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Abstract: Taiwan experienced a large number of severe acute respiratory syndrome (SARS) viral infections between March and July 2003; by September of that year, 346 SARS cases were confirmed by RT-PCR or serological tests. In order to better understand evolutionary relationships among SARS coronaviruses (SCoVs) from different international regions, we performed phylogenetic comparisons of full-length genomic and protein sequences from 45 human SCoVs (including 12 from Taiwan) and two civet SCoVs. All the Taiwanese SARS-CoV strains which associated with nosocomial infection formed a monophyletic clade within the late phase of the SARS epidemic. This Taiwanese clade could be further divided into two epidemic waves. Taiwan SCoVs in the first wave clustered with three isolates from the Amoy Gardens housing complex in Hong Kong indicating their possible origin. Of the 45 human SCoVs, one isolate from Guangdong province, China, exhibited an extra 29-nucleotide fragment between Orf 10 and Orf 11—similar to the civet SCoV genome. Nucleotide and protein sequence comparisons suggested that all SCoVs of late epidemic came from human-to-human transmission, while certain SCoVs of early epidemic might have originated in animals. [Copyright &y& Elsevier]

Cleft lip and palate (CL/P) is a common disfiguring birth defect with complex, poorly understood etiology. Mice carrying a spontaneous mutation, Dancer (Dc), exhibit CL/P in homozygotes and show significantly increased susceptibility to CL/P in heterozygotes [Deol, M. S. & Lane, P. W. (1966) J. Embryol. Exp. Morphol. 16, 543-558 and Trasler, D. G., Kemp, D. & Trasler, T. A. (1984) Teratology 29, 101-104], providing an animal model for understanding the molecular pathogenesis of CL/P. We genetically mapped Dc to within a 1-cM region near the centromere of chromosome 19. In situ hybridization analysis showed that one positional candidate gene, Tbx10, is ectopically expressed in Dc mutant embryos. Positional cloning of the Dc locus revealed an insertion of a 3.3-kb sequence containing the 5' region of the p23 gene into the first intron of Tbx10, which causes ectopic expression of a p23-Tbx10 chimeric transcript encoding a protein product identical to a normal variant of the Tbx10 protein. Furthermore, we show that ectopic expression of Tbx10 in transgenic mice recapitulates the Dc mutant phenotype, indicating that CL/P in Dc mutant mice results from the p23 insertion-induced ectopic Tbx10 expression. These results identify gain of function of a T-box transcription factor gene as a mechanism underlying CL/P pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Osteoprotegerin (OPG) is supposed to participate in the development of atherosclerosis and cardio-cerebrovascular disease. However, the results of research on relationship between OPG and ischemic stroke (IS) are controversial. Therefore, we carried out the first systematic review and meta-analysis to evaluate prognostic effect of osteoprotegerin in patients with IS. Methods: We comprehensively searched databases of PubMed, Embase, and the Cochrane Library through 21 August 2023 to identify observational studies that evaluated effect of OPG on poor functional outcome (modified Rankin Scale [mRS] Score of 3–6) and mortality in patients with IS. Adjusted odds ratios (aOR) with a 95% confidence interval (CI) of each included study were used as much as possible to assess the pooled effect. Results: Five studies that enrolled 4,506 patients in total fulfilled our inclusion criteria. Three studies were included in the pooled analysis for each endpoint since one of the included studies had provided data on poor functional outcome as well as mortality. OPG was neither associated with poor functional outcome (aOR 1.29, 95% CI 0.90–1.85) nor with mortality (aOR 1.57, 95% CI 0.90–2.74) in patients with IS. Conclusions: There is insufficient evidence to demonstrate the correlation between OPG and mortality or poor functional outcome in IS patients. OPG cannot be applied to predict worse neurological function in IS patients based on the current evidence. [ABSTRACT FROM AUTHOR]

An efficient and broadly applicable rhodium‐catalyzed direct ortho‐arylation of anilines with aryl iodides relying on readily available aminophosphines as traceless directing groups is reported. Its scope and functional group compatibility were both found to be quite broad as a large variety of both aminophosphines and (hetero)aryl iodides, including complex ones, could be utilized. The ortho‐arylated anilines could be obtained in high average yields, without any competing diarylation and with full regioselectivity, which constitutes a major step forward compared to other processes. The reaction is moreover not limited to aryl iodides, as an aryl bromide and a triflate could be successfully used, and could be extended to diarylation. Mechanistic studies revealed the key and unique role of the aminophosphine, acting not only as a substrate but also as a ligand for the rhodium catalyst. [ABSTRACT FROM AUTHOR]

Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method. [ABSTRACT FROM AUTHOR]

Geminal bis(boronates) are versatile synthetic building blocks in organic chemistry. The fact that they predominantly serve as nucleophiles in the previous reports, however, has restrained their synthetic potential. Herein we disclose the ambiphilic reactivity of α‐halogenated geminal bis(boronates), of which the first catalytic utilization was accomplished by merging a formal Heck cross‐coupling with a highly diastereoselective allylboration of aldehydes or imines, providing a new avenue for rapid assembly of polyfunctionalized boron‐containing compounds. We demonstrated that this cascade reaction is highly efficient and compatible with various functional groups, and a wide range of heterocycles. In contrast to a classical Pd(0/II) scenario, mechanistic experiments and DFT calculations have provided strong evidence for a catalytic cycle involving Pd(I)/diboryl carbon radical intermediates. [ABSTRACT FROM AUTHOR]

Geminal bis(boronates) are versatile synthetic building blocks in organic chemistry. The fact that they predominantly serve as nucleophiles in the previous reports, however, has restrained their synthetic potential. Herein we disclose the ambiphilic reactivity of α‐halogenated geminal bis(boronates), of which the first catalytic utilization was accomplished by merging a formal Heck cross‐coupling with a highly diastereoselective allylboration of aldehydes or imines, providing a new avenue for rapid assembly of polyfunctionalized boron‐containing compounds. We demonstrated that this cascade reaction is highly efficient and compatible with various functional groups, and a wide range of heterocycles. In contrast to a classical Pd(0/II) scenario, mechanistic experiments and DFT calculations have provided strong evidence for a catalytic cycle involving Pd(I)/diboryl carbon radical intermediates. [ABSTRACT FROM AUTHOR]

Biochar application can alleviate the adverse effects of saline-alkali stress on crops. However, the long-term effects of one-off biochar application on soil physicochemical properties, salt concentration, nutrient availability, soil enzyme activities, and rice yield under highly saline-alkali paddy soils remain unclear. Here, a 6-year paddy field study was conducted in a saline-alkali paddy field using two nitrogen application levels (0 and 225 kg ha−1) and four biochar application rates [0 (T0), 1.5% (T1.5), 3.0% (T3.0), and 4.5% (T4.5) biochar, w/w]. The results showed that compared with T0, the bulk density (BD) under T1.5, T3.0, and T4.5 treatments significantly decreased by 11.21%, 16.33%, and 25.57%, while total porosity (Tp) and saturated hydraulic conductivity (Ks) increased by 19.15–27.34% and 3217.78–5539.83%, respectively. Biochar consistently improved soil macro-aggregates, mean weight diameter (MWD), and the percentage of water-stable aggregates (PWSA) over the years. Additionally, one-off application of biochar continuously reduced the soil Na+ concentration, Na+/K+ ratio, Na+/Ca2+ ratio, saturated paste extract (ECe), exchangeable sodium percentage (ESP), and sodium adsorption ratio (SARe). However, it reduced the pH in 2021 and 2022 only. It enhanced the concentration of K+, Ca2+, Mg2+, and cation exchange capacity (CEC) over the 6-year study, indicating its longer-term positive impact. Furthermore, the one-off biochar application, especially under high application rate treatments (T3.0 and T4.5), significantly and continuously improved nutrient availability and soil enzyme activities. However, alkali-hydrolysable nitrogen (AN) decreased in the initial year of biochar application. The grain yield of T1.5, T3.0, and T4.5 surpassed that of T0 by 116.38%, 141.24%, and 145.20%, respectively. Notably, the rice yield reached its peak with the treatment of 3.0% (w/w) in all 6 years of study period. These findings offered new perspectives on repairing and improving soil quality and production ability of highly saline-alkali paddy soils. Highlights: A long-term (6-year), one-off application of biochar was conducted in a highly saline-alkali paddy field. Biochar consistently decreased soil BD, increased Tp, Ks, and improved soil aggregates. Biochar showed a sustained ability to alleviate saline-alkali stress. The continuous improvement of soil functions acted on the increase of rice yield. [ABSTRACT FROM AUTHOR]

Summary: Black wolfberry (Lycium ruthenicum Murr.) contains various bioactive metabolites represented by flavonoids, which are quite different among production regions. However, the underlying regulation mechanism of flavonoid biosynthesis governing the bioactivity of black wolfberry remains unclear.Presently, we compared the bioactivity of black wolfberry from five production regions. Multi‐omics were performed to construct the regulation network associated with the fruit bioactivity. The detailed regulation mechanisms were identified using genetic and molecular methods.Typically, Qinghai (QH) fruit exhibited higher antioxidant and anti‐inflammatory activities. The higher medicinal activity of QH fruit was closely associated with the accumulation of eight flavonoids, especially Kaempferol‐3‐O‐rutinoside (K3R) and Quercetin‐3‐O‐rutinoside (rutin). Flavonoid biosynthesis was found to be more active in QH fruit, and the upregulation of LrFLS, LrCHS, LrF3H and LrCYP75B1 caused the accumulation of K3R and rutin, leading to high medicinal bioactivities of black wolfberry. Importantly, transcription factor LrMYB94 was found to regulate LrFLS, LrCHS and LrF3H, while LrWRKY32 directly triggered LrCYP75B1 expression. Moreover, LrMYB94 interacted with LrWRKY32 to promote LrWRKY32‐regulated LrCYP75B1 expression and rutin synthesis in black wolfberry. Transgenic black wolfberry overexpressing LrMYB94/LrWRKY32 contained higher levels of K3R and rutin, and exhibited high medicinal bioactivities. Importantly, the LrMYB94/LrWRKY32‐regulated flavonoid biosynthesis was light‐responsive, showing the importance of light intensity for the medicinal quality of black wolfberry.Overall, our results elucidated the regulation mechanisms of K3R and rutin synthesis, providing the basis for the genetic breeding of high‐quality black wolfberry. [ABSTRACT FROM AUTHOR]

REFERENCES 1 Zhang L., Yu L., Wang Q., Zhang Y., Si X. Application of Minocycline-Containing Bismuth Quadruple Therapies as First-Line Regimens in the Treatment of Helicobacter pylori. In the article titled "Application of Minocycline-Containing Bismuth Quadruple Therapies as First-Line Regimens in the Treatment of Helicobacter pylori" [[1]], there was an error in Subjects and Methods. [Extracted from the article]

RNA modification is an important form of regulation in cancer biology, that is capable of affecting cell proliferation, migration, other genetic characteristics of tumors, and protein expression. Recent research has shown that dysregulation of RNA modification plays an important role in glioma pathogenesis. A key form of RNA post-transcriptional modification, alternative polyadenylation (APA), may represent a mechanism by which genes escape miRNA-mediated inhibition of cancer. Global shortening of 3' untranslated region (3'-UTR)-mediated APA events have become a potential novel marker of cancer progression. Current treatments in which a single gene or pathway is targeted do not have significant therapeutic benefits for glioma patients, while strategies that are less targeted, in which inhibitors of major regulatory hubs such as APA regulators are utilized, may have superior therapeutic effects. However, the precise mechanisms by which untranslated region-alternative polyadenylation (UTR-APA) regulates glioma are poorly understood. In the present review, we will discuss the important roles of UTR-APA in glioma. In addition to the role of APA in the progression of glioma, we will also explore potential treatment options that target these processes to improve the prognosis of glioma patients. [Display omitted] • UTR-APA exerts various important effects on the regulation of glioma progression. • Various factors could regulate APA and 3'UTR length in the brain. • UTR-APA exerts important effects on various oncogenes during glioma tumorigenesis. • UTR-APA plays important roles in drug resistance in glioma treatment. [ABSTRACT FROM AUTHOR]

• The influence of excitation signal type on the transmission mechanism of head mass was disclosed. • The vibration performance of head masses under resonate state was quantitative estimation. • The selection principle of head mass based on excitation signal type was summarized. The head mass as front-end material is an essential component of Tonpilz transducers. The transmission mechanism of head mass under excitations of continuous wave and short pulse are investigated in order to maximize the transducer acoustic radiation power. In the case of continuous wave excitation, it was found that the role of the head mass is to change the effective vibration velocity, and the transmitting voltage response is proportional to the characteristic impedance of the head mass. In the case of short pulse excitation, the head mass acts as a medium layer, and the highest acoustic radiation power appears when the characteristic acoustic impedance of head mass matches that of water medium. Our results provide deeper insight on the Tonpilz transducer design mechanism, and useful selection rules for the front-end material under different types of excitation signals. [ABSTRACT FROM AUTHOR]

The performance of an X‐band flexible band‐filter on ultra‐thin liquid crystal polymer (LCP) substrate is investigated. The 50 µm‐thick LCP substrate is adopted to enhance the flexibility of circuits. For the purpose of fabrication by the conventional printed circuit board process, copper‐clad laminate with 18 µm thickness is selected. Excellent microwave transmission characterisation is demonstrated by measuring the microstrip line at flat and bending conditions. An X‐band interdigital bandpass filter based on a half‐wavelength microstrip line resonator is designed and fabricated for purpose of demonstration. The measured results at the flat condition show that the insertion loss is 2.1 dB at centre frequency of 9.4 GHz and the return loss is better than 20 dB at the designed band. The performance at the bending condition shows that the bending effect causes little deterioration to the performance at a different bending radius. [ABSTRACT FROM AUTHOR]

The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct. Previous results suggest that determination of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition. These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates. Here we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2, are expressed in alternating cell types in the developing sensory epithelium. In addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear mosaic. [ABSTRACT FROM AUTHOR]

During each pandemic in human history, cities have become the centers of the disasters that have unfolded. The main reason is that cities develop unevenly. Some favorable factors promoting city development are also important factors that facilitate the spread of viruses; the urbanization development path that tends toward polarized development greatly increases the risk of central cities becoming epicenters of disaster. This article will take the Wuhan urban agglomeration as an example to explore the reasons for weak points of urban agglomerations in the context of COVID-19, and will then examine their new development, new directions, new modes, and future. This has extremely important practical value and strategic significance for the high-quality development of China and for the future transformation of the world's urban civilization. [ABSTRACT FROM AUTHOR]

Dielectric materials with a high recoverable energy-storage density (W rec) and an enhanced power density are required for downsizing pulsed power electronic devices. Dielectrics with a low but temperature-stable permittivity are better suited as energy-storage materials for power devices owing to their delayed saturation polarization response. ABO 3 perovskite-structured (Bi 0. 5 Na 0.5)TiO 3 -based [(Bi 0. 5 Na 0.5) 0.93 Ca 0.07 ](Ti 0. 85 Zr 0.15)O 3 (BCZ) lead-free ceramics exhibit good dielectric temperature stability and are being investigated as viable materials for energy-storage devices. However, these materials only produced limited W rec due to the reduced breakdown strength (BDS). Herein, various advanced engineering techniques, including glass doping and the viscous polymer rolling process, were applied to the BCZ to substantially enhance the BDS of the ceramics. Our results show that the BCZ-0.75 wt% glass-additive composition achieved an ultrahigh W rec of 7.78 J/cm3 under a comparatively low electric field and remained above 4.6 J/cm3 in the temperature range of 30 °C–160 °C. This work demonstrates that the BCZ is a viable competitor for lead-free dielectrics and guides for the development of novel high-performance dielectric materials for future pulsed power devices. [ABSTRACT FROM AUTHOR]

The study was to explore the effect of different levels of clove and Sophora japonica extracts on production performance, slaughter performance, meat quality and cecal bacteria of Sanhuang chickens. A total of 256 45-day-old broilers were randomly divided into four groups, with four replicates in each group and 16 broilers in each replicate. Broilers in control group (group I) were fed with a basal diet, and broilers in group II, group III and group IV were fed with a basal diet supplemented with 150, 200 and 300 mg/kg clove and Sophora japonica extracts, respectively. The pre- feeding period was 5 d, and the test period was 70 d. The results showed that compared with group I, the average daily feed intake and average daily gain of Sanhuang chickens in group II, group III and IV were significantly increased, the feed to gain ratio was significantly decreased (P<0.05). The chest muscle rate and lean meat rate of Sanhuang chickens in group III were significantly higher than those in group I, group IV (P<0.05), the leg muscle rate of Sanhuang chickens in group III was significantly higher than that in group I (P<0.05), and the abdominal fat rate was significantly lower (P<0.05). The OD value of pectoral muscle color of Sanhuang chickens in group I was significantly higher than that in group I, group II (P<0.05), the drip loss of pectoral and leg muscles of Sanhuang chickens in group II, group III was significantly lower than that in group I, group IV (P<0.05), the pH45 min value and pH24h value of pectoral muscle and pH45min value and pH24h value of leg muscle of Sanhuang chickens in group III were significantly higher than those in group I (P<0.05). Compared with group I, the content of intestinal Bacteroidetes in group II, group III and group IV increased in varying degrees, the content of Firmicutes in group II, group IV was higher than that in group I (P>0.05). The experiment indicates that clove and Sophora japonica extract can effectively improve the growth performance of Sanhuang chicken, help to maintain the stability of cecal bacterial population, which has a positive impact on intestinal health. The best feeding effect is supplementing 200 mg/kg diet. [ABSTRACT FROM AUTHOR]

Provides information on a study on the effects of changes in calorie intake on intestinal nutrient uptake and transporter mRNA levels in aged mice. Materials used in the study; Methodology; Results of the study; Discussion of the study.

Phytochemical investigation of Cajanus scarabaeoides (L.) Thouars (Fabaceae) led to the isolation of six compounds. The chemical structures of all compounds were determined by spectroscopic methods. All isolates were reported from this species for the first time. The presence of these compounds is consistent with the chemical classes reported from other members of the genus Cajanus. In summary, this study reported six compounds isolated from Cajanus scarabaeoides and discussed the plant chemotaxonomy of Cajanus genus. • Six compounds (1 – 6) were first isolated from C. scarabaeoides. • It is the first report of isolation of compounds 3 and 6 from the genus Cajanus. • This is the first chemical investigation of C. scarabaeoides. • These compounds provide evidence for chemotaxonomic studies of C. scarabaeoides and the genus Cajanus. [ABSTRACT FROM AUTHOR]

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12944-020-01416-2 [ABSTRACT FROM AUTHOR]

BCL-2, a key protein in inhibiting apoptosis, has a 65-residue-long highly flexible loop domain (FLD) located on the opposite side of its ligand-binding groove. In vivo phosphorylation of the FLD enhances the affinity of BCL-2 for pro-apoptotic ligands, and consequently anti-apoptotic activity. However, it remains unknown as to how the faraway, unstructured FLD modulates the affinity. Here we investigate the protein-ligand interactions by fluorescence techniques and monitor protein dynamics by DEER and NMR spectroscopy tools. We show that phosphomimetic mutations on the FLD lead to a reduction in structural flexibility, hence promoting ligand access to the groove. The bound pro-apoptotic ligands can be displaced by the BCL-2-selective inhibitor ABT-199 efficiently, and thus released to trigger apoptosis. We show that changes in structural flexibility on an unstructured loop can activate an allosteric protein that is otherwise structurally inactive. Lan et al. make single and triple phosphomimetic mutations in a long flexible loop domain of BCL-2 and show that these mutations reduce structural flexibility and promote ligand access to the groove. Their study indicates that changes in structural flexibility on an unstructured loop can activate an allosteric, otherwise inactive protein. [ABSTRACT FROM AUTHOR]

In this study, we aimed to develop a multifunctional drug/gene delivery system for the treatment of glioblastoma multiforme by combining the ligand-mediated active targeting and the pH-triggered drug release features of graphene oxide (GO). Toward this end, we load irinotecan (CPT-11) to cetuximab (CET)-conjugated GO (GO-CET/CPT11) for pH-responsive drug release after endocytosis by epidermal growth factor receptor (EGFR) over-expressed U87 human glioblastoma cells. The ultimate injectable drug/gene delivery system was designed by co-entrapping stomatin-like protein 2 (SLP2) short hairpin RNA (shRNA) and GO-CET/CPT11 in thermosensitive chitosan-g-poly(N-isopropylacrylamide) (CPN) polymer solution, which offers a hydrogel depot for localized, sustained delivery of the therapeutics after the in situ formation of CPN@GO-CET/CPT11@shRNA hydrogel. An optimal drug formulation was achieved by considering both the loading efficiency and loading content of CPT-11 on GO-CET. A sustained and controlled release behavior was found for CPT-11 and shRNA from CPN hydrogel. Confocal microscopy analysis confirmed the intracellular trafficking for the targeted delivery of CPT-11 through interactions of CET with EGFR on the U87 cell surface. The efficient transfection of U87 using SLP2 shRNA was achieved using CPN as a delivery milieu, possibly by the formation of shRNA/CPN polyplex after hydrogel degradation. In vitro cell culture experiments confirmed cell apoptosis induced by CPT-11 released from acid organelles in the cytoplasm by flow cytometry, as well as reduced SLP2 protein expression and inhibited cell migration due to gene silencing. Finally, in vivo therapeutic efficacy was demonstrated using the xenograft of U87 tumor-bearing nude mice through non-invasive intratumoral delivery of CPN@GO-CET/CPT11@shRNA by injection. Overall, we have demonstrated the novelty of this thermosensitive hydrogel to be an excellent depot for the co-delivery of anticancer drugs and siRNA. The in situ forming hydrogel will not only provide extended drug release but also combine the advantages offered by the chitosan-based copolymer structure for siRNA delivery to broaden treatment modalities in cancer therapy. [ABSTRACT FROM AUTHOR]

Conventional flextensional transducers possess advantages of low frequency, small dimension, and high power [K. D. Rolt, J. Acoust. Soc. Am. 87, 1340 (1990)]. The low-frequency circular array composed of flextensional transducers has a strong mutual radiation effect due to the large vibration amplitude of the radiation surface located inside the circular array and the close distance between array elements [Z. Y. He et al., AIP Conf. Proc. 1272, 345 (2010)]. Here, a single-sided radiation flextensional transducer (SSR FT) is designed for a low-frequency circular close-packed array to diminish the mutual radiation effect. On the basis of the vibration principle of SSR FT, effects of structural parameters on electroacoustic, vibration, and radiation performance are studied for the final design of the transducer. Subsequently, the mutual radiation effect of circular close-packed arrays composed of SSR FTs and their counterparts is qualitatively analyzed on the basis of resonant mass, equivalent circuit, and numerical simulations. Finally, fabricated and tested circular arrays lead to a conclusion that the circular array composed of SSR FTs has a weaker mutual radiation effect and smaller dimensions than its counterpart composed of class IV FTs [K. P. B. Moosad, G. Chandrashekar, M. J. Joseph, and R. John, Appl. Acoust. 72, 127–131 (2011)]. The results confirm that the circular close-packed array provides flexibility in the application of low-frequency and small-dimension underwater acoustic sources. [ABSTRACT FROM AUTHOR]

• The hot spots connected by the scattering wave vectors q i construct an octet scattering model. • The quasiparticle excitation spectrum is split into its bonding and antibonding components due to the presence of the bilayer coupling. • The peak-dip-hump structure in the quasiparticle excitation spectrum along the Fermi surface is related with the peak-structure in the quasiparticle scattering rate except for at hot spots, where it is caused by the bilayer coupling. • The kink in the quasiparticle dispersion is present all around the Fermi surface. • The characteristic features of the renormalization of the electrons are particularly obvious due to the presence of the bilayer coupling. Cuprate superconductors have a layered structure, and then the physical properties are significantly enriched when two or more two copper-oxide layers are contained in a unit cell. Here the characteristic features of the renormalization of the electrons in the bilayer cuprate superconductors are investigated within the framework of the kinetic-energy driven superconducting mechanism. It is shown that the electron quasiparticle excitation spectrum is split into its bonding and antibonding components due to the presence of the bilayer coupling, with each component that is independent. However, in the underdoped and optimally doped regimes, although the bonding and antibonding electron Fermi surface contours deriving from the bonding and antibonding layers are truncated to form the disconnected bonding and antibonding Fermi arcs, almost all spectral weights in the bonding and antibonding Fermi arcs are reduced to the tips of the bonding and antibonding Fermi arcs, which in this case coincide with the bonding and antibonding hot spots. These hot spots connected by the scattering wave vectors q i construct an octet scattering model, and then the enhancement of the quasiparticle scattering processes with the scattering wave vectors q i is confirmed via the result of the autocorrelation of the electron quasiparticle excitation spectral intensities. Moreover, the peak-dip-hump structure developed in each component of the electron quasiparticle excitation spectrum along the corresponding electron Fermi surface is directly related with the peak structure in the quasiparticle scattering rate except for at around the hot spots, where the peak-dip-hump structure is caused mainly by the pure bilayer coupling. Although the kink in the electron quasiparticle dispersion is present all around the electron Fermi surface, when the momentum moves away from the node to the antinode, the kink energy smoothly decreases, while the dispersion kink becomes more pronounced, and in particular, near the cut close to the antinode, develops into a break separating of the fasting dispersing high-energy part of the electron quasiparticle excitation spectrum from the slower dispersing low-energy part. By comparing with the corresponding results in the single-layer case, the theory also indicates that the characteristic features of the renormalization of the electrons are particularly obvious due to the presence of the bilayer coupling. [ABSTRACT FROM AUTHOR]

Abstract: Within the kinetic energy driven superconductivity, the electron spectrum of bilayer cuprate superconductors is studied. It is shown that the electron spectrum of bilayer cuprate superconductors is split into the bonding and antibonding components by the bilayer splitting, then the main features of the peak–dip–hump structure in the point of the Brillouin zone are caused by the bilayer splitting, with the peak and hump corresponding to the antibonding and bonding bands, respectively. [Copyright &y& Elsevier]

Ginseng (Panax ginseng Meyer) has long been consumed as a medicinal or functional food in East Asia. It is available as dried white ginseng (WG) and steamed red ginseng (RG), which might differ in ginsenoside profiles. We compared ginsenoside types of RG and WG using UPLC‐MS/MS and evaluated how they biologically affected heart of healthy rats by recording electrocardiography, measuring biochemical indicators, analyzing cardiac tissue slides, and Ca2+ signaling pathways. About 25 and 29 ginsenosides were detected in WG and RG, respectively, and the total ginsenoside content of RG contained was nearly 1.8 times higher than that of WG. Among them, ginsenoside Rg4, ginsenoside Rg6, ginsenoside Rh4, ginsenoside Rk1, ginsenoside Rg5, and protopanaxadiol were detected only in RG, while 20(R)‐ginsenoside Rg2 was detected only in WG. Male SD rats treated by intraperitoneal injection of WG or RG extracts were similar to the control in terms of electrocardiography and heart histology, indicating that both may not significantly affect the rats' myocardial function. However, WG and RG may induce mild cardiac injury resulting in increased cardiac collagen and creatine kinase levels. In addition, upregulated p‐CaMKII and PPARδ and downregulated SERCA2a for WG and RG treatments were further associated with increased cardiac contractility. In general, RG had less effect on the heart of healthy rats than WG, which may be due to RG having a high proportion of low‐polar ginsenosides. [ABSTRACT FROM AUTHOR]

Due to their elevated sintering temperature, pure PLZST-based antiferroelectric ceramics are unsuitable for co-firing with copper internal electrodes as MLCC dielectric materials. In this work, PLZST ceramic materials sintered at low temperature in reducing atmosphere were obtained through a unique BASK glass additive and Y3+ co-doping. While the sintering temperature of ceramics is reduced to 1040 °C, stable defect association ( Y Pb ∙ , Y Zr ′ ) is formed by Y3+ solution entering A/B site, which effectively inhibits the increase of defect concentration and promotes ceramic sintering. The high breakdown strength of PLSZT ceramics is attributed to their compact grain and excellent insulation resistivity, which enhance their tolerance to electric fields. An ultrahigh recoverable energy density (W rec) of 4.9 J/cm3 with a high energy storage efficiency (η) of 92.8% are achieved at an electric field of 400 kV/cm. Moreover, the AFE ceramics possess excellent discharge energy storage properties with a high discharge energy density (W d) of 4.4 J/cm3 and a large power density (P d) of 125 MW/cm3. [ABSTRACT FROM AUTHOR]

Boronate rearrangements, such as the Matteson and Petasis reactions, are valuable metal‐free reactions for the transfer of the carbo group on boron to intramolecular electrophilic sites. However, only highly reactive electrophiles are suitable, and ketones are too inactive for those boronate rearrangements due to the high energy barriers. We disclose here the 1,3‐boronate rearrangement to ketones, for which a high energy barrier (44.9 kcal/mol) is prohibitory for thermal reactions in the ground state. The reaction is enabled by the key keto‐enol‐boronate bidentate complex formation in situ, which absorbs visible light to reach the excited state for the chemoselective 1,3‐boronate rearrangement to ketones. Experimental and computational investigations exclude free radical intermediates from organoboronates. The aryl, alkenyl, and alkyl boronic acids react with various 1,3‐diketones driven by visible light irradiation to construct structurally diverse β‐keto tertiary alcohols under metal‐free conditions. The reaction demonstrates substrate diversity with 58 examples, yields up to 98 %, and it is suitable for gram‐scale synthesis. [ABSTRACT FROM AUTHOR]

Boronate rearrangements, such as the Matteson and Petasis reactions, are valuable metal‐free reactions for the transfer of the carbo group on boron to intramolecular electrophilic sites. However, only highly reactive electrophiles are suitable, and ketones are too inactive for those boronate rearrangements due to the high energy barriers. We disclose here the 1,3‐boronate rearrangement to ketones, for which a high energy barrier (44.9 kcal/mol) is prohibitory for thermal reactions in the ground state. The reaction is enabled by the key keto‐enol‐boronate bidentate complex formation in situ, which absorbs visible light to reach the excited state for the chemoselective 1,3‐boronate rearrangement to ketones. Experimental and computational investigations exclude free radical intermediates from organoboronates. The aryl, alkenyl, and alkyl boronic acids react with various 1,3‐diketones driven by visible light irradiation to construct structurally diverse β‐keto tertiary alcohols under metal‐free conditions. The reaction demonstrates substrate diversity with 58 examples, yields up to 98 %, and it is suitable for gram‐scale synthesis. [ABSTRACT FROM AUTHOR]

Dianhong Black Tea, a fermented tea containing various bioactive ingredients, has been found to have a significant role in alleviating alcoholic liver injury (ALI). One of its main unique components, Dianhong Black Tea volatile substances (DBTVS), may have potential anti‐ALI effects. However, its effects and underlying molecular mechanisms are still unknown. In this study, we aimed to investigate the potential of DBTVS as an anti‐ALI agent using alcohol‐fed rats. We assessed the effect of DBTVS on ALI by analyzing serum transaminase and lipid levels, as well as conducting hematoxylin–eosin and oil red O staining. Additionally, GC‐MS was used to detect the components of DBTVS, while transcriptome, proteomics analysis, Western blot, and molecular docking were employed to uncover the underlying mechanisms. Our results demonstrated that DBTVS significantly reduced serum ALT and AST levels and improved lipid metabolism disorders. Moreover, we identified 14 components in DBTVS, with five of them exhibiting strong binding affinity with key proteins. These findings suggested that DBTVS could be a promising agent for the prevention and treatment of ALI. Its potential therapeutic effects may be attributed to its ability to regulate lipid metabolism through the PPAR signaling pathway. [ABSTRACT FROM AUTHOR]

Nitrogen doped ordered mesoporous carbon (NOMC) was prepared using SBA-15 as a hard template agent and solvent evaporation induced self-assembly of coal based asphaltene with polyacryloni-trile (PAN). Further enhance the specific surface area and capacitance performance of NOMC through CO2 activation. The results showed that when the ratio of SBA-15, asphaltene and PAN was 1:1.2:4.8, the carbonization rate and orderliness of the carbon material obtained at 800 °C were higher. After activation at 900 °C, the specific surface area, pore volume, and pore size were 602.1 m²/g, 0.426 cm³/g, 3.808 nm, respectively, and the specific capacitance reached 127.2 F/g, which was 41.8% higher than that of unactivation. [ABSTRACT FROM AUTHOR]

BAX activation is a crucial step for commitment to apoptosis. Several activators, such as BimBH3-based therapeutic peptides and cleaved Bid (cBid) protein, can trigger BAX-mediated apoptosis, but it is unclear whether they proceed through the same pathway. Here we utilize PEGylation-based approach, which is shown to efficiently shield individual binding grooves in BAX from activators, to investigate and reveal that the activators take different routes to induce BAX-mediated apoptosis. Various spectroscopic/biochemical tools, including electron spin resonance, circular dichroism, fluorescence recovery after photobleaching, and label-transfer assay, were employed to reveal details in the processes. We observe a key mutant BAX 164-PEG that acts differently in response to cBid and BimBH3 stimuli. While BimBH3 directly interacts with the trigger groove (TG) to induce the conformational changes in BAX that includes the release of α9 from the canonical groove (CG) and oligomerization, cBid engages with CG and works with mitochondrial lipids to fully activate BAX. PEGylation-based approach is proven useful to shield individual binding grooves of BAX from apoptotic stimuli. Groove engagement in CG of BAX is required for a full cBid-induced BAX activation. This study has identified differences in the pathways involved during the initiation of BAX activation by full-length cBid protein versus synthetic BimBH3-based peptides. Our finding is potentially valuable for therapeutic application as the pore-forming activity of 164-PEG is independent from the cBid-mediated apoptotic pathways, but can be administrated by the synthetic short peptides. Unlabelled Image • A full BAX activation for MOMP proceeds with two steps essentially. • Accessibility of trigger groove of BAX is required for initiation of activation. • BimBH3 peptide and cBid take different routes to activate BAX. • Cleaved Bid interacts with the canonical groove to promote BAX activation. • Accessibility of canonical groove is not strictly required for BAX activation. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the aerial parts of Euphorbia formosana Hayata resulted in the isolation of 33 compounds, including various derivatives of ellagic acid and gallic acid. The chemical structures were elucidated by spectroscopic methods and comparison with relevant data from the literature. The chemotaxonomic significance and distribution of these derivatives of ellagic acid and gallic acid in the genus Euphorbia are discussed. • Thirty-three compounds (1–33) were isolated from the aerial parts of Euphorbia formosana Hayata. • Seventeen compounds had never been found previously from this species. • These compounds provide evidence for chemotaxonomic studies of E. formosana and the genus Euphorbia. • Hydroquinone was first time reported from family Euphorbiaceae. [ABSTRACT FROM AUTHOR]

Objectives: Temozolomide (TMZ) is one of the most commonly used clinical drugs for glioblastoma (GBM) treatment, but its drug sensitivity needs to be improved. Gamabufotalin (CS‐6), the primary component of the traditional Chinese medicine "ChanSu," was shown to have strong anti‐cancer activity. However, more efforts should be directed towards reducing its toxicity or effective treatment doses. Methods: Target fishing experiment, Western blotting, PCR, confocal immunofluorescence and molecular cloning techniques were performed to search for possible downstream signalling pathways. In addition, GBM xenografts were used to further determine the potential molecular mechanisms of the synergistic effects of CS‐6 and TMZ in vivo. Results: Mechanistic research revealed a negative feedback loop between ATP1A3 and AQP4 through which CS‐6 inhibited GBM growth and mediated the synergistic treatment effect of CS‐6 and TMZ. In addition, by mutating potential amino acid residues of ATP1A3, which were predicted by modelling and docking to interact with CS‐6, we demonstrated that abrogating hydrogen bonding of the amino acid Thr794 interferes with the activation of ATP1A3 by CS‐6 and that the Thr794Ala mutation directly affects the synergistic treatment efficacy of CS‐6 and TMZ. Conclusions: As the main potential target of CS‐6, ATP1A3 activation critically depends on the hydrogen bonding of Thr794 with CS‐6. The combination of CS‐6 and TMZ could significantly reduce the therapeutic doses and promote the anti‐cancer efficacy of CS‐6/TMZ monotherapy. [ABSTRACT FROM AUTHOR]

• Novel approach to model turbulent thermal stresses in highly symmetrical geometries. • Application to triangular array rod bundles. • Full-height LES performed for the present project and presented for comparison. • Results are superior to available RANS and vastly cheaper than full scale LES. • Further speedup obtained with a novel Steady State solver in the SEM code Nek5000. An alternative methodology is proposed here to overcome the excessive cost of large eddy simulations (LES) of full-length heated rod bundle calculations, while improving the inaccurate results typically obtained with Reynolds-averaged Navier–Stokes equations (RANS). While the cost of the full-length LES is generally too high, LES of a small section of a single rod is usually affordable. The idea presented here consists of using the information granted by the small LES calculation to determine the appropriate turbulence viscosity or turbulent thermal diffusivity that can be used to solve only for the temperature field in a pseudo-RANS approach. The study has been performed with single-rod simulations with a P / D of 1.12 and 1.24, considering rod lengths that are representative of reactor applications, for the cases of uniform heat flux and a more realistic cosine-like axial heat distribution. The spectral element code Nek5000 has been used for all LES, RANS, and pseudo-RANS simulations. The recently proposed Nek5000 steady-state solver has been used for solving the temperature field in the pseudo-RANS approach and has proved significantly faster than transient schemes. Prediction of thermal quantities is compared with classical linear and nonlinear RANS models. LES for the full-length rods has also been performed and is used as a reference. Results of the proposed method show significant improvements with respect to those obtained with RANS. [ABSTRACT FROM AUTHOR]

In this work, the quasi-spherical β-Si3N4 powders were synthesized via an efficient direct nitridation strategy with CaF2 as the catalytic material under NH3 atmosphere. The effect of CaF2 on phase composition and crystalline morphology was studied. CaF2 additive can accelerate the nitridation of silicon powders, and the particles of nitridation products tend to have an equiaxed structure with the CaF2 additive increasing. When 4 wt% CaF2 additive or more was added, submicron β-Si3N4 particles with quasi-spherical morphology and eminent crystal integrity were obtained. In contrast, irregular α-Si3N4 particles appear as the main phase with less than 4 wt% CaF2 additive. The growth mechanism of Si3N4 particles was also discussed. CaxSiyOz liquid phase is crucial in the nitridation of silicon powders with CaF2 additive. [ABSTRACT FROM AUTHOR]

Most broadband Tonpilz transducers are achieved by coupling first-order longitudinal mode with other modes introduced by an elaborately designed structure (e.g., flexural mode of the head mass). To further expand the bandwidth is difficult and, even if successful, inevitably makes the structure more complex. Longitudinal modes are the inherent vibration modes of rod-shaped Tonpilz transducers. Using high-order longitudinal modes to achieve broadband performance can retain the simple structure similar to the conventional Tonpilz transducer. However, activating continuous, equal-amplitude longitudinal modes is not easy. The longitudinal length and position of the drive-stacks have significant influences on the generation of resonances and their vibration amplitude. In this paper, these influences are studied using the equivalent circuit method for a rod transducer having two drive-stacks, and finally we provide the drive-stack arrangement that can activate the first-three longitudinal modes to obtain the desired broadband response effectively. We also find that the response value of resonances can be balanced to reduce band fluctuation by adjusting drive lengths. The design procedure for the broadband Tonpilz transducer is proposed. The finite element method is used to design broadband transducers having bandwidth greater than one octave following the procedure. A transducer prototype with a simple structure is fabricated and measured to verify the validity of the proposed method. [ABSTRACT FROM AUTHOR]

In this paper, the two-layer 1–3 composite transducer using an unconventional part-excitation method is presented to achieve the ultra-wide operation band for the high-frequency underwater devices, in which the part-excitation refers to the method that only the lower-layer is excited, while the upper-layer in contact with the propagation medium is not excited. This method is first proposed by analyzing the longitudinal vibration modes of one piezoelectric rod in the 1–3 composite and finally, we conclude that if the excited lower-layer can be controlled to have thickness given by 3l/2n, where l is the whole thickness of the two-layer rod and n (n > 1) denotes the number of the coupled modes, then first n order modes can be activated simultaneously to form an ultra-wide operation band containing n response peaks. Finite element method (FEM) is employed to investigate the two-layer 1–3 composite with a thickness of 10 mm. The results show that when the thickness of the excited lower-layer is 3 mm (n = 5), the transducer attains the ultra-wideband by coupling five resonances, nearly covering the frequency range from 100 kHz to 1 MHz. According to the difference of response level, the whole band can be divided into multiple local wide bands. A prototype transducer is fabricated based on the FEM results, and the measured results show that the whole band contains three wide bands, covering the frequency ranges 125–295 kHz, 300–480 kHz, and 500–915 kHz, respectively. [ABSTRACT FROM AUTHOR]

As a lead-free material, AgNbO 3 has received a lot of attention for its potential application in the field of energy storage. Herein, Ag x NbO 2.5+ x /2 ceramics were successfully synthesized via solid state reaction with the x ranged from 1 to 0.92. The effect of silver deficiency on structure, dielectric properties and energy storage performance was investigated. As x value decreased from 1 to 0.94, the unit volume of Ag x NbO 2.5+ x /2 ceramics contracted. Meanwhile, all the compositions displayed double hysteresis loops with reduced P max , P r and enhanced transformation fields (E F and E B) as functions of silver deficiency. Silver deficiency stabilized the antiferroelectric state in the FIE (-like) phase and improved the energy storage performance of AgNbO 3 ceramics. Hence, an enhanced energy storage performance (W rec = 3.1 J/cm3, η = 49%) were achieved in Ag 0.94 NbO 2.97 ceramic. [ABSTRACT FROM AUTHOR]

This study investigated the effect of corn straw biochar on the decomposition, nutrient transformation, and bacterial community characteristics in the corn straw decomposition process. A 90-day microcosm incubation experiment was performed to assess the effects of corn straw biochar (500 °C, 1 h) on the corn straw decomposition process and the resulting product. Four biochar amendment rates (0%, 5, 10, and 15%, as mass fractions of biochar) and three different addition times (1st day, 30th day, and 60th day) were set in total. The results showed that corn straw biochar significantly increased the pH of the corn straw decomposition process by 0.71–0.73 and increased the electrical conductivity value by 0.64–1.07 μS/cm over that of the controls. In addition, biochar was shown to increase the temperature rise rate and temperature peak of the straw maturation system, and advance the process of straw maturation by 10 days. Thus, treatment with corn straw biochar could accelerate the corn straw decomposition process and change the conditions for microorganisms involved in the process. Furthermore, biochar additions significantly decreased the organic matter content by 9.67% under B3 and T1 treatment, and enhanced the N, P2O5, and K2O contents of the straw decomposition product by 0.36, 0.19, and 0.88% under B3 and T1 treatment. Biochar additions could increase the abundance of several effective bacteria closely related to the N, P2O5, and K2O contents of the straw maturation product. The growth of these bacteria was likely to be affected by the increase in pH with biochar addition, which enabled the improvement of the nutrient mineralization process. [ABSTRACT FROM AUTHOR]

Objective: TCP1 is one of the eight subunits of the TCP1 ring complex (TRiC) or the multi-protein mammalian cytosolic chaperone complex. TRiC participates in protein folding and regulates the expression of multiple signaling proteins and cytoskeletal components in cells. Although the clinical importance of its subunits has been clarified in various carcinomas, the function of TCP1 in ovarian cancer (OC) remains unclear. We aimed to identify the association between the expression of TCP1 and the development of epithelial OC (EOC) and patient prognosis, and explore the underlying mechanisms of TCP1 on the tumor progression of OC cells. Methods: TCP1 protein expression was tested in various ovarian tissues by immunohistochemistry, and the correlation between TCP1 expression and clinical physiologic or pathologic parameters of patients with EOC was analyzed. The relationship between TCP1 expression and the prognosis of patients with OC was investigated and analyzed using the Kaplan–Meier (KM) plotter online database. The expression level of TCP1 was then tested in different OC cell lines by Western blotting. Further, a model using OC cell line A2780 was constructed to study the functions of TCP1 in growth, migration, and invasion of human EOC cells. Finally, the possible regulating signaling pathways were discussed. Results: TCP1 protein expression in OC or borderline tissues was significantly higher than that in benign ovarian tumors and normal ovarian tissue. The upregulated expression of TCP1 in OC was positively associated with the differentiation grade and FIGO stage of tumors and predicted poor clinical outcomes. Compared with IOSE-80 cells, TCP1 protein was overexpressed in A2780 cells. TCP1 knockdown using shRNA lentivirus inhibited the viability of A2780 cells. Western blotting showed that the phosphatidylinositol-3 kinase (PI3K) signaling pathway was activated in the tumor invasion in EOC driven by TCP1. Conclusion: Upregulated TCP1 is correlated with the poor prognosis of patients with OC. The mechanism of cancer progression promoted by TCP1 upregulation may be linked to the activation of the PI3K signaling pathway, and TCP1 may serve as a novel target for the treatment of OC. [ABSTRACT FROM AUTHOR]

A spiral sound wave transducer comprised of longitudinal vibrating elements has been proposed. This transducer was made from eight uniform radial distributed longitudinal vibrating elements, which could effectively generate low frequency underwater acoustic spiral waves. We discuss the production theory of spiral sound waves, which could be synthesized by two orthogonal acoustic dipoles with a phase difference of 90 degrees. The excitation voltage distribution of the transducer for emitting a spiral sound wave and the measurement method for the transducer is given. Three-dimensional finite element modeling (FEM)of the transducer was established for simulating the vibration modes and the acoustic characteristics of the transducers. Further, we fabricated a spiral sound wave transducer based on our design and simulations. It was found that the resonance frequency of the transducer was 10.8 kHz and that the transmitting voltage resonance was 140.5 dB. The underwater sound field measurements demonstrate that our designed transducer based on the longitudinal elements could successfully generate spiral sound waves. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of radiofrequency ablation for low-risk papillary thyroid microcarcinoma (PTMC) in patients aged 55 years or older. This retrospective study included 95 patients aged 55 years or older who underwent radiofrequency ablation (RFA) for PTMCs between June 2014 and January 2019. Incidence and duration of postoperative complications were recorded and evaluated. Tumor volume and volume reduction rate (VRR) changes were calculated. Patients were also closely monitored for tumor recurrence, regrowth, and lymph node metastasis. All nodules were completely ablated. The mean initial volume of the ablated thyroid nodules was 107.27 ± 99.10 mm3, and the volume decreased significantly during the follow-up time. The VRR in 1st, 3rd, 6th, 12th, 18th, 24th and 36th month were −591.64 ± 623.65%, −170.89 ± 319.51%, 9.74 ± 128.43%, 77.99 ± 45.26%, 99.35 ± 3.61%, 99.45 ± 3.05% and 99.78 ± 1.54%, respectively. No patient had any life-threatening complications. One patient had lymph node metastasis and one had a recurrence; both underwent a second radiofrequency ablation treatment and achieved satisfactory treatment results. Our study suggests that radiofrequency ablation is a safe and effective option for low-risk PTMC in patients aged 55 years or older who are at a high risk of general anesthesia and postoperative complications or those who refuse surgery. [ABSTRACT FROM AUTHOR]

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients. [ABSTRACT FROM AUTHOR]

The evolution of jaws has played a major role in the success of vertebrate expansion into a wide variety of ecological niches. A fundamental, yet unresolved, question in craniofacial biology is about the origin of the premaxilla, the most distal bone present in the upper jaw of all amniotes. Recent reports have suggested that the mammalian premaxilla is derived from embryonic maxillary prominences rather than the frontonasal ectomesenchyme as previously shown in studies of chicken embryos. However, whether mammalian embryonic frontonasal ectomesenchyme contributes to the premaxillary bone has not been investigated and a tool to trace the contributions of the frontonasal ectomesenchyme to facial structures in mammals is lacking. The expression of the Alx3 gene is activated highly specifically in the frontonasal ectomesenchyme, but not in the maxillary mesenchyme, from the beginning of facial morphogenesis in mice. Here, we report the generation and characterization of a novel Alx3 CreERT2 knock-in mouse line that express tamoxifen-inducible Cre DNA recombinase from the Alx3 locus. Tamoxifen treatment of Alx3 CreERT2/+; Rosa26 mTmG/+ embryos at E7.5, E8.5, E9.5, and E10.5, each induced specific labeling of the embryonic medial nasal and lateral nasal mesenchyme but not the maxillary mesenchyme. Lineage tracing of Alx3 CreERT2 -labeled frontonasal mesenchyme from E9.5 to E16.5 clearly showed that the frontonasal mesenchyme cells give rise to the osteoblasts generating the premaxillary bone. Furthermore, we characterize a Dlx1-Cre BAC transgenic mouse line that expresses Cre activity in the embryonic maxillary but not the frontonasal mesenchyme and show that the Dlx1-Cre labeled embryonic maxillary mesenchyme cells contribute to the maxillary bone as well as the soft tissues lateral to both the premaxillary and maxillary bones but not to the premaxillary bone. These results clearly demonstrate the developmental origin of the premaxillary bone from embryonic frontonasal ectomesenchyme cells in mice and confirm the evolutionary homology of the premaxilla across amniotes. [Display omitted] • Embryonic origin of mammalian premaxilla is controversial and not well studied. • Alx3 CreERT2 mice enable specific genetic analysis of frontonasal development. • Lineage tracing shows frontonasal mesenchyme gives rise to mouse premaxillary bone. • Results reject recently proposed unique embryonic origin of mammalian premaxilla. • This paper clarifies embryonic origins and homology of mammalian facial bones. [ABSTRACT FROM AUTHOR]

Objective(s): Here we investigated the regulation of Th17 and Treg cells in orthodontic tooth movement during periodontal inflammation. Materials and Methods: Fifty-six SD rats were divided into a control (24 rats) and a tooth movement group during the recovery stage of periodontitis (RM group, 32 rats). Periodontitis was established by silk ligation and local injection of LPS. Orthodontic tooth movement was achieved by nickel-titanium springs on the maxillary first molars. The proportions of Th17 cells and Treg cells were evaluated by flow cytometry. Gene expression of ROR-t and Foxp3 was determined by real-time PCR. Expression of ROR-?t, Foxp3, RANK, RANKL, and OPG was detected by immunohistochemical staining. Osteoclasts were detected by TRAP staining. Relationships between Th17/Treg cells, osteoclasts, and related factors were estimated by correlation and regression analysis. Results: During orthodontic tooth movement in the recovery stage of periodontitis, the proportion of Th17 cells, ROR-t, RANK, osteoclasts, and the RANKL/OPG ratio increased and then decreased. The proportion of Treg cells and Foxp3 increased, then decreased, and increased again. Levels of RANKL and OPG increased, then decreased, then increased, and finally decreased. The Th17/Treg ratio initially decreased, then increased, and decreased again. Th17 cells were positively correlated with RANK and RANKL, the RANKL/OPG ratio, and counts of osteoclasts. Treg cells were negatively correlated with RANK expression and numbers of osteoclasts. The Th17/Treg ratio was positively correlated with RANK expression and numbers of osteoclasts. Conclusion: Under periodontal inflammation conditions, the Th17/Treg ratio might regulate orthodontic tooth movement through changing osteoclasts metabolism. [ABSTRACT FROM AUTHOR]

Pd‐catalyzed spiroannulation of bromophenylnaphthalenols with acetylenes to achieve asymmetric dearomatization is a powerful way to construct chiral spiro‐compounds. DFT calculations with the M06 functional have been performed to reveal the mechanism and enantioselectivity of this reaction. After reversible oxidative addition of aryl bromide to Pd(0), acetylene insertion into the Pd−C(aryl) bond is considered to be the rate‐ and enantioselectivity determining step. Subsequent deprotonation and reductive elimination then give the spiroannulation product. The overlay and noncovalent interaction analysis of the critical transition states were used to reveal the origin of the enantioselectivity for this reaction. We found that the axial chirality of the naphthol moiety affects the relative free energies of the corresponding transition states, whereas the enantioselectivity is controlled by the steric repulsion between the naphthol moiety and the ligand. [ABSTRACT FROM AUTHOR]

A theoretical study of the mechanism and regioselectivity of 1,3‐dipolar cycloaddition of nitrile oxides to 3‐methylene indolone has been performed by density functional theory at the M06‐2X/6‐311++G(d,p) level of theory. The results indicate that the concerted pathway is more favorable than the stepwise pathway. Investigation of the regioselectivity of this reaction shows that the main product is predicted to be 3,5‐substituted isoxazoline derivatives, which is consistent with experimental observations. The substituent effect of nitrile oxides on the reactivity and regioselectivity were also investigated. The opposite regioselectivity was observed for nitrile oxides with electron‐donating groups (methyl and phenyl) compared with electron‐withdrawing groups (CN and CO2Me). Distortion–interaction energy analysis shows that the reactivity of 1,3‐dipolar cycloaddition of nitrile oxides to 3‐methylene indolone is controlled by both the distortion and interaction energies. Natural population analysis indicates that the carbon atom of the 1,3‐dipole prefers to bond to the terminal carbon atom of the exocyclic double bond of 3‐methylene indolone, forming the 3,5‐substituted isoxazoline product. Frontier molecular orbital analysis shows that the regioselectivity is controlled by the orbital interaction between the lowest unoccupied molecular orbital of the nitrile oxide and the highest occupied molecular orbital of 3‐methylene indolone. [ABSTRACT FROM AUTHOR]

Decision making is a critical component of a new drug development process. Based on results from an early clinical trial such as a proof of concept trial, the sponsor can decide whether to continue, stop, or defer the development of the drug. To simplify and harmonize the decision‐making process, decision criteria have been proposed in the literature. One of them is to exam the location of a confidence bar relative to the target value and lower reference value of the treatment effect. In this research, we modify an existing approach by moving some of the "stop" decision to "consider" decision so that the chance of directly terminating the development of a potentially valuable drug can be reduced. As Bayesian analysis has certain flexibilities and can borrow historical information through an inferential prior, we apply the Bayesian analysis to the trial planning and decision making. Via a design prior, we can also calculate the probabilities of various decision outcomes in relationship with the sample size and the other parameters to help the study design. An example and a series of computations are used to illustrate the applications, assess the operating characteristics, and compare the performances of different approaches. [ABSTRACT FROM AUTHOR]