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The mechanism related to ovarian follicular is complex, which has not been fully elucidated. Abundant reports have confirmed that the ovarian function development is closely related to sympathetic innervation. As one of the major neurotransmitters, norepinephrine (NE) is considered an effective regulator of ovarian functions like granulosa cell (GC) apoptosis. However, the mechanism between NE and GC apoptosis in rat is still unclear. In our study, GCs were isolated and cultured in vitro with NE treatment. The apoptosis of GCs was facilitated by NE. Wilms tumor 1 (WT1) was found to be significantly downregulated in GCs after NE treatment, and overexpression of WT1 repressed apoptosis in rat GCs induced by NE. rno-miR-128-3p was found to be significantly enhanced by NE in GCs, and inhibition of rno-miR-128-3p repressed apoptosis in rat GCs induced by NE. Mechanistically, rno-miR-128-3p interacted with WT1 and repressed its expression. In summary, inhibition of rno-miR-128-3p may enhance WT1 expression, and then repress NE-induced apoptosis in rat GCs. Our research may provide a new insight for the improvement of ovarian follicular development.

Large separation of magnetic levels and slow relaxation in metal complexes are desirable properties of single-molecule magnets (SMMs). Spin-phonon coupling (interactions of magnetic levels with phonons) is ubiquitous, leading to magnetic relaxation and loss of memory in SMMs and quantum coherence in qubits. Direct observation of magnetic transitions and spin-phonon coupling in molecules is challenging. We have found that far-IR magnetic spectra (FIRMS) of Co(PPh3)2X2 (Co-X; X = Cl, Br, I) reveal rarely observed spin-phonon coupling as avoided crossings between magnetic and u-symmetry phonon transitions. Inelastic neutron scattering (INS) gives phonon spectra. Calculations using VASP and Phonopy programs gave phonon symmetries and movies. Magnetic transitions among zero-field split (ZFS) levels of the S = 3/2 electronic ground state were probed by INS, high-frequency and -field EPR (HFEPR), FIRMS, and frequency-domain FT terahertz EPR (FD-FT THz-EPR), giving magnetic excitation spectra and determining ZFS parameters (D, E) and g values. Ligand-field theory (LFT) was used to analyze earlier electronic absorption spectra and give calculated ZFS parameters matching those from the experiments. DFT calculations also gave spin densities in Co-X, showing that the larger Co(II) spin density in a molecule is, the larger its ZFS magnitude is. The current work reveals dynamics of magnetic and phonons excitations in SMMs. Studies of such couplings in the future would help understand how spin-phonon coupling may lead to magnetic relaxation and develop guidance to control such coupling.

Trichoderma is an important and widely used plant growth-promoting fungus (PGPF). In this study, stevia residue amended with amino acids hydrolyzed from animal carcasses was used for the production of Trichoderma guizhouense NJAU 4742 by solid-state fermentation, and then its potential to promote corn plant growth was evaluated in combination with chemical fertilizer (CF) or organic fertilizer (OF). The highest spore number of 7×109 CFU g−1 fresh weight was obtained under the following optimal parameters: material ratio of 50% (stevia residue:rice bran=1:1), pH value of 3.0 (amended with 6.67% amino acids), initial moisture content of 60%, inoculum size of 10%, material thickness of 3 cm and an incubation time of 4 days. The aboveground corn plant biomass obtained with T. guizhouense applied alone and with CF treatments were slightly higher than those of no fertilizer control and CF treatments, respectively. However, T. guizhouense applied with OF significantly (P

Three mononuclear tetrakis(pseudohalido)-cobalt(II) complexes (Ph4P)2[Co(E)4] (E = N3−, 1; NCO−, 2; NCS−, 3) have been synthesized and structurally characterized. Each compound contains a distorted tetrahedral Co2+ ion coordinated by four pseudohalide ligands. The magnetic properties of 1–3 have been studied using direct-current magnetic measurements and high-frequency and -field EPR spectroscopy (HFEPR), suggesting easy-axis magnetic anisotropy for 1 and 2 and easy-plane anisotropy for 3. Analysis of the HFEPR spectra yielded D values of −5.23 and +3.63 cm−1 for 2 and 3, respectively. The absence of the EPR signal in 1 is consistent with a large, negative value of the zero-field splitting (ZFS) parameter D in 1. The nature of magnetic anisotropies of 1–3 has also been confirmed by ab initio calculations. The calculated D values are consistent with those determined using magnetometry and HFEPR studies. Alternating current (AC) magnetic susceptibilities reveal slow magnetic relaxation under an applied magnetic field, thus indicating that 1–3 are field-induced single-ion magnets (SIMs).

The diglyceryl phthalate epoxy resin contains a benzene ring in its molecular structure, and its molecular weight is small. In addition to the generality of epoxy resins, it also has the advantages of low viscosity, moderate reactivity, high adhesion, good compatibility, excellent electrical insulation and ultra-low temperature, and good weather resistance. It has good adhesion with carbon fiber, and it is suitable to make carbon fiber composite material. Based on this background, this article mainly focuses on the seat art design, and uses the wrapping method to analyze the preparation of the carbon fiber composite resin matrix. The optimal reaction conditions are determined by changing the reaction during the preparation of the thermoplastic resin matrix. / PA = 1.9, esterification time 120min, cyclization time 70min, reaction temperature 110 °C, amount of promoter water 6g, concentration of cyclizing agent sodium hydroxide solution 30%. The resin synthesized in this case is a light-yellow transparent liquid with an epoxy value of 0.51 (mol / 100g).

Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1–10 μM) concentration-dependently prevented H(2)O(2)-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Pretreatment with JE-133 significantly alleviated H(2)O(2)-induced apoptotic changes. These protective effects could not be simply attributed to the direct free radical scavenging as JE-133 had moderate activity in reducing DPPH free radical. Further study revealed that pretreatment with JE-133 (10 μM) significantly decreased the phosphorylation of MAPK pathway proteins, especially ERK and P38, in the neuronal cells. In addition, blocking PI3K/Akt pathway using LY294002 partially counteracted the cell viability-enhancing effect of JE-133. We conclude that JE-133 exerts neuroprotection associated with dual regulative mechanisms and consequently activating cell survival and inhibiting apoptotic changes, which may provide important clues for the development of effective neuroprotective drug lead/candidate.

Spin–Phonon coupling plays a critical role in magnetic relaxation in single-molecule magnets (SMMs) and molecular qubits. Yet, few studies of its nature have been conducted. Phonons here refer to both intermolecular and intramolecular vibrations. In the current work, we show Spin–Phonon couplings between IR-active phonons in a lanthanide molecular complex and Kramers doublets (from the crystal field). For the SMM Er[N(SiMe(3))(2)](3) (1, Me = methyl), the couplings are observed in the far-IR magnetospectroscopy (FIRMS) of crystals with coupling constants ≈ 2−3 cm(−1). In particular, one of the magnetic excitations couples to at least two phonon excitations. The FIRMS reveals at least three magnetic excitations (within the (4)I(15/2) ground state/manifold; hereafter, manifold) at 0 T at 104, ∼180, and 245 cm(−1), corresponding to transitions from the ground state, M(J) = ±15/2, to the first three excited states, M(J) = ±13/2, ±11/2, and ±9/2, respectively. The transition between the ground and first excited Kramers doublet in 1 is also observed in inelastic neutron scattering (INS) spectroscopy, moving to a higher energy with an increasing magnetic field. INS also gives complete phonon spectra of 1. Periodic DFT computations provide the energies of all phonon excitations, which compare well with the spectra from INS, supporting the assignment of the inter-Kramers doublet (magnetic) transitions in the spectra. The current studies unveil and measure the Spin–Phonon couplings in a typical lanthanide complex and throw light on the origin of the Spin–Phonon entanglement.

Two mononuclear tetrahedral Co(II) complexes (HNEt3)2[Co(L1)2]·H2O (1) and (Bu4N)2[Co(L2)2]·H2O (2) (H2L1 = N,N′-bis(p-toluenesulfony1)oxamide, H2L2 = N,N′-diphenyloxamide) have been synthesized, a...

Mutations in mitochondrial DNA (mtDNA) have been associated with deafness and their pathophysiology remains poorly understood. In this study, we investigated the pathogenic mechanism of deafness-associated 7505A > G variant in the mitochondrial tRNASer(UCN). The m.7505A > G variant affected the highly conserved adenine at position 11 (A11), disrupted the highly conserved A11-U24 base-pairing of DHU stem of tRNASer(UCN) and introduced a tertiary base pairing (G11-C56) with the C56 in the TΨC loop. We therefore hypothesized that the m.7505A > G variant altered both structure and function of tRNASer(UCN). We demonstrated that the m.7505A > G variant perturbed the conformation and stability of tRNASer(UCN), as indicated by an increased melting temperature and electrophoretic mobility of the mutated tRNA compared with the wild type molecule. Using the cybrids constructed by transferring mitochondria from the Chinese family into mitochondrial DNA (mtDNA)-less cells, we demonstrated the m.7505A > G variant led to significantly decreased steady-state levels of tRNASer(UCN) in the mutant cybrids, as compared with those of control cybrids. The aberrant tRNASer(UCN) metabolism resulted in the variable decreases in mtDNA-encoded polypeptides in the mutant cybrids. Furthermore, we demonstrated that the m.7505A > G variant decreased the activities of mitochondrial respiratory complexes I, III and IV, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in the mutant cybrids. These results demonstrated that the m.7505A > G variant affected both structure and function of tRNASer(UCN) and consequently altered mitochondrial function. Our findings highlighted critical insights into the pathophysiology of maternally inherited deafness, which is manifested by the aberrant tRNA metabolism.

Tb3+-doped carbon dots (Tb3+@CDs) were prepared in a facile hydrothermal method by using ammonium citrate as carbon source and Tb3+ as dopant. A 15-bp GT-rich single-strand DNA (ssDNA) was introduced to sensitize Tb3+ via the antenna effect for generating two fluorescence signals (CDs and Tb3+), forming a conjugate of Tb3+@CDs/ssDNA. The ratiometric fluorescence of Tb3+@CDs/ssDNA could be reversibly regulated by Ag+ and Cys, in which the fluorescence peak at 546 nm of Tb3+ could be switched to “On” or “Off” as the signal indicator while the fluorescence peak at 444 nm of CDs remained constant as the build-in reference. The proposed Ag+/Cys-mediated reversible fluorescence changes in Tb3+@CDs/ssDNA was also proven for the design of a self-calibrating ratiometric fluorescence logic system. By integrated with the specific reaction between H2O2 and Cys, Tb3+@CDs/ssDNA was applied for ratiometric fluorescence detection of H2O2. More importantly, the sensing strategy could be further successfully extended to the monitoring of H2O2-produced oxidase-related reactions, such as GOx-biocatalyzed oxidation of glucose (the limit of detection: 0.06 μM) and was well applied in rat serum compared to commercial kits. This work unveiled a novel ratiometric fluorescent design, which is cost-effective, simple to prepare and easy-to-use without chemical modification or fluorescence labeling.

Heat stroke can induce a systemic inflammatory response, which may lead to multi‑organ dysfunction including acute kidney injury (AKI) and electrolyte disturbances. To investigate the pathogenesis of heat stroke (HS)‑related AKI, a mouse model of HS was induced by increasing the animal's core temperature to 41˚C. Blood samples obtained from the tail vein were used to measure plasma glucose and creatinine levels. Micro‑positron emission tomography‑computed tomography (micro‑PET/CT), Hamp;E staining and transmission electron microscopy were conducted to examine metabolic and morphological changes in the mouse kidneys. Immunohistochemistry (IHC) and western blot analyses were performed to investigate the expression of apoptosis‑inducing factor mitochondria‑associated 2 (Aifm2), high‑mobility group box 1 (HMGB1) and receptor for advanced glycosylation end products (RAGE). Liquid chromatography‑mass spectrometry analysis was conducted to find differential metabolites and signaling pathways. The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas micro‑PET/CT revealed active metabolism in the whole body of HS mice. Hamp;E and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. Finally, 136 differential metabolites were screened out, and enrichment of the 'biosynthesis of unsaturated fatty acids' pathway was detected. HS‑associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway. Metabolomics indicated increased adrenic acid, docosahexaenoic acid and eicosapentaenoic acid may serve as metabolic biomarkers for AKI in HS. The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS‑related AKI.

Introduction. In our previous study, it has been confirmed that formaldehyde (FA) not only inhibits the proliferative activity, but also causes DNA-protein crosslinks (DPCs) formation in bone marrow mesenchymal stem cells (BMSCs). The purpose of this study was to detect the protective effect of astragalus polysaccharide (APS) against the cytotoxicity and genotoxicity of BMSCs exposed to FA, and to explore potential molecular mechanisms of APS activity. Material and methods. Human BMSCs were cultured in vitro and randomly divided into control cells (Ctrl group), FA-treated cells (FA group, 120 μmol/L), and cells incubated with FA and increasing concentrations (40, 100, or 400 μg/mL) of APS (FA + APS groups). Cytotoxicity was measured by MTT assay. DNA strand breakage, DNA-protein crosslinks (DPCs), and micronucleus formation were respectively detected by comet assay, KCl-SDS precipitation assay, and micronucleus assay. The mRNA and protein expression level of xeroderma pigmentosum group A (XPA), xeroderma pigmentosum group C (XPC), excision repair cross-complementation group 1 (ERCC1), replication protein A1 (RPA1), and replication protein A2 (RPA2) were all detected by qRT-PCR and Western Blot. Results. Compared with the FA group, the cytotoxicity, DNA strand breakage, DPCs, and micronucleus levels were decreased significantly in FA + APS groups (P < 0.01). Meanwhile, the mRNA and protein expression of XPA, XPC, ERCC1, RPA1, and RPA2 were up regulated significantly in the FA + APS groups (P < 0.05) with the most prominent effect of the 100 μg/mL APS. Conclusions. Our results suggest that APS can protect the cytotoxicity and genotoxicity of human BMSCs induced by FA. The mechanism may be associated with up-regulated expression of XPA, XPC, ERCC1, RPA1, and RPA2 in the nucleotide excision repair (NER) pathway which promotes DNA damage repair.

Background This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC). Methods The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 - ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2 - ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day) + EXE (25 mg/day) orally. Results A total of 235 patients received >= 1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (>= 20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained. Conclusion The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE + EXE could be a viable treatment option for the postmenopausal women with HR+, HER2 - ABC in Asian region., Novartis Pharma AG, Base, Switzerland; NovartisNovartis, The EVEREXES trial was funded by Novartis Pharma AG, Base, Switzerland. Funding for medical editorial support was also provided by Novartis.

DNA-encoded small molecule libraries (DELs) have enabled discovery of novel inhibitors for many distinct protein targets of therapeutic value through screening of libraries with up to billions of unique small molecules. We demonstrate a new approach applying machine learning to DEL selection data by identifying active molecules from a large commercial collection and a virtual library of easily synthesizable compounds. We train models using only DEL selection data and apply automated or automatable filters with chemist review restricted to the removal of molecules with potential for instability or reactivity. We validate this approach with a large prospective study (nearly 2000 compounds tested) across three diverse protein targets: sEH (a hydrolase), ER{\alpha} (a nuclear receptor), and c-KIT (a kinase). The approach is effective, with an overall hit rate of {\sim}30% at 30 {\textmu}M and discovery of potent compounds (IC50

BACKGROUND The present study explored the expression of coiled-coil domain-containing 34 (CCDC34) in cervical cancer (CC) and its prognostic value. MATERIAL AND METHODS GEPIA and Oncomine cancer databases were mined to predict the CCDC34 differential expression level between a CC group and a normal group. Immunohistochemistry was performed to examine the CCDC34 expression in 67 CC and corresponding adjacent tissues. CD31 and vascular endothelial growth factor (VEGF) were stained to reflect tumor angiogenesis in 67 CC tissues. Kaplan-Meier univariate and Cox multivariate survival analysis were done to evaluate the correlation between CCDC34 expression and prognosis of CC patients. RESULTS Both GEPIA and Oncomine cancer databases mining results revealed that CCDC34 was more highly expressed in the CC group than in the normal group (all P

Four dinuclear Ir I complexes with macrocyclic diamine‐tetracarbene ligands were synthesized and characterized, two of which and a related mononuclear complex were found to be the first examples of Ir N‐heterocyclic carbene complexes exhibiting catalytic performance toward 1,4‐addition of arylboronic acids to cyclohex‐1‐en‐2‐one.

Four macrocyclic hybrid salts with different numbers of benzimidazolium and amine units, [H2L][PF6]2 (L = L1, L2, L3) and [H4L4][PF6]4, have been employed as the heterocyclic carbene (NHC) precursors toward new Ag(I)– and Au(I)–NHC complexes. Three trinuclear and one tetranuclear Ag(I) complexes 1–4 have been obtained from the reactions of the NHC precursors and Ag2O in acetonitrile. Four dinuclear Au(I)–NHC complexes 5–8 have been prepared by reacting the NHC precursors and AuCl(SMe2) in the presence of NaOAc in DMF. The molecular structures of all the complexes are established by single-crystal X-ray diffraction studies. The metal ions in the Ag(I) complexes 1–3 and the Au(I) complexes 5–7 are coordinated with two macrocyclic NHC ligands to form a sandwiched structure. In contrast, a trinuclear Ag3 core is located in the cavity of one macrocyclic ligand in [Ag3(L4)][PF6]3 (4). The photoluminescence properties of Au(I) complexes 5–8 have also been investigated.

Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A→G mutation in mitochondrial tRNAMet. The m.4435A→G mutation affected a highly conserved adenosine at position 37, 3′ adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m.4435A→G mutation introduced an m1G37 modification of tRNAMet, altering its structure and function. Primer extension and methylation activity assays indeed confirmed that the m.4435A→G mutation created a tRNA methyltransferase 5 (TRMT5)–catalyzed m1G37 modification of tRNAMet. We found that this mutation altered the tRNAMet structure, indicated by an increased melting temperature and electrophoretic mobility of the mutated tRNA compared with the wildtype molecule. We demonstrated that cybrid cell lines carrying the m.4435A→G mutation exhibited significantly decreased efficiency in aminoacylation and steady-state levels of tRNAMet, as compared with those of control cybrids. The aberrant tRNAMet metabolism resulted in variable decreases in mitochondrial DNA (mtDNA)-encoded polypeptides in the mutant cybrids. Furthermore, we found that the m.4435A→G mutation caused respiratory deficiency, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in mutant cybrids. These results demonstrated that an aberrant m1G37 modification of mitochondrial tRNAMet affected the structure and function of its tRNA and consequently altered mitochondrial function. Our findings provide critical insights into the pathophysiology of maternally inherited hypertension, which is manifested by the deficient tRNA nucleotide modification.

A series of Ni(II), Pd(II) and Pt(II) complexes [ML][PF6]2 [L = L1, M = Ni (1), Pd (2), Pt (3); L = L2, M = Ni (4), Pd (5), Pt (6)] and [Pt(L2)(acac)] (7) have been prepared by the reactions of two tetradentate macrocyclic amine-NHC ligand precursors, [H2L1][PF6]2 and [H2L2][PF6]2, with Ni(OAc)2·4H2O, Pd(OAc)2 and Pt(acac)2 in the presence of NaOAc. Complex 7 is isolated along with 6 from the same reaction between [H2L2][PF6]2 and Pt(acac)2. There are two atropisomers in 1–3 and two achiral conformers in 4–6. The crystal structures of 1–3 and one conformer of 4–6 (4a–6a) have been determined by single-crystal X-ray diffraction studies. The metal ion is found to reside in the cavity of the macrocyclic ring and adopts a square-planar configuration. Detailed NMR studies including variable-temperature NMR spectroscopy reveal a dynamic interconverting process between two atropisomers of 1–3 in the solutions via a ring twisting mechanism. Two conformers in the equilibrated solution of 4–6, probably arising from the orientation of two amine N–H bonds with respect to the coordination plane, exchange slowly. Time-dependent 1H NMR spectra show that one conformer (4a–6a) in solution converts into the other (4b–6b) via the inversion of the nitrogen atom.

Tri-amidinate chloride complexes M[MeC(NiPr)2]3Cl [M = Zr (1), Hf (2)] have been prepared from MCl4 and lithium amidinate Li[MeC(NiPr)2]. The uncommon hepta-coordinated complexes Zr-Cl (1) and Hf-Cl (2) undergo metathesis reactions with 1 equiv. of MeLi and EtMgCl to give alkyl derivatives M[MeC(NiPr)2]3R [R = Me, M = Zr (3), Hf (4); R = Et, M = Zr (5), Hf (6)]. The dynamic behaviors of Zr-Cl (1) and Hf-Cl (2) in solution have been studied using variable-temperature 1H NMR (VT 1H NMR), giving activation parameters ΔH‡, ΔS‡, and ΔG‡ for several exchange processes in Zr-Cl (1) and Hf-Cl (2). 1H-15N gHMBC NMR spectroscopy gives the chemical shifts of the N atoms in 1-6. The 1H-15N gHMBC NMR spectra of 1-4 at elevated temperatures are needed to obtain signals. Crystal structures of Zr-Cl (1), Hf-Cl (2), Zr-Et (5), and Hf-Et (6) have been determined via X-ray diffraction. DART-MS studies of Zr-Cl (1) and Hf-Cl (2) in air give MS of 1-2, cations M[MeC(NiPr)2]3+ [M = Zr (7), Hf (8)], and hydroxyl complexes M[MeC(NiPr)2]3OH [M = Zr (9), Hf (10)]. In comparison, DART-MS spectra of 3-6 in air show only 7-8 and 9-10, indicating lability of the alkyl ligands and/or their fast hydrolysis by moisture.

Due to the abundant presence of Na, sodium ion batteries show great potential in electric vehicles, portable electronic devices, and energy storage systems. Recently, layered oxides with P2 structure have considered as the promising cathodes for sodium ion batteries. In this paper, P2-type layered oxide Na0.67Ni0.33Mn0.67O2 was prepared by a simple solid-state method and enhanced by Cu/Mo co-substitution. The Cu/Mo co-doped sample Na0.67Ni0.33Mn0.57Cu0.05Mo0.05O2 exhibited improved electrochemical performance compared to the raw material. It delivered an initial reversible discharge capacity of 142 mAh g−1 in the voltage range from 2 to 4.5 V at 0.2 C with a high capacity retention of 91.5%. This work may provide a promising strategy to develop electrochemical performance of cathode materials for advanced sodium ion batteries.

Cashmere is an important economic resource for the agricultural industry. The secondary hair follicle cycle can control the yield and quality of cashmere. Therefore, to improve the yield and quality of cashmere in Liaoning cashmere goats, an understanding of the skin proteomic changes in the secondary hair follicle cycle is needed. In this study, we used a label-free proteomics approach to analyze the protein expression profile of the secondary hair follicle cycle at three stages (telogen, anagen, and catagen) in goat neck skin. Proteomics, bioinformatics, and immunofluorescence assays were employed. We identified 57 differentially abundant proteins (DAPs) and discovered that the proteins of the keratin family were highly expressed in the anagen and catagen phases. The analyses indicated that nine keratin proteins (KRT25, KRT27, KRT19, KRT10, KRT77, KRT1, KRT24, KRT14, and KRT4) can be regarded as markers of the hair follicle cycle. KRT1 was located in both the inner and outer root sheath, whereas KRT14 was located in the inner root sheath and KRT19 only in the outer sheath. Phylogenetic analysis showed that these nine keratin proteins have common evolutionary precursors, and each category has similar expression patterns. Functional enrichment analysis indicated that the estrogen and ECM-receptor interaction signaling pathways play important roles in secondary hair follicle phases/cycles. These findings provide an important resource for protein information related to cashmere goats, and the identified DAPs can be further applied to improve cashmere quality and production.

NMR chemical shifts of d0 transition metal compounds show the following trends: (1) For single-bonded ligands such as M-H, M-CR3, M←NR3, M-SiR3 and M←PR3, 1H, 13C, 15N, 29Si and 31P shifts of these α atoms in the complexes of both first- and third-row transition metals are typically downfield from (or at higher frequencies than) those of second-row analogs with a “V-shape” (Trend 1). (2) For multiple-bonded ligands including those with d-p π bonds, such as M=CHR, M≡CR, M=NR, M=O and M F, 13C, 15N, 17O and 19F shifts of the α atoms in the complexes of first-, second- and third-row transition metals move consecutively upfield (or to lower frequencies) (Trend 2). NMR shifts of lanthanum(III) complexes help interpret Trend 1 in Group 3 congeners. Scandide (d-block) and lanthanide (f-block) contractions and relativistic effects are believed to contribute to the NMR shifts, leading to the observed trends. Comparisons are made with NMR chemical shifts of dn complexes and organic compounds. Since many chemical properties of the second- and third-row congeners such as Zr and Hf are similar, as a result of lanthanide contraction, the NMR chemical shifts are a rare property to distinguish compounds of the otherwise nearly identical congeners. The current paper points out the trends with our narrative interpretations of the trends.

Multidrug resistance is a major unresolved obstacle to successful cancer chemotherapy. It is often associated with an elevated efflux of a variety of anticancer drugs by ATP-binding cassette transporters including P-glycoprotein, BCRP and MRP1. In this study, the reversal effect of Ethyl lucidenates A on K562/A02 cells was investigated. At concentrations of 10 μM, Ethyl lucidenates A could reverse the resistance of K562/A02 to vincristine up to 7.59 folds. Mechanistically, Ethyl lucidenates A could increase the intracellular accumulation of vincristine in K562/A02 cells through inhibiting the P-glycoprotein mediated drug-transport activity by rhodamine accumulation assay and cell cycle analysis. Further mechanistic investigation found that Ethyl lucidenates A did not alter P-glycoprotein expression. In conclusion, Ethyl lucidenates A could reverse the multidrug resistance of K562/A02 cells via its influence on P-glycoprotein drug-transport activity and thus, be a potential multidrug resistance reversal agent.

A hexadentate macrocyclic N-heterocyclic carbene (NHC) ligand precursor (H4L)(PF6)4 containing four benzimidazolium and two secondary amine groups, has been synthesized and characterized. Coordination chemistry of this new macrocyclic diamine-tetracarbene ligand has been studied by the synthesis of its Ag(I), Au(I), Ni(II), and Pd(II) complexes. Reactions of (H4L)(PF6)4 with different equiv of Ag2O result in Ag(I) complexes [Ag(H2L)](PF6)3 (1) and [Ag2(H2L)](PF6)4 (2). A mononuclear Au(I) complex [Au(H2L)](PF6)3 (3) and a trinuclear Au(I) complex [Au3(H2L)(Cl)2](PF6) (4) are obtained by transmetalation of 1 and 2 with AuCl(SMe2), respectively. Reactions of (H4L)(PF6)4 with Ni(OAc)2 and Pd(OAc)2 in the presence of NaOAc yield [Ni(L)](PF6)2 (5) and [Pd(L)](PF6)2 (6), respectively, containing one Ni(II) and Pd(II) ion with distorted square-planar geometry. Using more NaOAc results in the formation of unusual dinuclear complexes [Ni2(L–2H)](PF6)2 (7) and [Pd2(L–2H)](PF6)2 (8) (L–2H = deprotonated ligand after...

The reactions of early-transition-metal complexes with H2O have been investigated. An understanding of these elementary steps promotes the design of precursors for the preparation of metal oxide materials or supported heterogeneous catalysts. Density functional theory (DFT) calculations have been conducted to investigate two elementary steps of the reactions between tungsten alkylidyne complexes and H2O, i.e., the addition of H2O to the W≡C bond and ligand hydrolysis. Four tungsten alkylidyne complexes, W(≡CSiMe3)(CH2SiMe3)3 (A-1), W(≡CSiMe3)(CH2tBu)3 (B-1), W(≡CtBu)(CH2tBu)3 (C-1), and W(≡CtBu)(OtBu)3 (D-1), have been compared. The DFT studies provide an energy profile of the two competing pathways. An additional H2O molecule can serve as a proton shuttle, accelerating the H2O addition reaction. The effect of atoms at the α and β positions has also been examined. Because the lone-pair electrons of an O atom at the α position can interact with the orbital of the proton, the barrier of the ligand-hydrolysi...

The present study aimed to investigate the roles of the µ-opioid receptor (MOR) and its related signaling pathways in the pathogenesis of premenstrual syndrome (PMS) liver-qi stagnation, along with the therapeutic effects of the Shu-Yu capsule in treating the condition. A PMS liver-qi stagnation rat model was established using a chronic restraint stress method. The protein expression level of MOR within rat hippocampal tissue was detected via western blot analysis and cyclic adenosine monophosphate (cAMP) levels within the supernatant of a rat hippocampal cell culture were determined by ELISA. The western blot analysis indicated that the hippocampal expression level of MOR was significantly elevated in the PMS liver-qi stagnation model group. However, subsequent treatment with a Shu-Yu capsule was found to significantly decrease the level of MOR expression. In addition, in vitro experiments were performed, whereby primary hippocampal neurons were treated with model rat serum. It was observed that the level of MOR expression was significantly elevated, while brain-derived neurotrophic factor (BDNF) and cAMP levels in the culture supernatant were significantly decreased. These effects were reversed by treatment with serum from the Shu-Yu capsule-treated rats. Furthermore, when treated with the MOR activator DAMGO, the following were significantly decreased in the primary neurons: Phosphorylation levels of cAMP response element binding protein and extracellular signal-regulated protein kinases (ERK); BDNF expression; and cAMP content in the culture supernatant. These effects were reversed in primary neurons treated with DAMGO and Shu-Yu-containing rat serum. Collectively, the data suggest that increased MOR expression and activation of the cAMP/ERK signaling pathway in the hippocampus may be involved in the pathogenesis of PMS liver-qi stagnation. Furthermore, the efficacy of the Shu-Yu capsule in treating the condition may be via its regulation of MOR receptor signaling.

Fourteen Ag(I), Au(I), Ni(II), Pd(II), and Pt(II) complexes with macrocyclic tetradentate N-heterocyclic carbene (NHC) ligands were prepared via reactions between three macrocyclic tetrabenzimidazolium salts and metal precursors. All except two Au complexes were characterized using single-crystal X-ray diffraction. Three different structures, including a trinuclear one containing a NHC–Ag–(H2O) moiety and a hexanuclear propeller-like supramolecular assembly, are found for Ag–NHC complexes. Nine complexes of group 10 metal ions adopt square-planar geometry, in which the different ring-sizes of the macrocyclic tetracarbene ligands lead to a variation of metal–carbene bond lengths. π–π stackings are observed between the rigid aromatic benzimidazole rings in the nickel group complexes.

An efficient preparation process for a novel Enterovirus 71 (EV71) vaccine was developed in this paper, which is a fused antigen by connecting the truncated capsid proteins of VP1, VP2 and VP3 into one molecule through flexible peptide linkers and expressed in E. coli as inclusion bodies. The fused protein was purified at denatured state through two-step ion exchange chromatography, with final purity above 95%, host cell proteins below 0.003% and residual DNA less than 50 ng/mL. During the following refolding and assembling process through dilution, the fused antigen precipitated completely, while the precipitation was efficiently inhibited with 2 M urea or 0.5 M arginine as an additive. Size exclusion chromatography analysis indicated the protein formed soluble aggregates with linear or rod-like appearance in transmission electron microscopy. These aggregates transformed into pentamers with a size of 15 nm at pH 8.0 after the additive removing. Moreover, most of the pentamers assembled as sphere-like particulates about 25–40 nm after being induced by calcium chloride. High antigen-specific IgG titer was elicited by immunization with the nanoparticles in mouse model. Splenocytes proliferative responses and cytokines analysis indicated this particulate antigen could induce humoral and cellular immune responses. These results lay foundations for developing the fused antigen as an alternative vaccine against hand-foot-and-mouth disease (HFMD) and for the large-scale production for E.coli-based vaccines.

We present the first examples of the coexistence of field induced slow magnetic relaxation and spin-crossover observed in five-coordinate cobalt(II) complexes [Co(12-TMC)(CH3CN)](X)2 (12-TMC = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane, X = BF4−, 1; PF6−, 2). The direct-current (dc) magnetic data show a gradual and incomplete spin-crossover at high temperature. 1 and 2 display frequency- and temperature-dependent alternating-current (ac) magnetic susceptibility under an applied dc field of 2500 Oe, which originates from the S = 1/2 spin state of Co(II) ions.

Mutagenized populations have provided important materials for introducing variation and identifying gene function in plants. In this study, an ethyl methanesulfonate (EMS)-induced soybean (Glycine max) population, consisting of 21,600 independent M2 lines, was developed. Over 1,000 M4 (5) families, with diverse abnormal phenotypes for seed composition, seed shape, plant morphology and maturity that are stably expressed across different environments and generations were identified. Phenotypic analysis of the population led to the identification of a yellow pigmentation mutant, gyl, that displayed significantly decreased chlorophyll (Chl) content and abnormal chloroplast development. Sequence analysis showed that gyl is allelic to MinnGold, where a different single nucleotide polymorphism variation in the Mg-chelatase subunit gene (ChlI1a) results in golden yellow leaves. A cleaved amplified polymorphic sequence marker was developed and may be applied to marker-assisted selection for the golden yellow phenotype in soybean breeding. We show that the newly developed soybean EMS mutant population has potential for functional genomics research and genetic improvement in soybean.

A protein/lanthanide complex (BSA/Tb3+)-based sensor array in two different pH buffers has been designed for high-throughput recognition and time-resolved fluorescence (TRF) detection of metal ions in biofluids. BSA, which acted as an antenna ligand, can sensitize the fluorescence of Tb3+ (i.e., antenna effect), while the presence of metal ions would lead to the corresponding conformational change of BSA for altering the antenna effect accompanied by a substantial TRF performance of Tb3+. This principle has also been fully proved by both experimental characterizations and coarse-grained molecular dynamics (CG-MD) studies. By using Tris-HCl buffer with different pHs (at 7.4 and 8.5), 17 metal ions have been well-distinguished by using our proposed BSA/Tb3+ sensor array. Moreover, the sensor array has the potential to discriminate different concentrations of the same metal ions and a mixture of metal ions. Remarkably, the detection of metal ions in biofluids can be realized by utilizing the presented sensor array, verifying its practical applications. The platform avoids the synthesis of multiplex sensing receptors, providing a new method for the construction of convenient and feasible lanthanide complex-based TRF sensing arrays.

Non-segmented negative-strand RNA viruses, such as measles, ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids, which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered, was determined at 4.8 Å resolution by cryo-electron microscopy. The clam-shaped structure is composed of two single-turn spirals packed in a back-to-back mode. This tightly packed structure functions as a seed for the assembly of a nucleocapsid from both directions, facilitating the growth of double-headed filaments with two separate RNA strings inside. Disruption of this structure by mutations in its loop interface yielded a single-headed unfunctional filament.

Three mononuclear six-coordinate Co(ii)-pseudohalide complexes [Co(L)X2] with two N-donor pseudohalido coligands occupying the cis-positions (X = NCS- (1), NCSe- (2) or N(CN)2- (3)), and a five-coordinate complex [Co(L)(NCO)][B(C6H5)4] (4) [L = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane (12-TMC)] have been prepared and structurally characterized. Easy-plane magnetic anisotropy for 1-3 and easy-axis anisotropy for 4 were revealed via the analyses of the direct-current magnetic data, high-frequency and -field EPR (HFEPR) spectra and ab initio theoretical calculations. They display slow magnetic relaxations under an external applied dc field. Typically, two slow relaxation processes were found in 1 and 2 while only one relaxation process occurs in 3 and 4. The Raman-like mechanism is found to be dominant in the studied temperature range in 1. For 2-4, the Raman process is dominant in the low temperature region, while the Orbach mechanism dominates in the high temperature range.

Insufficient blood supply is associated with high levels of necrosis in reconstructive surgery. Restoring blood flow to undersupplied ischemic tissue is the most important impact factor determining skin flap viability. Dietary nitrate, a significant source of nitric oxide, has multiple physiological functions, including regulator of blood flow, angiogenesis, and vasodilatation. However, the effects of dietary nitrate on ischemic skin flap remain unknown. The present study evaluated whether dietary nitrate supplementation altered blood flow of ischemic skin flap in rats. Our results showed that nitrate treatment significantly enhanced ischemic tissue survival. Mechanistically, nitrate therapy significantly increased serum nitrate and nitrite levels, blood perfusion, and angiogenesis. In addition, the circulating levels of Inflammatory mediators were decreased by nitrate supplementation. In conclusion, we demonstrated that dietary nitrate supplementation protected ischemic skin flap by enhancing ischemia-induced revascularization.

The transition metal oxide, such as iron oxide and Fe2O3/Al2O3 is cheap and industrialized that are widely used to catalyze the reaction of chlorine and oxygen with hydrogen in mixture gas to remove hydrogen from tail chlorine at low temperature. The reaction gas was prepared by the same composition with industrial tail chlorine, namely Cl2 (65% ~ 80%), O2 (8% ~ 10%), N2 (6% ~16%) and H2 (1.5% ~ 4%). In this experiment, the fixed bed reactor and iron oxide or Fe2O3/Al2O3 were used as the reaction device and catalysts, respectively. The optimum conversion rate of hydrogen was 84.11% when the reaction temperature was at 70 °C with 3%wt. Fe2O3/Al2O3 and the calcination temperature was 500 °C. The results showed that the catalytic performance of Fe2O3/Al2O3 is superior to Fe2O3. The selectivity of the reaction of hydrogen and chloride was higher than that of hydrogen and oxygen. We also characterized the catalysts with XRD, XPS, SEM and N2 adsorption-desorption and the results showed that the iron oxide was dispersive uniformly on the support surface.

A new demethyl abietane diterpenoid, Triptotin K (3) together with three known compounds, friedelin (1), canophyllal (2), and triptonoterpene (4) were isolated from the roots of Tripterygium wilfordii Hook. f. by silica gel column and preparative high performance liquid chromatography. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Triptotin K showed cytotoxic activities against KB, KBv200, HepG2, and MCF-7/ADM cells lines with IC50 values of 29.88, 36.50, 39.55, and 41.38 μM, respectively.

Methane explosion is studied with a 20-liter content, spheroidal explosion tank. Mixture of methane with oxygen at varied ratio is detonated in the enclosed tank while pressure inside the tank is real-time recorded during the experiments. Temperature and conversion rate of the methane inside the tank during the explosion is calculated according to actual gas equation of state and energy conservation equation. Kinetic equations of the explosion process are derived among conversion rate, species concentration and temperature. Kinetic parameters of the steadily accelerating phase of the explosion process, including the apparent equilibrium constant and enthalpy change, as well as activation energy and pre-exponential factor, are calculated based on kinetic equations and experimental data.

In this study, liquid oxy-nitriding (LON) at different temperatures (430 °C, 450 °C, 470 °C) was employed on the AISI H13 steel. Effects of LON on wear and molten aluminum corrosion of AISI H13 steel were investigated. LON treatments significantly improved wear resistance due to synergy between high-hardness nitriding layer and lubricating oxide film. Molten aluminum corrosion resistance was also improved, especially by LON 470 treatment. Fe3O4 film and nitriding layer on LON 470 transformed the corrosion mechanisms from dissolution into oxidation. Therefore, LON process may be a choice for combating the dissolution corrosion of liquid metals.