Studying the role of Bombyx mori molybdenum cofactor sulfurase in Bombyx mori nucleopolyhedrovirus infection.

Molybdenum cofactor sulfurase (MoCoS) is a key gene involved in the uric acid metabolic pathway that activates xanthine dehydrogenase to synthesise uric acid. Uric acid is harmful to mammals but plays crucial roles in insects, one of which is the immune responses. However, the function of Bombyx mori MoCoS in response to BmNPV remains unclear. In this study, BmMoCoS was found to be relatively highly expressed in embryonic development, gonads and the Malpighian tubules. In addition, the expression levels of BmMoCoS were significantly upregulated in three silkworm strains with different levels of resistance after virus infection, suggesting a close link between them. Furthermore, RNAi and overexpression studies showed that BmMoCoS was involved in resistance to BmNPV infection, and its antivirus effects were found to be related to the regulation of uric acid metabolism, which was uncovered by inosine- and febuxostat-coupled RNAi and overexpression. Finally, the BmMoCoS-mediated uric acid pathway was preliminarily confirmed to be a potential target to protect silkworms from BmNPV infection. Overall, this study provides new evidence for elucidating the molecular mechanism of silkworms in response to BmNPV infection and new strategies for the prevention of viral infections in sericulture.

Uridine diphosphate glucosyltransferase is vital for fenpropathrin resistance in Bombyx mori (Lepidoptera).

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

[Pharmacokinetics of 11 active components of Psoraleae Fructus in normal and diabetic rats].

A total of 11 active ingredients including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, coryfolin, isobavachalcone, neobavaisoflavone, bakuchalcone, and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated to elucidate the pharmacokinetic profiles of coumarins, flavonoids, and monoterpene phenols in normal and diabetic rats. The rat model of type 2 diabetes mellitus(T2DM) was induced by a high-sugar and high-fat diet combined with injection of 1% streptozotocin every two days. The plasma samples were collected at different time points after the rats were administrated with Psoraleae Fructus. The proteins in the plasma samples were precipitated by ethyl acetate, and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS 3.0. The results showed that the pharmacokinetic beha-viors of 8 components including psoralen, isopsoralen, bakuchiol, and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats. Among them, the coumarins including psoralen, isopsoralen, and corylin showed lowered levels in the blood of both female and male model rats. The flavonoids(bavachinin, corylifol A, and bakuchalcone) and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats. It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clinical administration.

Uric acid metabolism promotes apoptosis against Bombyx mori nucleopolyhedrovirus in silkworm, Bombyx mori.

The white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine-fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

BACKGROUND: Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry. METHODS: Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency. RESULTS: The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites). CONCLUSIONS: The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

Boron-based Pd3B26 alloy cluster as a nanoscale antifriction bearing system: tubular core-shell structure, double π/σ aromaticity, and dynamic structural fluxionality.

Boron-based nanoclusters show unique geometric structures, nonclassical chemical bonding, and dynamic structural fluxionality. We report here on the theoretical prediction of a binary Pd3B26 cluster, which is composed of a triangular Pd3 core and a tubular double-ring B26 unit in a coaxial fashion, as identified through global structural searches and electronic structure calculations. Molecular dynamics simulations indicate that in the core-shell alloy cluster, the B26 double-ring unit can rotate freely around its Pd3 core at room temperature and beyond. The intramolecular rotation is virtually barrier free, thus giving rise to an antifriction bearing system (or ball bearing) at the nanoscale. The dimension of the dynamic system is only 0.66 nm. Chemical bonding analysis reveals that Pd3B26 cluster possesses double 14π/14σ aromaticity, following the (4n + 2) Hückel rule. Among 54 pairs of valence electrons in the cluster, the overwhelming majority are spatially isolated from each other and situated on either the B26 tube or the Pd3 core. Only one pair of electrons are primarily responsible for chemical bonding between the tube and the core, which greatly weaken the bonding within the Pd3 core and offers structural flexibility. This is a key mechanism that effectively diminishes the intramolecular rotation barrier and facilitates dynamic structural fluxionality of the system. The current work enriches the field of nanorotors and nanomachines.

Production improvement of FK506 in Streptomyces tsukubaensis by metabolic engineering strategy.

AIMS: Study of the effect of isoleucine on the biosynthesis of FK506 and modification of its producing strain to improve the production of FK506. METHODS AND RESULTS: Metabolomics analysis was conducted to explore key changes in the metabolic processes of Streptomyces tsukubaensis Δ68 in medium with and without isoleucine. In-depth analysis revealed that the shikimate pathway, methylmalonyl-CoA, and pyruvate might be the rate-limiting factors in FK506 biosynthesis. Overexpression of involved gene PCCB1 in S. tsukubaensis Δ68, a high-yielding strain Δ68-PCCB1 was generated. Additionally, the amino acids supplement was further optimized to improve FK506 biosynthesis. Finally, FK506 production was increased to 929.6 mg L-1, which was 56.6% higher than that in the starter strain, when supplemented isoleucine and valine at 9 and 4 g L-1, respectively. CONCLUSIONS: Methylmalonyl-CoA might be the key rate-limiting factors in FK506 biosynthesis and overexpression of the gene PCCB1 and further addition of isoleucine and valine could increase the yield of FK506 by 56.6%.

Transcriptomic analysis of the fat body of resistant and susceptible silkworm strains, Bombyx mori (Lepidoptera), after oral treatment with fenpropathrin.

The widespread use of pyrethroid pesticides has brought serious economic losses in sericulture, but there is still no viable solution. The key to solving the problem is to improve silkworm resistance to pesticides, which depends on understanding the resistance mechanism of silkworms to pesticides. This study aimed to use transcriptomes to understand the underlying mechanism of silkworm resistance to fenpropathrin, which will provide a theoretical molecular reference for breeding pesticide-resistant silkworm varieties. In this study, the fat bodies of two strains with differential resistance after 12 h of fenpropathrin feeding were analyzed using RNA-Seq. After feeding fenpropathrin, 760 differentially expressed genes (DEGs) were obtained in the p50(r) strain and 671 DEGs in the 8y strain. The DEGs involved in resistance to fenpropathrin were further identified by comparing the two strains, including 207 upregulated DEGs in p50(r) and 175 downregulated DEGs in 8y. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these fenpropathrin-related DEGs are mainly enriched in the metabolism and transporter pathways. Moreover, 28 DEGs involved in the metabolic pathway and 18 in the transporter pathway were identified. Furthermore, organic cation transporter protein 6 (BmOCT6), a transporter pathway member, was crucial in enhancing the tolerance of BmN cells to fenpropathrin. Finally, the knockdown of the expression of the homologs of BmOCT6 in Glyphodes pyloalis (G. pyloalis) significantly decreased the resistant level of larvae to fenpropathrin. The findings showed that the metabolism and transporter pathways are associated with resistance to fenpropathrin in silkworm, and OCT6 is an effective and potential target not only for silkworm breeding but also for pest biocontrol.

[Anti-endothelial cell antibodies in predicting early miscarriage].

OBJECTIVE: To explore the clinical significance of anti-endothelial cell antibodies (AECA) in predicting early miscarriage. METHODS: A total of 122 pregnant women with no history of autoimmune diseases who underwent prenatal examination at Peking University People's Hospital from January 2020 to December 2022 were selected, and they were tested for AECA. Based on the history of early miscarriage (gestational age at miscarriage < 12 weeks), the participants were divided into an early miscarriage group and a control group. t-tests, non-parametric Wilcoxon tests, Chi-square tests, and Fisher's exact probability method were used to compare general information and laboratory indicators between the two groups. A multivariate Logistic regression model was used to analyze the factors associated with early miscarriage. The natural miscarriage rates were assessed through follow-up with pregnant women, and Kaplan-Meier survival analysis was employed to compare the natural miscarriage rates between AECA-positive and AECA-negative pregnant women. RESULTS: (1) A total of 122 pregnant women were enrolled, comprising 35 cases (28.7%) in the early miscarriage group, with an average age of (32.1±6.1) years, and 87 cases (71.3%) in the control group, with an average age of (30.7±5.1) years. The early miscarriage group had higher gravidity [3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001] and a higher prevalence of hypertension (11.4% vs.1.1%, P=0.024). The positive rate of AECA in the early miscarriage group (34.3% vs. 8.0%, χ2=13.070, P < 0.001) and the proportion of elevated immunoglobulin G (17.1% vs. 4.6%, P=0.032) were significantly higher than that in the control group. (2) Multivariate logistic regression analysis showed that higher gravidity (OR=4.149, 95%CI: 2.287-7.529, P < 0.001), AECA positivity (OR= 4.288, 95% CI: 1.157-15.893, P=0.029), and elevated immunoglobulin G levels (OR =6.177, 95%CI: 1.156-33.015, P=0.033) were risk factors for early miscarriage. (3) The 122 pregnant women were categorized into two groups: the AECA-positive group (19 cases) and the AECA-negative group (103 cases). Survival analysis demonstrated that at the end of 12 weeks of gestation, the fetal survival rate in the AECA-positive group was significantly lower than that in the AECA-negative group (84.2% vs. 96.1%, P= 0.035). CONCLUSION: Higher gravidity, AECA positivity, and elevated immunoglobulin G levels are significant risk factors for early miscarriage. The results demonstrate that AECA is a novel predicting test in early miscarriage.

Deposition Mechanism and Properties of Plasma-Enhanced Atomic Layer Deposited Gallium Nitride Films with Different Substrate Temperatures.

Gallium nitride (GaN) is a wide bandgap semiconductor with remarkable chemical and thermal stability, making it a competitive candidate for a variety of optoelectronic applications. In this study, GaN films are grown using a plasma-enhanced atomic layer deposition (PEALD) with trimethylgallium (TMG) and NH3 plasma. The effect of substrate temperature on growth mechanism and properties of the PEALD GaN films is systematically studied. The experimental results show that the self-limiting surface chemical reactions occur in the substrate temperature range of 250-350 °C. The substrate temperature strongly affects the crystalline structure, which is nearly amorphous at below 250 °C, with (100) as the major phase at below 400 °C, and (002) dominated at higher temperatures. The X-ray photoelectron spectroscopy spectra reveals the unintentional oxygen incorporation into the films in the forms of Ga2O3 and Ga-OH. The amount of Ga-O component decreases, whereas the Ga-Ga component rapidly increases at 400 and 450 °C, due to the decomposition of TMG. The substrate temperature of 350 °C with the highest amount of Ga-N bonds is, therefore, considered the optimum substrate temperature. This study is helpful for improving the quality of PEALD GaN films.

Sustainable and Robust Graphene Cellulose Paper Decorated with Lithiophilic Au Nanoparticles to Enable Dendrite-free and High-Power Lithium Metal Anode.

Lithium metal anodes (LMAs) with high energy density have recently captured increasing attention for development of next-generation batteries. However, practical viability of LMAs is hindered by the uncontrolled Li dendrite growth and infinite dimension change. Even though constructing 3D conductive skeleton has been regarded as a reliable strategy to prepare stable and low volume stress LMAs, engineering the renewable and lithiophilic conductive scaffold is still a challenge. Herein, a robust conductive scaffold derived from renewable cellulose paper, which is coated with reduced graphene oxide and decorated with lithiophilic Au nanoparticles, is engineered for LMAs. The graphene cellulose fibres with high surface area can reduce the local current density, while the well-dispersed Au nanoparticles can serve as lithiophilic nanoseeds to lower the nucleation overpotential of Li plating. The coupled relationship can guarantee uniform Li nucleation and unique spherical Li growth into 3D carbon matrix. Moreover, the natural cellulose paper possesses outstanding mechanical strength to tolerate the volume stress. In virtue of the modulated deposition behaviour and near-zero volume change, the hybrid LMAs can achieve reversible Li plating/stripping even at an ultrahigh current density of 10 mA cm-2 as evidenced by high Coulombic efficiency (97.2 % after 60 cycles) and ultralong lifespan (1000 cycles) together with ultralow overpotential (25 mV). Therefore, this strategy sheds light on a scalable approach to multiscale design versatile Li host, promising highly stable Li metal batteries to be feasible and practical.

Improvement of FK506 production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis.

BACKGROUND: FK506, a macrolide mainly with immunosuppressive activity, can be produced by various Streptomyces strains. However, one of the major challenges in the fermentation of FK506 is its insufficient production, resulting in high fermentation costs and environmental burdens. Herein, we tried to improve its production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis. RESULTS: First, basing on the genome sequencing and analysis, putative competitive pathways were deleted. A better parental strain L19-2 with increased FK506 production from 140.3 to 170.3 mg/L and a cleaner metabolic background was constructed. Subsequently, the FK506 biosynthetic gene cluster was refactored by in-situ promoter-substitution strategy basing on the regulatory circuits. This strategy enhanced transcription levels of the entire FK506 biosynthetic gene cluster in a fine-tuning manner and dramatically increased the FK506 production to 410.3 mg/mL, 1.41-fold higher than the parental strain L19-2 (170.3 mg/L). Finally, the FK506 production was further increased from 410.3 to 603 mg/L in shake-flask culture by adding L-isoleucine at a final concentration of 6 g/L. Moreover, the potential of FK506 production capacity was also evaluated in a 15-L fermenter, resulting in the FK506 production of 830.3 mg/L. CONCLUSION: From the aspects of competitive pathways, refactoring of the FK506 biosynthetic gene cluster and nutrients-addition, a strategy for hyper-production and potentially industrial application of FK506 was developed and a hyper-production strain L19-9 was constructed. The strategy presented here can be generally applicable to other Streptomyces for improvement of FK506 production and streamline hyper-production of other valuable secondary metabolites.

EM-2 inhibited autophagy and promoted G2/M phase arrest and apoptosis by activating the JNK pathway in hepatocellular carcinoma cells.

This study aimed to investigate the inhibitory effect of EM-2, a natural active monomer purified from Elephantopusmollis H.B.K., on the proliferation of human hepatocellular carcinoma cells and the molecular mechanism involved. The results from the MTT assay revealed that EM-2 significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) cells in a dose-dependent manner but exhibited less cytotoxicity to the normal liver epithelial cell line LO2. EdU staining and colony formation assays further confirmed the inhibitory effect of EM-2 on the proliferation of Huh-7 hepatocellular carcinoma cells. According to the RNA sequencing and KEGG enrichment analysis results, EM-2 markedly activated the MAPK pathway in Huh-7 cells, and the results of Western blotting further indicated that EM-2 could activate the ERK and JNK pathways. Meanwhile, EM-2 induced apoptosis in a dose-dependent manner and G2/M phase arrest in Huh-7 cells, which could be partially reversed when treated with SP600125, a JNK inhibitor. Further study indicated that EM-2 induced endoplasmic reticulum stress and blocked autophagic flux in Huh-7 cells by inhibiting autophagy-induced lysosome maturation. Inhibition of autophagy by bafilomycin A1 could reduce cell viability and increase the sensitivity of Huh-7 cells to EM-2. In conclusion, our findings revealed that EM-2 not only promoted G2/M phase arrest and activated ER stress but also induced apoptosis by activating the JNK pathway and blocked autophagic flux by inhibiting autolysosome maturation in Huh-7 hepatocellular carcinoma cells. Therefore, EM-2 is a potential therapeutic drug with promising antitumor effects against hepatocellular carcinoma and fewer side effects.

Activation and discovery of tsukubarubicin from Streptomyces tsukubaensis through overexpressing SARPs.

Genome sequencing has revealed that each Streptomyces contains a wide range of biosynthetic gene clusters (BGCs) and has the capability to produce more novel natural products than what is expected. However, most gene clusters for secondary metabolite biosynthesis are cryptic under normal growth conditions. In Streptomyces tsukubaensis, combining overexpression of the putative SARPs (Streptomyces antibiotic regulatory proteins) and bioactivity-guided screening, the silent gene cluster (tsu) was successfully activated and a novel bioactive anthracycline tsukubarubicin was further isolated and identified. Biological activity assays demonstrated that tsukubarubicin possessed much better antitumor bioactivities against various human cancer cell lines (especially the breast cancer cell lines) than clinically used doxorubicin. Moreover, the previously unreported gene cluster (tsu) for biosynthesis of tsukubarubicin was first characterized and detailed annotations of this gene cluster were also conducted. Our strategy presented in this work is broadly applicable in other Streptomyces and will assist in enriching the natural products for potential drug leads. KEY POINTS: • Generally scalable strategy to activate silent gene clusters by manipulating SARPs. • The novel anthracycline tsukubarubicin with potent antitumor bioactivities. • Identification and annotation of the previously uncharacterized tsu gene cluster.

Effectiveness of adjuvant supportive-expressive group therapy for breast cancer.

PURPOSE: Randomized control trials exploring adjuvant supportive-expressive group therapy (SEGT) for breast cancer have yielded conflicting survival results. This retrospective cohort study was designed to explore the association of adjuvant SEGT performed at diagnosis with survival in real-world patients. METHODS: 3327 patients with breast cancer were divided between those who received oncologic treatment combined with SEGT-based intervention (referred to as BRBC [n = 354]) and those who only received oncologic treatment (referred to as OT [n = 2973]). Primary outcome was overall survival (OS) at 1-year, 3-year, 5-year. Propensity score-matched analysis (at a ratio of 1:3) and instrumental variable analysis (IVA) were performed. RESULTS: The median overall survival was 7.3 years (95% CI 7.0-7.7 years) in BRBC and 7.1 years (95% CI 6.9-7.4 years) in OT. BRBC was not significantly associated with improved 1-year (HR 0.74, 95% CI 0.49-1.10, P = 0.1748; NNT = 44.8, 95% CI - 118.5 to 22.6), 3-year (HR 0.98, 95% CI 0.75-1.27, P = 0.8640; NNT = 273.7, 95% CI - 21.0 to 21.3), or 5-year survival (HR 0.79, 95% CI 0.61-1.02, P = 0.0908; NNT = 36.0, 95% CI - 384.5 to 19.1) compared with OT. IVA indicated that BRBC had a survival benefit over OT in the 1-year, 3-year, and 5-year of 1.5% (95% CI 1.2-1.9%), 0.7% (95% CI 0.6-0.8%), and 2.6% (95% CI 2.0-3.4%), respectively. CONCLUSION: Adjuvant SEGT cannot significantly prolong 5-year survival in breast cancer, though a longer observation period is warranted according to the marginal survival benefit identified at the end of the follow-up.

Minimum clinical important difference for resilience scale specific to cancer: a prospective analysis.

BACKGROUND: The minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25). METHODS: From June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs. RESULTS: 623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38-0.44, all p < 0.001). Linear regression estimated + 8.9 and - 6.7 as the MCIDs of RS-SC-25, and + 3.4 and - 2.5 for RS-SC-10. Distribution-based methods estimated + 9.9 and - 9.9 as the MCIDs of RS-SC-25, and + 4.0 and - 4.0 for RS-SC-10. ROC estimated + 5.5 and - 4.5 as the MCIDs of RS-SC-25, and + 2.0 and - 1.5 for RS-SC-10. CONCLUSIONS: The most reliable MCID is around 5 points for RS-SC-25 and 2 points for RS-SC-10. RS-SCs are more responsive to the worsening status of resilience in patients with cancer and these estimates could be useful in future resilience-based intervention trials.

Air Annealing Effect on Oxygen Vacancy Defects in Al-doped ZnO Films Grown by High-Speed Atmospheric Atomic Layer Deposition.

In this study, aluminum-doped zinc oxide (Al:ZnO) thin films were grown by high-speed atmospheric atomic layer deposition (AALD), and the effects of air annealing on film properties are investigated. The experimental results show that the thermal annealing can significantly reduce the amount of oxygen vacancies defects as evidenced by X-ray photoelectron spectroscopy spectra due to the in-diffusion of oxygen from air to the films. As shown by X-ray diffraction, the annealing repairs the crystalline structure and releases the stress. The absorption coefficient of the films increases with the annealing temperature due to the increased density. The annealing temperature reaching 600 °C leads to relatively significant changes in grain size and band gap. From the results of band gap and Hall-effect measurements, the annealing temperature lower than 600 °C reduces the oxygen vacancies defects acting as shallow donors, while it is suspected that the annealing temperature higher than 600 °C can further remove the oxygen defects introduced mid-gap states.

[Novel role of intracellular ATP in obesity pathology].

ATP is an important energy source for cells. Traditionally, intracellular ATP levels are believed to be relatively stable and will not rise consistently in the physiological conditions. However, new studies suggest that ATP levels may rise in multiple tissues under the condition of energy surplus contributing to the metabolic disorders in obesity. However, the molecular mechanism of ATP elevation remains unknown in obesity except the increase in energy supply. Based on our experimental results and the findings reported in the literature, we discuss the cellular and molecular mechanisms by which ATP levels are regulated in cells by multiple factors, including superoxide ions, mitochondrial flash, antioxidants, anti-apoptotic molecule Bcl-xL, AMP-activated protein kinase (AMPK) and metformin. Contribution of these factors to the alteration of ATP set-point will be discussed together with their impact on insulin resistance in type 2 diabetes mellitus. With a focus on the energy surplus in obesity, we explore the mechanism of insulin resistance induced by ATP elevation and provide an answer to the contradiction between the new experimental results and the traditional viewpoint of intracellular ATP. We propose that elevation of intracellular ATP may lead to metabolic disorder in obesity through activation of a feedback mechanism that inhibits mitochondrial function.

Diverse Structures Based on a Heptanuclear Cobalt Cluster with 0D to 3D Metal-Organic Frameworks: Magnetism and Application in Batteries.

Polymetallic complexes with interesting multifunctions have attracted extensive investigation. Synthesized through the use of different cobalt salt anions and solvents, five complexes, namely [CoII4 CoIII3 (H2 L)3 Cl5 (MeOH)] (1), [CoII4 CoIII3 (H2 L)3 (CH3 COO)4 (HCOO)⋅H2 O]n (2), [CoII4 CoIII3 (H2 L)3 (HCOO)4 (NO3 )⋅2H2 O]n (3), [CoII4 CoIII3 (H2 L)3 (bda)(CH3 COO)4 ⋅2H2 O]n (4), and [CoII4 CoIII3 (H2 L)3 (ipa)(HCOO)3 (dmf)⋅H2 O]n (5) (H6 L=bis-tris propane; BDA=biphenyl-4,4'-dicarboxylic acid; IPA=isophthalic acid; DMF=N,N-dimethylformamide), based on the heptanuclear {CoII4 CoIII3 } cluster with structures from 0D to 3D metal-organic frameworks (MOFs) have been solvothermally synthesized. Compound 1 is the first 0D heptanuclear cluster based on H6 L. Compound 2 crystallizes in the chiral space group P21 21 21 and consists of a 1D chiral helical chain. Complex 3 exhibits a 3D network structure. Compound 4 possesses a 1D zigzag-like chain structure. Finally, compound 5 was obtained as a 3D microporous structure. Compounds 1, 3, and 4 display dominant ferrimagnetic interactions whereas compounds 2 and 5 exhibit antiferromagnetic interactions. Moreover, the Co3 O4 prepared by calcining compound 2 presents a reversible capacity of 1122.9 mA h g-1 at 0.2 A g-1 after 100 cycles and an excellent rate capability, which suggests that coordination compounds with a 1D chain structure are outstanding precursors for preparing anode materials for lithium ion batteries.

Star-Like CBe5Au5+ Cluster: Planar Pentacoordinate Carbon, Superalkali Cation, and Multifold (π and σ) Aromaticity.

We report on the computational design of star-like CBe5Au5+ cluster with planar pentacoordinate carbon (ppC), which is also classified as a superalkali cation. Relevant isovalent CBe5Aunn-4 (n = 2-4), BBe5Au5, and NBe5Au52+ clusters with ppC/B/N are studied as well. Global-minimum structures of the clusters are established via computer global searches. The species feature a pentacoordinate pentagonal XBe5 (X = C, B, N) core, with Au occupying outer bridging positions. Molecular dynamics simulations indicate that they are dynamically stable. Bonding analysis reveals 3-fold (π and σ) aromaticity in CBe5Au5+, a key concept that overrides the 18-electron rule and should be applicable for (or help revisit existing models of) other planar hypercoordinate systems. Vertical electron affinities of CBe5Au5+ and its lighter counterparts (CBe5Cu5+ and CBe5Ag5+) are calculated to be unusually low, which are below 3.89 eV, the smallest atomic ionization potential of any element in the periodic table. Thus, these three clusters belong to superalkali cations. The merge of ppC and superalkali characters makes them unique chemical species.