for their children and whether there exists preference heterogeneity among respondents in China. DESIGN: Cross-sectional study. A discrete choice experiment was conducted. Five attributes were identified based on literature review and qualitative interviews, including protection rate, duration of vaccine-induced protection, risk of serious side effects, location of manufacturer and out-of-pocket cost. SETTING: Multistage sampling design was used. According to geographical location and the level of economic development, 10 provinces in China were selected, and the survey was conducted at community healthcare centres or stations. PARTICIPANTS: Parents with at least one child aged between 6 months and 5 years old were recruited and the survey was conducted via a face-to-face interview in 2019. In total, 600 parents completed the survey, and 449 who passed the internal consistency test were included in the main analysis. MAIN OUTCOMES AND MEASURES: A mixed logit model was used to estimate factors affecting parents' preference to vaccinate their children. In addition, sociodemographic characteristics were included to explore the preference heterogeneity. RESULTS: In general, respondents preferred to vaccinate their children. All attributes were statistically significant and among them, the risk of severe side effects was the most important attribute, followed by the protection rate and duration of vaccine-induced protection. Contrary to our initial expectation, respondents have a stronger preference for the domestic than the imported vaccine. Some preference heterogeneity among parents was also found and in particular, parents who were older, or highly educated placed a higher weight on a higher protection rate. CONCLUSION: Vaccination safety and vaccine effectiveness are the two most important characteristics that influenced parents' decision to vaccinate against influenza for their children in China. Results from this study will facilitate future policy implementations to improve vaccination uptake rates.

The multi-process reaction model and underlying mechanisms of 2,4,6-trichlorophenol removal in lab-scale biochar-microorganism augmented ZVI PRBs and field-scale PRBs performance.

This work developed calcium alginate (CA) embedded zero-valent iron (ZVI@CA) and CA embedded biochar (BC) immobilized microorganism (BC&Cell@CA) gel beads as alternative to conventional Fe0 permeable reactive barriers for treating groundwater contaminated with 2,4,6-trichlorophenol (2,4,6-TCP). Lab-scale and field-scale biochar-microorganism augmented PRBs (Bio-PRBs) were constructed and tested. The underlying mechanisms were revealed by a multi-source data calibrated multi-process reaction model, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and high-throughput sequencing. Moreover, calibrated advection-dispersion (a) coupled with the two-site sorption (Kd) and chemical-biological multi-process reaction (λ) model were used for revealing 2,4,6-TCP transport behavior and optimizing Bio-PRBs. Compared to that in the ZVI@CA (0.004 h-1) system, the reaction rate (0.011 h-1) of 2,4,6-TCP increased by 175% in the combined chemical-biological batch system. Moreover, chemical-biological augmentation significantly improved the retardation effect of Bio-PRBs for 2,4,6-TCP. It came from that chemical-biological augmentation significantly decreased the dispersivity a (0.53 to 0.20 cm), and increased the distribution coefficient Kd (2.20 to 19.00 cm3 mg-1), the reaction rate λ (2.40 to 3.60 day-1), and the fraction (30% to 80%) of first-order kinetic sorption of 2,4,6-TCP in the lab-scale one-dimensional Bio-PRBs. Moreover, versatile functional bacteria Desulfitobacterium was crucial in the transformation of Fe (III) iron oxides. The diversity and richness of archaea in the reaction solution were improved by ZVI@CA gel beads addition. Furthermore, the field-scale reaction system was designed to remediate the chlorinated organic compounds and Benzene Toluene Ethylbenzene & Xylene contaminated groundwater in a pesticide factory site. The field test results demonstrated it is a promising technology to construct vertical reaction columns or horizontal Bio-PRBs for the efficient remediation of actually contaminated groundwater.

Identification and Molecular Analysis of m6A-circRNAs from Cashmere Goat Reveal Their Integrated Regulatory Network and Putative Functions in Secondary Hair Follicle during Anagen Stage.

N6-methyladenosine (m6A) is the most abundant modification in linear RNA molecules. Over the last few years, interestingly, many circRNA molecules are also found to have extensive m6A modification sites with temporal and spatial specific expression patterns. To date, however, little information is available concerning the expression profiling and functional regulatory characteristics of m6A modified circRNAs (m6A-circRNAs) in secondary hair follicles (SHFs) of cashmere goats. In this study, a total of fifteen m6A-circRNAs were identified and characterized in the skin tissue of cashmere goats. Of these, six m6A-circRNAs were revealed to have significantly higher expression in skin at anagen compared with those at telogen. The constructed ceRNA network indicated a complicated regulatory relationship of the six anagen up-regulated m6A-circRNAs through miRNA mediated pathways. Several signaling pathways implicated in the physiological processes of hair follicles were enriched based on the potential regulatory genes of the six anagen up-regulated m6A-circRNAs, such as TGF-beta, axon guidance, ribosome, and stem cell pluripotency regulatory pathways, suggesting the analyzed m6A-circRNAs might be essentially involved in SHF development and cashmere growth in cashmere goats. Further, we showed that four m6A-circRNAs had highly similar expression trends to their host genes in SHFs of cashmere goats including m6A-circRNA-ZNF638, -TULP4, -DNAJB6, and -CAT. However, the expression patterns of two m6A-circRNAs (m6A-circRNA-STAM2 and -CAAP1) were inconsistent with the linear RNAs from their host genes in the SHFs of cashmere goats. These results provide novel information for eluci-dating the biological function and regulatory characteristics of the m6A-circRNAs in SHF development and cashmere growth in goats.

Nicotinic-Acid-Ornamented Tetrameric Rare-Earth-Substituted Phospho(III)tungstates with the Coexistence of Mixed Keggin/Dawson Building Blocks and Its Honeycomb Nanofilm for Detecting Toxins.

A fascinating class of nicotinic-acid-ornamented tetrameric rare-earth (RE)-substituted phospho(III)tungstates [NH2(CH3)2]10Na4H8[RE2(NA)(HNA)(H2O)6(W2O4)(ß-H2P2IIIW13O49)(α-HPIIIW9O33)]2·22 H2O [RE = Nd3+ (1-Nd), Tb3+ (2-Tb), Dy3+ (3-Dy), Ho3+ (4-Ho), HNA = nicotinic acid] were isolated through a one-step reaction method of Na2WO4·2H2O, H3PO3, HNA, NH2(CH3)2·HCl, and RE(NO3)·6H2O. Of meticulous concern is that HPO32- was used as a template to construct tetrameric RE-substituted phospho(III)tungstates including mixed heteropolyoxotungstate building blocks. Their hybrid polyoxoanions are composed of two symmetrical [RE2(NA)(HNA)(H2O)6(W2O4)(ß-H2P2IIIW13O49)(α-HPW9O33)]11- units linked by RE-O-W bonds. The symmetrical unit consists of one peculiar heterometal nicotinic-acid-ornamented [RE2(NA)(HNA)(W2O4)]9+ cluster connecting a pentavacant Dawson-like [ß-H2P2W13O49]12- and a trivacant Keggin [α-HPW9O33]8- subunits. Furthermore, dimethyldioctadecylammonium chloride (DMDODA·Cl) was used to combine with 1-Nd in the CHCl3-H2O system through electrostatic interactions, leading to the 1-Nd@DMDODA composite material. The honeycomb-patterned film of the 1-Nd @DMDODA composite material was successfully constructed by using the breath figure method on a glassy carbon electrode, which can offer abundant binding sites to Au nanoparticles (nano-Au). Ulteriorly, Au-functionalized 1-Nd@DMDODA-modified electrode was utilized as an electrochemical sensor to detect ochratoxin A, showing a good detection limit of 1.19 pM.

Job preferences of undergraduate pharmacy students in China: a discrete choice experiment.

BACKGROUND: Pharmacists are a crucial part of the health workforce and play an important role in achieving universal health coverage. In China, pharmaceutical human resources are in short supply, and the distribution is unequal. This study aimed to identify the key job characteristics that influence the job preferences of undergraduate pharmacy students and to elicit the relative importance of different job characteristics to shed light on future policy interventions. METHODS: A discrete choice experiment was conducted to assess the job preferences of undergraduate pharmacy students from 6 provinces in mainland China. A face-to-face interview was used to collect data. Conditional logit and mixed logit models were used to analyse data, and the final model was chosen according to the model fit statistics. A series of policy simulations was also conducted. RESULTS: In total, 581 respondents completed the questionnaire, and 500 respondents who passed the internal consistency test were analysed. All attributes were statistically significant except for open management. Monthly income and work location were most important to respondents, followed by work unit (which refers to the nature of the workplace) and years to promotion. There was preference heterogeneity among respondents, e.g., male students preferred open management, and female students preferred jobs in public institutions. Furthermore, students with an urban background or from a single-child family placed higher value on a job in the city compared to their counterparts. CONCLUSION: The heterogeneity of attributes showed the complexity of job preferences. Both monetary and nonmonetary job characteristics significantly influenced the job preferences of pharmacy students in China. A more effective policy intervention to attract graduates to work in rural areas should consider both incentives on the job itself and the background of pharmacy school graduates.

Parental Vaccine Preferences for Their Children in China: A Discrete Choice Experiment.

Background: Vaccination is one of the most cost-effective health investments to prevent and control communicable diseases. Improving the vaccination rate of children is important for all nations, and for China in particular since the advent of the two-child policy. This study aims to elicit the stated preference of parents for vaccination following recent vaccine-related incidents in China. Potential preference heterogeneity was also explored among respondents. Methods: A discrete choice experiment was developed to elicit parental preferences regarding the key features of vaccines in 2019. The study recruited a national sample of parents from 10 provinces who had at least one child aged between 6 months and 5 years old. A conditional logit model and a mixed logit model were used to estimate parental preference. Results: A total of 598 parents completed the questionnaire; among them, 428 respondents who passed the rational tests were analyzed. All attributes except for the severity of diseases prevented by vaccines were statistically significant. The risk of severe side effects and protection rates were the two most important factors explaining parents' decisions about vaccination. The results of the mixed logit model with interactions indicate that fathers or rural parents were more likely to vaccinate their children, and children whose health was not good were also more likely to be vaccinated. In addition, parents who were not more than 30 years old had a stronger preference for efficiency, and well-educated parents preferred imported vaccines with the lowest risk of severe side effects. Conclusion: When deciding about vaccinations for their children, parents in China are mostly driven by vaccination safety and vaccine effectiveness and were not affected by the severity of diseases. These findings will be useful for increasing the acceptability of vaccination in China.

Nanocrystal Formulation Improves Vaginal Delivery of CSIC for HIV Prevention.

5-Chloro-3-phenylsulfonylindole-2-carboxamide (CSIC) is a highly potent non-nucleoside reverse transcriptase inhibitor (NNRTI) with potential for use in topical prophylaxis against HIV transmission. However, the hydrophobic nature of CSIC limits its administration through vaginal route. In this study, we developed nanocrystals of CSIC to potentially improve the aqueous solubility and intracellular uptake of CSIC in vitro and in vivo. CSIC nanocrystals were manufactured and stabilized with Pluronic F98 and hydroxypropyl methylcellulose E5. Transmission electron microscopy showed CSIC nanocrystals to be needle-like. Dynamic light scattering measurements showed a hydrodynamic size of 243 nm (polydispersity index < 0.3) and near neutral surface charge (- 7.8 mV). Particle size was maintained for at least 7 days in the liquid state and for at least 5 months after lyophilization. Drug content in the CSIC nanocrystal formulation (nanosuspension) was 0.8 mg/mL, which is 1000 times higher than the aqueous solubility of CSIC. In vitro release study showed that over 90% of CSIC was released from the nanocrystal formulation in a linear fashion over a period of 4 days. Importantly, CSIC nanocrystals showed equivalent cell-based anti-HIV activity (EC50 ~ 1 nM) as that of non-formulated drug. In vitro studies demonstrated rapid macrophage uptake of CSIC nanocrystals via both energy-dependent (endocytosis) and independent processes. In vivo studies in Swiss Webster female mice showed that the nanocrystal formulation significantly improved CSIC delivery to mouse cervicovaginal tissues following intravaginal instillation. In summary, nanocrystals are a promising formulation approach for topical delivery of CSIC for protection against HIV sexual transmission.

Rapamycin and FTY720 Alleviate Atherosclerosis by Cross Talk of Macrophage Polarization and Autophagy.

Foam cell formation and macrophage polarization are involved in the pathologic development of atherosclerosis, one of the most important human diseases affecting large and medium artery walls. This study was designed to assess the effects of rapamycin and FTY720 (fingolimod) on macrophages and foam cells. Mouse peritoneal macrophages were collected and treated with rapamycin and FTY720 to study autophagy, polarization, and lipid accumulation. Next, foam cells were formed by oxidizing low-density lipoprotein to observe changes in lipid accumulation, autophagy, and polarization in rapamycin-treated or FTY720-treated foam cells. Lastly, foam cells that had been treated with rapamycin and FTY720 were evaluated for sphingosine 1-phosphate receptor (S1prs) expression. Autophagy microtubule-associated protein 1 light chain 3- (LC3-) II was increased, and classically activated macrophage phenotype markers interleukin- (IL-) 6, cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS) were increased, whereas alternatively activated macrophage phenotype markers transforming growth factor- (TGF-) ß, arginase 1 (Arg1), and mannose receptor C-type 1 (Mrc1) were decreased by rapamycin in peritoneal macrophages. LC3-II was also obviously enhanced, though polarization markers were unchanged in rapamycin-treated foam cells. Moreover, lipid accumulation was inhibited in rapamycin-treated macrophage cells but was unchanged in rapamycin-treated foam cells. For FTY720, LC3-II did not change, whereas TGF-ß, Arg1 and Mrc1 were augmented, and IL-6 was suppressed in macrophages. However, LC3-II was increased, and TGF-ß, ARG1 and MRC1 were strikingly augmented, whereas IL-6, COX2 and iNOS could be suppressed in foam cells. Furthermore, lipid accumulation was alleviated in FTY720-treated foam cells. Additionally, S1pr1 was markedly decreased in foam cells (P < .05); S1pr2, S1pr3, S1pr4 and S1pr5 were unchanged in rapamycin-treated foam cells. In FTY720-treated foam cells, S1pr3 and S1pr4 were decreased, and S1pr1, S1pr2 and S1pr5 were unchanged. Therefore, we deduced that rapamycin stimulated classically activated macrophages and supressed early atherosclerosis. Rapamycin may also stabilize artery plaques by preventing apoptosis and S1PR1 in advanced atherosclerosis. FTY720 allowed transformation of foam cells into alternatively activated macrophages through the autophagy pathway to alleviate advanced atherosclerosis.