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(Ti/Zr/Hf)CoSb 0.8 Sn 0.2 compounds are promising p -type thermoelectric materials. In this work, excessive Ga and Co deficiencies were introduced into Ti 0.2 Hf 0.8 CoSb 0.8 Sn 0.2 compounds. The microstructure, electrical, and thermal transport properties were investigated in the temperature range of 300 K < T < 1000 K. The excessive Ga formed nanoinclusions with Ti and Sn at the grain boundaries. The Co deficiencies lowered the thermal conductivity and simultaneously improved the electrical conductivity. As a result, the power factor was enhanced to 3.2 mW/m K2, and the maximum Z.T. of ∼0.93 at 988 K was obtained in the Ti 0.2 Hf 0.8 Co 0.99 Sb 0.8 Sn 0.2 –0.01Ga sample, which is an increase of ∼48% compared to that of the pristine Ti 0.2 Hf 0.8 CoSb 0.8 Sn 0.2 sample. [ABSTRACT FROM AUTHOR]

[Display omitted] • N-N6A and N-N6B exhibit excellent properties exceeding the benchmark molecule HMX. • N-N6B features the highest density among the long-catenated nitrogen systems. • The nitroamide functionality may open a new venue for molecular design of HEDMs. Fully energetic functionalization of catenated nitrogen systems is highly challenging due to the lack of incorporation methodology. In this work, two catenated nitrogen N6 structures containing six nitro groups, i.e., (E)-1,1′-bis [5-Nitroamide-3,4-dinitro-1H-pyrazole] diazene (N-N6A) and its regioisomer (E)-1,1′-bis [4-Nitroamide-3,5-dinitro-1H-pyrazole] diazene(N-N6B) were designed and synthesized. Despite the same chemical formula and azo functionality, N-N6B exhibits better overall performance than N-N6A. Meanwhile, N-N6B has the highest density with excellent detonation performance (d = 1.94 g cm−3, Dv = 9440 m s−1, and P = 39.6 GPa) among the reported long-catenated nitrogen atom chains, indicating the potential for high energy materials. Particularly, as the precursors of N-N6A and N-N6B , the mechanical sensitivities of N6A and N6B (N6A , IS = 11 J, FS = 160 N; N6B , IS = 14 J, FS = 240 N) are apparently superior to that of literature long nitrogen-chains energetic material. The different performance of these compounds highlights the effect of the regioisomeric functionalization on designing advanced energetic materials. [ABSTRACT FROM AUTHOR]

This study reports an effective and facile strategy for developing multifunctional nanoplatforms by the in situ doping of manganese metal into stellate mesoporous silica nanoparticles (Mn-SMSN). The resulting Mn-SMSN@DOX-IR-780 effectively integrated enhanced chemodynamic therapy (CDT) combined with tumor imaging in a single platform after additional loading of doxorubicin hydrochloride (DOX) and IR-780 iodide (IR-780) onto Mn-SMSN. Mn-SMSN@DOX-IR-780 demonstrated excellent in vitro efficacy in killing cancer cells and inhibiting cancer cell migration and invasion. Further mechanistic investigations demonstrated that Mn-SMSN@DOX-IR-780 effectively promoted the production of cytotoxic reactive oxygen species to kill tumor cells. Moreover, Mn-SMSN@DOX-IR-780 efficiently delivered DOX and IR-780 into cells, indicating potential for chemodynamic therapy and tumor imaging. In summary, the developed Mn-SMSN@DOX-IR-780 integrated CDT and image guidance, which can provide insights for future biomedical research applications concerning efficient prostate cancer treatment. [Display omitted] • Mn-SMSN@DOX-IR-780 is developed by in situ doping of manganese metal into Mn-SMSN. • Chemodynamic therapy (CDT) is integrated with tumor imaging by Mn-SMSN@DOX-IR-780. • This is achieved by loading of doxorubicin hydrochloride and IR-780 iodide onto Mn-SMSN. • Mn-SMSN@DOX-IR-780 promoted cytotoxic reactive oxygen species to kill tumor cells. • CDT and image guidance integration can provide insights for prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia cytogenetics and molecular subtypes are connected with microRNAs, although it is unclear how miRNAs affect AML pathogenesis. miR-409–3p expression is downregulated in bone marrows, as we have previously demonstrated in our team. Nevertheless, the tumor-suppressing activities and molecular mechanisms of miR-409–3p remain unknown. Hence, in this study, we investigate at the functional significance of miR-409–3p in the development of AML. We found that a significant decrease in miR-409–3p expression was observed in THP-1 cell. The expression of miR-409–3p was altered in THP-1 by transfecting with agomiR-409–3p and agomiR-409–3p NC. A series of experiments showed that overexpression of miR-409–3p expression significantly suppressed proliferation and increased the apoptosis of THP-1. Moreover, Rab10 was confirmed as a direct target gene of miR-409–3p and was negatively modulated by miR-409–3p. Rab10 downregulation imitated the suppressed proliferation and increased the apoptosis of THP-1. Furthermore, miR-409–3p overexpression or Rab10 knockdown obviously down-regulated the expression levels of Bcl-2, but up-regulated Bax expression. In a xenograft mouse model, miR-409–3p-overexpressed THP-1 cells resulted in much less tumor weight and size in the mice bearing the cells as compared to the mock-transfected mice. Collectively, our findings demonstrated that miR-409–3p exerted tumor suppressor gene effects in AML by directly targeting Rab10, which might provide a promising therapeutic target for AML. [Display omitted] • miR-409–3p was downregulated and Rab10 was upregulated in THP-1 cells. • Rab10 was a target of miR-409–3p, and upregulation of miR-409–3p downregulated Rab10 mRNA and proteins levels. • miR-409–3p over-expression inhibited proliferation, promoted cell apoptosis, and inhibited AML tumor growth. • Rab10 knockdown inhibited proliferation and promoted apoptosis in THP-1 cells. • miR-409–3p inhibited the progression of AML via directly targeting Rab10. [ABSTRACT FROM AUTHOR]

Microorganism breeding is a known cause of food spoilage and disease transmission. Aspergillus niger ( A. niger ) and Bacillus subtilis ( B. subtilis ) are examples of microorganisms that cause deterioration of fresh fruits and vegetables during storage, which can be a serious threat to human health. In this work, we synthesized a self-assembled film of graphene oxide (GO) and chitosan (CS) biopolymers with titanium dioxide (TiO 2 ) nanoparticles embedded in its surface. We then characterized its antibacterial and preservative properties. We found that these non-cytotoxic nanometer-scale films, especially when the ratio of graphene oxide, chitosan and titanium dioxide nanoparticles in the nanocomposites is 1:20:4, exhibited high antibacterial activity against the biofilm-forming strains A. niger and B. subtilis . The preservation capacity of the nanocomposites was evaluated by enzymatic experiments. The nanocomposites did not show any cytotoxicity against mammalian somatic cells and plant cells. Altogether, this work demonstrated that the nanocomposites disrupted microbial film formation while avoiding internalization by animal and plant cells. Due to their selectivity and safety, these nanocomposites demonstrate potential as antimicrobial coatings for food preservation. [ABSTRACT FROM AUTHOR]

MicroRNA are non-coding small RNAs that bind to their target mRNA and cause mRNA degradation or translation inhibition. MiRNA dysregulation is linked to a variety of human cancers and has a role in the genesis and development of cancer pathology. MiR-328 has been reported to be involved in various human cancers. And miR-328 is considered a key regulator in human cancer. It participates in biological processes such as proliferation, apoptosis, invasion, migration, and EMT. The present review will combine the basic and clinical studies to find that miR-328 promotes tumorigenesis and metastasis in human cancer. And we will describe the diagnostic, prognostic, and therapeutic value of miR-328 in various human cancers. [Display omitted] • MiR-328 is differentially expressed in different types of cancer. • MiR-328 can target multiple different genes to regulate the biological functions of cancer cells. • MiR-328 can be regulated by lncRNAs and circRNAs and participates in multiple signaling pathways. • Targeting miR-328 could be a novel strategy for the diagnosis and treatment of cancer. [ABSTRACT FROM AUTHOR]

Hydrogen production from electrochemical water splitting is a promising strategy to generating green energy, which requires development of efficient and stable bifunctional catalysts for hydrogen and oxygen evolution reaction (HER/OER). Herein, dual transition metal phosphides/N-doped carbon/Nickel foam composite (CoNiP/NC-NF) is prepared via direct phosphidation of ZIF-67, in which ZIF-67 can control the size and N-doping content of CoNiP/NC, boosting the bifunctional activities for the OER and HER. Then, the overall water splitting is performed by using CoNiP/NC-NF as the cathode and anode, showing a low cell voltage of 1.60 V to reach current density of 10 mA cm−2. Experimental studies indicate that ZIF-67 influences the electrocatalytic performance, and theoretical studies identify the active component of CoNiP/NC-NF for HER and OER, respectively. [Display omitted] • ZIF-67 based TMPs were prepared with good activities for the OER and HER. • The overall water splitting was applied using this material as the cathode and anode. • ZIF-67 influenced the electrocatalytic performance of OER and HER. [ABSTRACT FROM AUTHOR]

Abstract: Novel Eu2+-doped Ca2AlSi3O2N5 phosphors with a general formula of Eu x Ca2−x AlSi3O2N5 were successfully prepared via a solid-state reaction method under a nitrogen atmosphere. The produced phosphors were effectively excited by UV–vis light in the wavelength range between 250 and 400nm, and featured an intense green emission band which peaked at about 500nm. The emission spectra featured a red-shift over increasing Eu2+ content and the temperature of heat treatment. The maximum intensity of emission was obtained for x =0.014 and heat treatment at 1450°C. The photoluminescence properties of the produced Ca2AlSi3O2N5:Eu2+ phosphors qualify them for consideration in potential use as green phosphors in UVLED-based white LED. [Copyright &y& Elsevier]

Abstract: In this article, a rapid and cost-effective melt spinning (MS) subsequently combined with a spark plasma sintering (SPS) process was utilized to prepared n-type Bi2(Te1−x Se x )3 (x = 0.0–1.0) solid solutions from high purity single elemental chunks. The substitution of tellurium by selenium has significant impacts on the electrical and thermal transport properties of the Bi2(Se x Te1−x )3 compounds in a manner which can be well understood using a valence bond rule and the corresponding change in band gap. Furthermore, the selenium substitution effectively adjusts the carrier density allowing an optimum value of ∼5 × 10−19 cm−3. As a result, a maximum ZT of 1.05 at 420 K was achieved for the Bi2(Se0.2Te0.8)3 sample which also shows an improved average ZT of ∼0.97 in the entire measurement temperature range. By adopting the same p-type legs, the module fabricated by the MS-SPS Bi2(Se0.2Te0.8)3 material which acts as n-type legs shows ∼10% enhancement in thermoelectric conversion efficiency compared with the module fabricated by n-type zone melted ingots. [Copyright &y& Elsevier]

Abstract: Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson''s disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10μM significantly increased DAT mRNA levels by 54–130% in 4–8h, VMAT2 mRNA levels by 34% in 4h, and Nurr1 mRNA levels by 31–39% in 2–4h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn’t show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor. [Copyright &y& Elsevier]

We introduce a new topology-preserving 3D thinning procedure for deriving the curve voxel skeleton from 3D binary digital images. Based on a rigorously defined classification procedure, the algorithm consists of sequential thinning iterations each characterized by six parallel directional sub-iterations followed by a set of sequential sub-iterations. The algorithm is shown to produce concise and geometrically accurate 3D curve skeletons. The thinning algorithm is also insensitive to object rotation and only moderately sensitive to noise. Although this thinning procedure is valid for curve skeleton extraction of general elongated objects, in this paper, we specifically discuss its application to the orientation modeling of trabecular biological tissues. [Copyright &y& Elsevier]

[Display omitted] • Battery-grade FePO 4 ·2H 2 O was prepared by copper slag resource utilization. • FePO 4 ·2H 2 O was synthesized by selective sediment in the leachate. • Adding Na 2 HPO 4 ·12H 2 O without extra pH adjustment. • The battery performance of synthetic LFP/C is effective. • Life cycle assessment indicates that the technology is environmentally friendly. Copper slag (CS) contains a high content of valuable iron, the stockpile of CS occupies a large amount of land and leads to a waste of secondary resources. This study proposed producing battery-grade FePO 4 ·2H 2 O from CS through selective leaching, synthesis, and purification. The combined acid leaching/evaporation method was used to leach out Fe and inhibit Si from fayalite selectively, and then FePO 4 ·2H 2 O was formed by adding Na 2 HPO 4 ·12H 2 O without extra pH adjustment. The purity of FePO 4 ·2H 2 O obtained by using a reactor heated for 5 h at 180 ℃ with an HCl concentration of 2.5 M was 99.47 %, and the impurities were all by the industry standard for battery-grade FePO 4 ·2H 2 O (HG/T 4701–2021). The LiFePO 4 /C material was further synthesized and tested for battery performance. Under the test current of 0.1C, the charging-specific capacity of the battery in the first week was 175.8 mAh/g, and the discharge-specific ability was 159.3 mAh/g, which was close to the theoretical specific capacity and effective. Life cycle assessment (LCA) indicated that for each 1 kg of iron phosphate produced, the carbon emission of this study was reduced by 4.71 kg CO 2 eq compared with the traditional technology. [ABSTRACT FROM AUTHOR]

Layered TiS 2 is of great potential in thermoelectrics for room temperature and medium temperature applications due to its tunable transport properties, low environmental impact, low cost, and lightweight. Herein, we prepared Fe x TiS 2– δ with x varying from 0 to 0.05 through a two-step process, involving initial synthesis in sealed tubes followed by spark plasma sintering. Mössbauer spectroscopy indicated that Fe atoms occupy the octahedral sites in the van der Waals gaps and exist in the form of Fe2+ with a high spin state. Fe x TiS 2– δ with x ≤ 0.02 exhibit high in-plane power factors, reaching an average of ∼ 1.2 mWm–1K–2. The structural disorder caused by Fe intercalation leads to a significant decrease in out-of-plane lattice thermal conductivity. The anisotropy in the figure of merit, ZT , of Fe x TiS 2– δ is suppressed due to Fe intercalation. Fe 0.01 TiS 2– δ possesses the highest ZT of 0.39 at 625 K along the in-plane direction. [ABSTRACT FROM AUTHOR]

• Our study is firstly to investigate the effect of Clostridium butyricum on structure and composition of gut microbiota and also explore the its effect on suppression of proinflammatory cytokines and NF-κB pathway by which reduced colitis associated colon cancer in mice. • We also explore the effect of Clostridium butyricum on expression of proinflammatory cytokines such as TNF-a, IL-6 and enzyme COX-2 and to explore whether Clostridium butyricum can promote apoptosis of colorectal cancer cells by blocking the activation of Nuclear Factor-kappa B (NF-κB) pathway. • We find that CB could regulate structure and composition of gut microbiota and reduces colitis associated colon cancer in mice, the mechanism may be inhibiting NF-κB pathway and promoting apoptosis. We investigate the effects of Clostridium butyricum(CB) on gut microbiota and colitis associated colon cancer(CAC) in mice.6–8 weeks old C57BL/6 mice were randomly divided into control, azoxymethane (AOM) + dextran sodium sulphate (DSS) and AOM + DSS + CB groups. Mice in the latter two groups received an intraperitoneal injection of AOM (12.5 mg/kg), followed by three cycles of DSS diluted in water (2.5% w/v). Mice in treatment group received CB (2 × 108 CFU in 200 ul normal saline) by gavage administration three times one week. Microbiota composition was assessed by 16S rRNA high-throughput sequencing. Colon samples were collected to examine severity of colitis and tumorigenesis. Cytokines including TNF-a, IL-6 and Cyclo-oxygenase-2 (COX-2) were detected by RT-qPCR. Expression of Bcl-2, Bax and the state of components of NF-κB signaling pathway were detected by western blot. The results revealed that CB regulated structure of intestinal flora and changed the microbial composition; decreased Firmicutes/ Bacteroidetes ratio in phylum level and increased the relative abundance of probiotics; decreased colitis, decreased incidence and size of colorectal cancer(CRC) and increased apoptosis of tumor cells; decreased cytokines including TNF-a and IL-6; decreased level of COX-2; decreased phosphorylation of NF-κB; decreased level of Bcl-2 and increased expression of Bax. In conclusion, CB could regulate structure and composition of gut microbiota and reduces colitis associated colon cancer in mice, the mechanism may be inhibiting NF-κB pathway and promoting apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Mn2+–Ce3+ co-doped MgYSi2O5N phosphors were prepared by a solid-state reaction method. Their photoluminescence properties were studied in terms of absorption, excitation, and emission spectra. They could be effectively excited by ultraviolet light and showed intense blue and red emissions, making them attractive candidate phosphors for white light LED application. The luminescence of Ce3+ significantly increased with the incorporation of Mn2+ and an efficient energy transfer from Ce3+ to Mn2+ ions occurred. The blue band emission was attributed to the 5d1–4f1 transition of Ce3+ ions, and the double red band emission was attributed to the single Mn2+ ion and Mn2+ pairs or clusters. The effects of Ce3+ and Mn2+ concentrations on luminance have also been studied. [Copyright &y& Elsevier]

Co-substitution of Eu and Nb into insulating CaTiO 3 can make it a good n-type potential thermoelectric (TE) material. In the present work, solid solution compounds with the nominal composition Ca 0.8 Eu 0.2 Ti 1– x Nb x O 3– δ (x = 0.05, 0.08, 0.1, 0.12) were synthesized and sintered in different atmospheres, including argon (Ar) and forming gas (5 vol% H 2 in Ar). Notably, the different reduction effects of these atmospheres resulted in significant differences in phase formation, grain size, oxygen deficiency, and TE properties of the synthesized samples. Introducing additional electrons to the system by donor substitution of Ti with Nb leads to significant changes in the electrical conductivity and Seebeck coefficient. The most favorable TE performance of the prepared samples was found in the sample with x = 0.05, primarily attributed to its proper charge carrier concentration. This work highlights the crucial role of the sintering atmosphere in manipulating the TE performance of n-type CaTiO 3 -based ceramics, an effect similar to donor doping. [Display omitted] • Sintering atmospheres play a vital role in determining thermoelectric transport properties of titanate perovskites. • Nb is an efficient electron donor in the titanate perovskite system. • Tungsten carbide impurity can significantly enhance the thermal conductivity. [ABSTRACT FROM AUTHOR]

Abstract Oxide materials are of current interest as high-temperature thermoelectrics in the automotive and manufacturing energy-harvesting sectors due to high chemical robustness, low toxicity and low cost. Driven by a need to improve the thermoelectric performance of n-type oxides to the level of p-type analogues, ceramics and composites based on donor-doped SrTiO 3 are considered as a promising material. Here Nb-doped SrTiO 3 with Nb content of 10 and 15% as well as Sr/(Nb + Ti) ratio of 1.00 and 0.98 was mixed with 0.6 wt. % of graphene oxide (GO) prepared by Hummer-based method and conventionally sintered in atmosphere of H 2 /N 2 to reduce both Nb-doped SrTiO 3 and GO. Addition of reduced GO in combination with introduction of Sr vacancies provides a synergistic effect of fastening charge transport and thereby increasing electrical conductivity σ and suppressing the thermal conductivity κ. These factors, together with a moderate Seebeck coefficient S , result in a high power factor PF = S 2 × σ up to ∼1.98 mW/(K2m) and thermoelectric figure of merit ZT = PF × T / κ up to 0.29. These findings offer further prospects for seeking high performance SrTiO 3 -based thermoelectrics by modification with reduced GO. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Transfusion-related acute lung injury (TRALI) is the infusion of blood or blood system. To explore the mechanism of TLR4-mediated T cell immune effect in TRALI. In this animal study, a mouse model of LPS-induced TRALI was established. Sixty adult C57/BL6 mice (wild-type, WT) were randomly divided into 5 groups: 1) normal WT type, 2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody) TRALI group (LPS + MHC-I mAb). Mice were injected with LPS (0.1 mg/kg) and MHC-I mAb (2 mg/kg) into the tail vein. H&E staining was performed to detect pathological features. The myeloperoxidase (MPO) activity and the level of inflammatory cytokines in lung tissue homogenate supernatant were measured. Blood, spleen single-cell suspension, and bronchoalveolar lavage fluid were collected to detect the ratio of Treg and Th17 cells by flow cytometry. RT-PCR and WB were used to detect mRNA or protein expression. TLR4 mAb treatment alleviated the pathogenesis of LPS-induced TRALI in vivo, the MPO activity, and the level of proinflammatory factors in lung tissues. TLR4 exerted its function by changing of Treg/Th17 ratio via the SLIT2/ROBO4 signaling pathway and downregulating CDH5 and SETSIP. TLR4 mediates immune response in the LPS-induced TRALI model through the SLIT2/ROBO4 signaling pathway. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MC-LR) is the most common and toxic hepatotoxin and it could induce human hepatitis and hepatocellular carcinoma (HCC) via the route of drinking water. The aim of the present study was to determine the expressions of oncogenes c - fos , c - jun , c - myc , c - met , and N - ras and tumor suppressor gene PTEN in HepG2 cells following MC-LR-exposure to understand the possible mechanism of MC-LR-related human primary liver cancer. The results of qPCR and Western blotting showed that MC-LR-exposure at non- or sub-cytotoxic concentrations promoted the expressions of oncogenes c - fos , c - jun , c - myc , c - met , and N - ras while suppressed tumor-suppressor gene PTEN in HepG2 cells at both transcription and protein levels. This result suggests that HCC-related genes may be involved in human hepatitis and primary liver cancer caused by MC-LR. The work might be useful for evaluating the human health risk resulted from the long-term of MC-LR-exposure at low dose via drinking water route. [ABSTRACT FROM AUTHOR]

• This paper designs a fusion algorithm based on the biological rattlesnake vision imaging mechanism. • This paper introduces the rattlesnake bimodal cell working mechanism to design the visual neural network structure. • This paper introduces the mathematical model of the rattlesnake bimodal cell working mechanism. • This paper further improves the visual neural network structure to better simulate the fusion mechanism of the rattlesnake. In this paper, on the basis of the rattlesnake visual receptive field mathematical model and bimodal cell mechanism, a pseudo color image fusion visual neural network structure is designed. The visual neural network structure is composed of three stages. The first stage performs six bimodal cell fusion of source images, obtaining the six fusion signals. The second stage divides the six fusion signals into three groups, obtaining the enhanced signals such as X 1 , X 2 , X 3 , X 4 , X 5 and X 6 by feeding the fusion signals into the center or surrounding area of the ON-opponent system and OFF-opponent system. The third stage feeds the X 1 , X 3 and X 5 into the center excitation area, and the X 2 , X 4 and X 6 into the surround inhibition area of the ON-opponent system. The results are then mapped to the three channels of B, G and R in turn, obtaining the fusion image. The experimental results show that the image fusion method has superior performance. The fusion image has superior performance in subjective visual evaluation. In terms of objective quality evaluation, the four evaluation indicators of entropy (EN), average gradient (AG), spatial frequency (SF), and standard deviation (SD) are higher than the experimental results of related literature. [ABSTRACT FROM AUTHOR]

Midbrain dopamine (DA) neurons are involved in cognition, control of motor activity, and emotion-related behaviors. Degeneration of DA neurons particularly in the substantia nigra is a hallmark of Parkinson's disease. The homeobox transcription factor, Pitx3, plays a critical role in the development, function, and maintenance of midbrain DA neurons. We found that in young adult Pitx3-null mice, Pitx3(−/−), there was decreased tyrosine hydroxylase staining, indicating a loss of DA neurons particularly in the substantia nigra. In addition, fast-scan cyclic voltammetry and microdialysis assays of DA release indicated that the lack of Pitx3 caused a significant reduction of striatal DA release. Tonic DA release was impaired more significantly than the phasic DA release induced by burst firing of DA neurons. Furthermore, behavioral tests revealed that Pitx3(−/−) mice displayed abnormal motor activities, including impaired motor coordination and decreased locomotion. In summary, these data provide further evidence that Pitx3 is specifically required for DA-related function and, if impaired, Pitx3 could contribute during the pathogenesis of Parkinson's disease. [ABSTRACT FROM AUTHOR]

The design of two-dimensional (2D) heterostructures (HSs) is an effective method to tune the physical and chemical properties of 2D materials. Using first-principles calculations, we explore the photocatalytic activity of CdS/PtSSe HSs (CPHSs) including CdS/SPtSe HSs (CPHS(S)s) and CdS/SePtS HSs (CPHS(Se)s). The small lattice mismatches and the negative interface formation energies suggest that the CPHSs are feasible, and the small bandgaps guarantee the CPHSs to absorb sufficient visible light. The stacking configurations can hardly affect the electronic structures of CPHS(S)s and CPHS(Se)s, but the contact sides can switch CPHSs between type-I and type-II. The type-I CPHS(Se)s are potential candidates as light-emitting diodes. For the CPHS(S)s, the type-II band alignments promote the spatial separation of photogenerated carriers, and the induced built-in electric fields around the interface region also promote the separation of photoinduced carriers. In addition, the band edges of CPHS(S)s fulfill the thermodynamic requirements for photocatalytic water-splitting, and the solar-to-hydrogen efficiencies are up to 37.5%. All these factors prove the CPHS(S)s are highly efficient photocatalysts to split water. [Display omitted] • The electronic, optical, and photocatalytic properties of 2D CdS/PtSSe heterostructures are studied. • The CdS/PtSSe heterostructures could switch between type-I and type-II by the change of contact sides. • The CdS/SPtSe heterostructures are promising water-splitting photocatalysts with the solar-to-hydrogen efficiency of 37.5%. [ABSTRACT FROM AUTHOR]

Cancer cells are typically characterized by abnormal quality control of mitochondria, production of reactive oxygen species (ROS), dysregulation of the cell redox state, and the Warburg effect. Mutation or depletion of PTEN-induced kinase 1 (PINK1) or Parkin leads to mitophagy defects and accumulation of malfunctioning mitochondria, and is often detected in a variety of tumors. However, PINK1's role in the progression of gastric cancer (GC) remains unclear, with its main effect being on mitochondrial turnover, metabolic reprogramming, and tumor microenvironment (TME) alteration. To address these issues, we first assessed the expression levels of PINK1, mitophagy-associated molecules, ROS, HIF-1α, glycolysis-associated genes, and macrophage signatures in GC tissues and matched tumor-adjacent normal samples. In addition, GC cell lines (AGS and MKN-45) and xenograft mouse models were used to determine the mechanism by which PINK1 regulates mitophagy, metabolic reprogramming, tumor-associated macrophage (TAM) polarization, and GC progression. We found that PINK1 loss correlated with advanced stage GC and poorer overall survival. GC tissues with lower PINK1 levels showed compromised mitophagy signaling and enhanced glycolytic enzyme expression. In vitro experiments demonstrated that PINK1 deficiency promoted GC cell proliferation and migration through the inhibition of mitophagy, production of mitochondrial ROS, stabilization of HIF-1α, and facilitation of the Warburg effect under both normoxic and hypoxic conditions. Moreover, PINK1 deficiency in GC cells promoted TAM polarization toward the M2-like phenotype. Reintroduction of PINK1 or inhibition of HIF-1α effectively repressed PINK1 deficiency-mediated effects on GC cell growth, metabolic shift, and TAM polarization. Thus, mitophagy defects caused by PINK1 loss conferred a metabolic switch through accumulation of mtROS and stabilization of HIF-1α, thereby facilitating the M2 polarization of TAM to remodel an immunosuppressive microenvironment in GC. Our results clarify the mechanism between PINK1 and GC progression and may provide a novel strategy for the treatment of GC. [ABSTRACT FROM AUTHOR]

Ceramic SiCN nanocomposites modified with nanocellulose derived defect-rich carbon nanofibers (CNFs-SiCN) were developed by thermolysis of nanocelulose-polysilazane single-source precursors (SSPs). Multi-loss mechanisms (i.g. polarization loss and conductive loss) were established in the SiCN ceramic nanocomposites by employing the defect-rich structure of CNFs. Cole-Cole circle plots indicate that the CNFs-SiCN ceramics possess strong polarization capability due to the defect-rich structure of the CNFs. Dielectric loss values fitted by the Debye theory showed that the proportion of polarization loss reaches an unprecedented high value, accounting for 52.1% of the total dielectric loss. When the content of nanocellulose is 10 wt% of SSPs, the minimal reflection coefficient (RC min) and effective absorption bandwidth (EABs) of CNFs-SiCN ceramic can reach −36.3 dB and 3.0 GHz, respectively. This work may contribute new ideas for establishing multi-loss mechanisms in ceramic-based materials, finding a new application for nanocellulose, and shaping the design of novel absorbents. [Display omitted] [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is a significant risk factor for development of gastric cancer (GC), one of the deadliest malignancies in the world. However, the mechanism by which H. pylori induces gastric oncogenesis remains unclear. Here, we investigated the function of IL-6 in gastric oncogenesis and macrophage-epithelial cell interactions. We analyzed publicly available datasets to investigate the expression of IL-6 and infiltration of M2 macrophages in GC tissues, and determine the inter-cellular communication in the context of IL-6. Human gastric epithelial and macrophage cell lines (GES-1 and THP-1-derived macrophages, respectively) were used in mono- and co-culture experiments to investigate autocrine-and paracrine induction of IL-6 expression in response to H. pylori or IL-6 stimulation. We found that IL-6 is highly expressed in GC and modulates survival. M2 macrophage infiltration is predominant in GC and drives an IL-6 mediated communication with gastric epithelium cells. In vitro , IL-6 triggers its own expression in GES-1 and THP-1-derived macrophages cells. In addition, these cell lines are able to upregulate each other's IL-6 levels in an autocrine fashion, which is enhanced by H. pylori stimulation. This study indicates that IL-6 in the tumor microenvironment is essential for intercellular communication. We show that H. pylori enhances an IL-6-driven autocrine and paracrine positive feedback loop between macrophages and gastric epithelial cells, which may contribute to gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that activates the transcription of genes and is responsible for progression of cell survival and proliferation. The synthesis of HIF-1α can be stimulated via oxygen (O2)-independent mechanisms; whereas, the degradation of HIF-1α is regulated via Fe2+ and/or O2-dependent enzyme prolyl hydroxylase (PHD). Aberrant iron accumulation, mitochondrial dysfunction and impairment of protein degradation system, such as autophagy, have been implicated in the pathogenesis of Parkinson''s disease, among which, iron and mitochondrial dysfunction may enhance the enzyme activity of prolyl hydroxylase and cause the decrease of HIF-1α. Recent reports have indicated that HIF-1α may induce autophagy under hypoxic condition. Considering the metabolic characteristics of HIF-1α under the pathogenesis of Parkinson''s disease, we speculated that compounds that might stabilize HIF-1α could prevent neuronal injury caused by excessive iron or mitochondrial injury under normoxic condition. Deferoxamine is one of iron chelators that may accumulate HIF-1α due to the decreased degradation of HIF-1αvia inhibition of prolyl hydroxylase activity. In this study, we showed that the protein level of HIF-1α was decreased in rotenone or MPP+-treated SH-SY5Y cell models of Parkinson''s disease. We demonstrated that deferoxamine caused accumulation of HIF-1α accompanied by the enhancement of autophagy in SH-SY5Y cells. When HIF-1α gene was inhibited, deferoxamine-induced autophagy was suppressed accordingly, indicating that deferoxamine-induced autophagy was dependent on the expression of HIF-1α. Our results also showed that deferoxamine attenuated rotenone-induced apoptosis, which was blocked when HIF-1α or autophagy related gene Beclin 1 was suppressed. In summary, the present study indicated that the level of HIF-1α was decreased under the situation when mitochondrial complex I was inhibited, and the neuroprotective role of deferoxamine in rotenone-induced apoptosis could be partially explained by its effects on the accumulation of HIF-1α and HIF-1α-mediated induction of autophagy. [Copyright &y& Elsevier]

Abstract: The catalytic cracking of a high density hydrocarbon fuel, tricyclo [5.2.1.02.6] decane (JP-10) over HZSM-5 molecular sieves with different Si/Al mole ratios of 25, 38, and 50 was investigated at the temperature range from 773 to 873K. Compared with the thermal cracking and the catalytic cracking over ZSM-5, conversions of JP-10 from the catalytic cracking over HZSM-5 molecular sieves at the same temperature were evidently heightened. The predominant hydrocarbon products from the catalytic cracking, checked at room temperature and atmospheric pressure, were methane, ethane, ethene, propane and propylene in the gaseous phase and benzene, indene, naphthalene and their homologues in the liquid phase. The contents of ethane, propane and propene decrease with increasing Si/Al mole ratio of a catalyst while those of methane and ethene increase simultaneously with the increase of Si/Al mole ratio of HZSM-5. The contents of the main components in the liquid products produced on the catalyst surface at a given temperature also decreased with the increase of Si/Al mole ratio. To keep high yields of alkenes, the HZSM-5 catalyst with high Si/Al mole ratio could be chosen. [Copyright &y& Elsevier]

A novel and sustainable paper template-based method was developed for the fabrication of advanced niobium carbide (NbC)-based free-standing films for electromagnetic interference (EMI) shielding application. Through employing the porous structure of paper template, the simultaneous optimization of thickness, flexibility, density and shielding effectiveness (SE) of NbC-based films was facilely achieved. The pyrolytic carbon (PyC) derived from paper worked as a carbon source for the growth of the NbC phase. A hierarchically porous structure with a porosity of ∼80 vol % was established to optimize the flexibility and density of the resultant films. Adjusted heterogeneous NbC-PyC nano-interfaces were formed by controlling the amount of NbC and the remaining PyC phase in the films, which significantly improved the absorption capability of EM waves. At the highest NbC content, the film possesses shielding effectiveness of 50 and 86 dB when the sample thickness is ∼55 and ∼220 μm, respectively compared to 32 dB of pristine paper-derived PyC film (∼55 μm). These results provide guidance to explore more eco-friendly and commercially effective routes for the recycling of used paper through developing their application in the EM field. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Bimetallic Co-Ni catalysts were firstly developed by a molecular-level engineering strategy. • The superior performance of bimetallic catalysts is unprecedentedly pinpointed via DFT calculations. • The specific yields of carbon nanocomposites and H 2 are outstanding compared to the reported work. • The carbon nanocomposites exhibited excellent electromagnetic absorption performance. The advancement in the pyrolysis-catalysis conversion of waste plastics is currently limited by three problematic issues, namely lack of efficient catalysts, ambiguous catalytic mechanism, and identification of a dedicated application of carbon nanocomposites. Herein, advanced bimetallic NiCo/MnO catalysts were developed via a molecular- and macroscale-level engineering strategy. The best conversion performance among all batches was achieved for a Co:Ni molar ratio of 1:1. When the plastic-to-catalyst ratio is 10.7:1, the H 2 and carbon yields of polyethylene conversion reached 29.8 mmol/g plas and 42.2 wt%, respectively. Density functional theory simulations rationalized the activity of NiCo/MnO catalysts in the dehydrogenation of hydrocarbons. The resulting carbon nanocomposites demonstrated excellent electromagnetic absorption performance with an effective absorption bandwidth of the representative carbon nanocomposites/wax composite of 5.12 GHz and a minimal reflection loss lower than −45 dB. This work provides novel insights for developing advanced catalysts for the pyrolysis-catalysis conversion of waste plastics. [ABSTRACT FROM AUTHOR]

Orbital hybridization is a powerful tool for modulating electronic structures toward various electrocatalytic reactions. Compared to the widely reported d - d hybridization in d -block metal alloys, the p - d orbital hybridization between d -block metals and p -block elements could provide new opportunities for regulating the electronic properties and thus promoting the electrocatalytic activities. Herein, we report a distinctive p -block metalloid-regulating p - d orbital hybridization to realize the fabrication of RuSb nanobranches for bifunctional hydrogen evolution (HER) and hydrazine oxidation (HzOR), which exhibits huge potential in overall hydrazine splitting (OHzS) by utilizing thermodynamically favorable HzOR instead of sluggish oxygen evolution on the anode. To our delight, RuSb delivers an impressively low overpotential of 39 mV for HER and 252 mV for HzOR at 10 mA cm−2 in alkaline seawater. The two-electrode OHzS electrolyzer with RuSb||RuSb couple can achieve outstanding electrocatalytic activity with an extraordinarily small cell voltage of 35 mV to drive 10 mA cm−2 in alkaline seawater, outperforming the Pt/C||Pt/C couple under the same condition. Density functional theory calculations further indicate that the Sb doping can not only mediate the adsorption energy for hydrogen but also the energy barrier for the dehydrogenation of *N 2 H 3. Therefore, our work verifies the huge potential of p - d orbital hybridization for the development of a bifunctional OHzS system in alkaline seawater. [Display omitted] • p -block metalloid-regulating p - d orbital hybridization was proposed. • RuSb nanobranch for bifunctional HER and HzOR was achieved. • Small cell voltage in alkaline seawater was achieved. • Optimized hydrogen adsorption and energy barrier for dehydrogenation were confirmed. [ABSTRACT FROM AUTHOR]

Waste plastics and electromagnetic radiation pollution have been two serious issues that largely affect our environment. How to solve them in a single approach is a social and scientific challenge. In this work, advanced Co/MnO@carbon nanotube composite (Co/MnO@CNTs) absorbents were prepared via pyrolysis-catalysis conversion of face masks as post-consumer plastic waste with multi-scale designed Co x Mn 3– x O 4 spinel pre-catalysts. The (nano)structure (e.g., MnO-carbon and Co-carbon hetero-interface), composition, and graphitic degree of the Co/MnO@CNTs absorbents were facilely controlled by varying the catalytic reaction temperature and the composition of spinel pre-catalysts. By constructing multi-loss mechanisms (e.g., magnetic loss, conductive loss, interface polarization loss, and defects-induced polarization loss), the largest effective absorption bandwidth (EAB) of the Co/MnO@CNTs/wax composites can reach as wide as 5.28 GHz at a thickness of 1.7 mm. When the content of the Co/MnO@CNTs absorbents is 17 wt%, the EAB and minimal reflection loss (RL min) achieves 5.04 GHz and −38.1 dB, respectively. This work is based on a sustainable and cost-effective feedstock as well as an innovative method for the large-scale production of advanced CNTs-based materials in electromagnetic absorption application. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract This work aims to explore zirconium as a possible dopant to promote thermoelectric performance in bulk ZnO-based materials, both within the single-doping concept and on simultaneous co-doping with aluminum. At 1100–1223 K mixed-doped samples demonstrated around ∼2.3 times increase in ZT as compared to single-doped materials, reaching ∼0.12. The simultaneous presence of aluminum and zirconium imposes a synergistic effect on electrical properties provided by their mutual effects on the solubility in ZnO crystal lattice, while also allowing a moderate decrease of the thermal conductivity due to phonon scattering effects. At 1173 K the power factor of mixed-doped Zn 0.994 Al 0.003 Zr 0.003 O was 2.2–2.5 times higher than for single-doped materials. Stability tests of the prepared materials under prospective operation conditions indicated that the gradual increase in both resistivity and Seebeck coefficient in mixed-doped compositions with time may partially compensate each other to maintain a relatively high power factor. [ABSTRACT FROM AUTHOR]

Abstract Alzheimer's disease (AD) is a neurodegenerative disease with a complex pathogenesis. Controlled release, target ability, and multi-channel synergistic treatment are key factors associated with the success of AD drugs. Herein, we report a novel mesoporous nano-selenium (MSe) release delivery system (MSe-Res/Fc-β-CD/Bor) based on the borneol (Bor) target, β-cyclodextrin nanovalves (Fc-β-CD) with loaded resveratrol (Res). Previous experiments have shown that MSe-Res/Fc-β-CD/Bor first releases Bor by interacting with blood or intracellular esterases, allowing the nanosystem to pass through the blood-brain barrier (BBB). Subsequently, the Fc-β-CD is opened by the redox (H 2 O 2) response to the release of Res at the lesion site. We demonstrated that MSe-Res/Fc-β-CD/Bor inhibited aggregation of β-amyloid proteins (Aβ), mitigated oxidative stress, and suppressed tau hyperphosphorylation, while protecting nerve cells and successfully improving memory impairment in APP/PS1 mice. Interestingly, compared with rivastigmine (Riv) positive drugs alone, the MSe/Fc-β-CD/Bor loaded with Riv had a better pharmacokinetic index. These results indicate that MSe-Res/Fc-β-CD/Bor could be a prospective drug for treating AD. [ABSTRACT FROM AUTHOR]

In this work, multiscale designed 3-dimensional (3D) rose-like Co x Mn 3– x O 4 spinel smart pre-catalysts that can self-convert into the targeted active site-rich Co/MnO catalysts were developed for the high-efficiency conversion of waste plastics. At a pre-catalyst to plastic weight ratio of 1:14, the carbon nanotube composites (CNCs) and H 2 yield can reach 41 wt% and 36 mmol·g˗1 pla. , while the specific CNCs and H 2 yield can be as high as 7.48 g˗1 cat. and 634 mmol·g˗1 pla. ·g˗1 cat. The latter is more than one order of magnitude higher than reported in the literature. Density functional theory calculations indicate that the Co/MnO catalyst exhibits excellent activity in the dissociation of alkanes (e.g., CH 4). The resulting CNCs demonstrated excellent discharge capability and extended cycling performance when used as a lithium-ion battery anode. This work revealed an innovative recipe and novel insight for developing advanced catalyst materials as the next generation catalysts for the conversion of waste plastics. [Display omitted] • Self-conversion of multiscale designed smart pre-catalysts into active-site-rich Co/MnO catalysts to recycle waste plastics. • The physical mechanism of superior catalytic performance of Co/MnO is pinpointed via DFT calculation. • The specific carbon nanotube composites and H 2 yield of the Co/MnO catalyst reach a new record high. • The plastic converted carbon nanotube composites were tested to be excellent anode materials for lithium-ion batteries. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5 A, both FACS panels are identical and in Fig 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors' unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) Z-scheme photocatalytic systems can usually achieve high catalytic efficiencies by separating the photoinduced carriers attend water redox reaction at different positions and providing much stronger overpotentials to drive water redox reaction. However, it is filled with challenges to develop Z-scheme photocatalysts (PCs) due to the strict requirement of proper band edge alignment and built-in electric field. Based on hybrid density functional, the photocatalytic properties of CdO/PtSSe heterojunctions (HJs) including CdO/SPtSe and CdO/SePtS HJs are investigated. The analysis of electronic structures, work functions, and charge transfer suggest the proper band alignments and the existence of built-in electric field from CdO to PtSSe, confirming the Z-scheme photocatalytic mechanism of CdO/SPtSe and CdO/SePtS HJs. The light absorption curves show that CdO/SPtSe and CdO/SePtS HJs could harvest sufficient solar light. Furthermore, both CdO/SPtSe and CdO/SePtS HJs can provide sufficient overpotentials to finish water redox reaction. These findings indicate that CdO/SPtSe and CdO/SePtS HJs are promising water-splitting PCs. • The small bandgaps promote the CdO/SPtSe and CdO/SePtS HJs to utilize sufficient solar light. • Both CdO/SPtSe and CdO/SePtS heterojunctions are both direct Z-scheme photocatalysts. • The heterojunctions could provide sufficient driving force to finish the HER and OER processes. [ABSTRACT FROM AUTHOR]

Partial substitution of cations and anions in perovskite-type materials is a powerful way to tune the desired properties. The systematic variation of the cations size, the partial exchange of O 2− for N 3− and their effect on the size of the optical band gap and the thermal stability was investigated here. The anionic substitution resulted in the formation of the orthorhombic perovskite-type oxynitrides Mg 0.25 Ca 0.65 Y 0.1 Ti(O,N) 3 , Ca 1- x Y x Zr(O,N) 3 , and Sr 1– x La x Zr(O,N) 3 . A two-step synthesis protocol was applied: i) (nano-crystalline) oxide precursors were synthesized by a Pechini method followed by ii) ammonolysis in flowing NH 3 at T = 773 K (Ti) and T = 1273 K (Zr), respectively. High-temperature synthesis of such oxide precursors by solid–state reaction generally resulted in phase separation of the different A -site cations. Changes of the crystal structures were investigated by Rietveld refinements of the powder XRD data, thermal stability by DSC/TG measurements in oxygen atmosphere, oxygen and nitrogen contents by O/N analysis using hot gas extraction technique, and optical band gaps by photoluminescence spectroscopy. By moving from Mg 0.25 Ca 0.65 Y 0.1 Ti(O,N) 3 via Ca 1– x Y x Zr(O,N) 3 to Sr 1– x La x Zr(O,N) 3 , the degree of tilting of the octahedral network is reduced, as observed by an increase in the B – X – B angles caused by the simultaneously increasing effective ionic radius of the A -site cation(s). In general, increasing substitution levels on the A -site (Y 3+ and La 3+ ) are accompanied by an enhanced replacement of O 2− by N 3− . In all three systems, this anionic substitution resulted in a reduction of the optical band gap by approximately 1 eV (Ti) and up to 2.1 eV (Zr) compared to the respective oxides. For Mg 0.25 Ca 0.65 Y 0.1 Ti(O,N) 3 an optical band gap of 2.2 eV was observed, appropriate for a solar water splitting photocatalyst. The Zr-based oxynitrides required a by a factor of 2 higher nitrogen contents to significantly reduce the optical band gap and the measured values of 2.9 eV–3.2 eV are larger compared to the Ti-based oxynitride. Bulk thermal stability was revealed up to T = 881 K. In general, the thermal stability decreased with increasing substitution levels due to an increasing deviation from the ideal anionic composition as demonstrated by O/N analysis. [ABSTRACT FROM AUTHOR]

Abstract: Most cases of Alzheimer''s disease (AD) arise through interactions between genetic and environmental factors. It is believed that hypoxia is an important environmental factor influencing the development of AD. Our group has previously demonstrated that hypoxia increased β-amyloid (Aβ) generation in aged AD mice. Here, we further investigate the pathological role of prenatal hypoxia in AD. We exposed the pregnant APPSwe/PS1A246E transgenic mice to high-altitude hypoxia in a hypobaric chamber during days 7–20 of gestation. We found that prenatal hypoxic mice exhibited a remarkable deficit in spatial learning and memory and a significant decrease in synapses. We also documented a significantly higher level of amyloid precursor protein, lower level of the Aβ-degrading enzyme neprilysin, and increased Aβ accumulation in the brain of prenatal hypoxic mice. Finally, we demonstrated striking neuropathologic changes in prenatal hypoxic AD mice, showing increased phosphorylation of tau, decreased hypoxia-induced factor, and enhanced activation of astrocytes and microglia. These data suggest that although the characteristic features of AD appear later in life, hypoxemia in the prenatal stage may contribute to the pathogenesis of the disease, supporting the notion that environmental factors can trigger or aggravate AD. [Copyright &y& Elsevier]

Abstract: The nuclear receptor related 1 (Nurr1) transcription factor contributes to the development and maintenance of dopamine (DA) neurons in the brain. We found that heterozygous Nurr1 knockout (Nurr1 +/−) influenced the age-dependent decline in the number of DA neurons and influenced DA signaling. We examined the DA marker, tyrosine hydroxylase, using immunohistochemistry, and we measured DA signaling using fast-scan cyclic voltammetry in 3 age groups of wild-type (Nurr1 +/+) and mutant (Nurr1 +/−) mice: 3–6, 9–12, and 15–23 mo old. Prior to significant loss of DA neurons and to the onset of parkinsonian symptoms, young Nurr1 +/− mice (3–6 mo) exhibited a decrease in peak evoked DA release that was partially countered by a decrease in the rate of DA reuptake. As peak evoked DA release declined with age for both the wild-type and Nurr1 +/− mice, both genotypes manifested decreased DA reuptake. As the DA release fell further with age, decreased DA reuptake eventually could not adequately compensate the Nurr1 +/− mice. The results indicated that Nurr1 deficiency led to impaired DA release even before significant DA neuron loss. [Copyright &y& Elsevier]

Abstract: β-Zn4Sb3 compounds doped with minute amounts of Cd were synthesized by the MS-SPS technique, which involves melt spinning (MS) followed by spark plasma sintering (SPS), and the microstructures, thermoelectric and thermodynamic properties were systematically characterized. The non-equilibrium MS-SPS technique generates multi-scale nanostructures in the MS-prepared ribbon-shape samples and the resulting compacted bulk materials. These unique multiple nanostructures result in substantial reductions in lattice thermal conductivities, particularly for samples with a large number of ZnSb nanodots with sizes of 10–30nm. Meanwhile, Cd-doping remarkably improves the electrical properties of the (Zn1− x Cd x )4Sb3 compounds by a slight decrease in electrical conductivity and an apparent enhancement of the Seebeck coefficient. Therefore, the dimensionless figure of merits are significantly improved and the maximum value reaches ∼1.30 for the (Zn0.99Cd0.01)4Sb3 sample at 700K, representing ∼13% and ∼23% improvements compared with the undoped MS-SPS sample and the 1% Cd-doped melting ingot, respectively. In particular, this value shows no degradation after 10 heat cycles from 300 to 700K or 30h annealing at 680K in vacuum, whereas the ZT of neat sample decreases by ∼20% to a relatively low value of ∼1.0 after 30h annealing. The enhanced thermal stability of ZT along with the suppressing effect on the low-temperature α–β phase transition clearly indicates a large improvement in thermodynamic stability as a result of minute Cd-doping. All the above-mentioned benefits make the minute Cd-doped β-Zn4Sb3 compound prepared by the MS-SPS technique a promising candidate for mid-range temperature thermoelectric power generation applications. [Copyright &y& Elsevier]

Abstract: The Eu2+-doped Ba3Si6O12N2 green phosphor (Eu x Ba3−x Si6O12N2) was synthesized by a conventional solid state reaction method. It could be efficiently excited by UV-blue light (250–470nm) and shows a single intense broadband emission (480–580nm). The phosphor has a concentration quenching effect at x=0.20 and a systematic red-shift in emission wavelength with increasing Eu2+ concentration. High quantum efficiency and suitable excitation range make it match well with the emission of near-UV LEDs or blue LEDs. First-principles calculations indicate that Ba3Si6O12N2:Eu2+ phosphor exhibits a direct band gap, and low band energy dispersion, leading to a high luminescence intensity. The origin of the experimental absorption peaks is clearly identified based on the analysis of the density of states (DOS) and absorption spectra. The photoluminescence properties are related to the transition between 4f levels of Eu and 5d levels of both Eu and Ba atoms. The 5d energy level of Ba plays an important role in the photoluminescence of Ba3Si6O12N2:Eu2+ phosphor. The high quantum efficiency and long-wavelength excitation are mainly attributed to the existence of Ba atoms. Our results give a new explanation of photoluminescence properties and could direct future designation of novel phosphors for white light LED. [Copyright &y& Elsevier]

Abstract: PITX3 is a transcription factor important for the differentiation and survival of midbrain dopaminergic neurons during the development. Recent reports suggest that single nucleotide polymorphisms (SNP) in the gene may be associated with Parkinson''s disease (PD). To verify their findings and to determine the nature of the association in a subset of our PD patients we have analyzed two PITX3 SNPs (rs2281983 and rs4919621) in 265 PD patients and compared them with 210 age-matched healthy controls. Our data show that the substitutions of C/T in SNP1 and A/T in SNP2 are significantly higher in PD, and this finding is even more robust in young onset and familial PD as compared with age-matched healthy controls. Our findings indicate that PITX3 may play a role in the pathogenesis of PD. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the clinical and biological effects of chronic pramipexole (PPX) therapy in a proposed animal model of restless legs syndrome (RLS). Methods: We developed an animal model of RLS with iron deprivation (ID) plus bilateral 6-hydroxydopamine (6-OHDA) lesions in the A11 nuclei in C57BL/6 mice, which showed increased locomotor activities that lessened by application of the dopamine agonist PPX. The mice were treated with PPX for a period of 28 (short-term observation) and 84days (long-term observation). We measured the behavioral performances, iron levels, monoamine contents, and dopamine receptor bindings in the spinal cord after treatment. Results: C57BL/6 mice with ID diet plus 6-OHDA lesions in A11 nuclei showed significantly increased movement (Moving Time increased by 186% and total travel distance increased by 162%). Acute and chronic treatment with three doses of PPX (0.1mg/kg, 0.5mg/kg, and 2.5mg/kg) attenuated locomotor activities in the mice. Biochemical assays demonstrated that the ID+6-OHDA mice had significant lower levels of dopamine and HVA, and D2 receptor density in the lumbar cord. Chronic treatment with PPX did not significantly alter dopamine or serotonin metabolites in the lumbar cord. There was a trend to mildly decreased D3, but not D1 or D2 receptor density. PPX treatment also caused a modestly increased D1, but not D2 or D3, receptor affinity. The reduction in spinal cord iron seen in the ID+6-OHDA mice was partially attenuated by long-term PPX treatment compared to untreated animals. Conclusions: Pramipexole produced long-term improvement of the RLS-like symptoms in our proposed animal model, caused a partial recovery of spinal iron deficiency, and modestly increased D1 receptor affinity. [Copyright &y& Elsevier]

Abstract: NURR1 is a transcription factor essential for the development, survival, and functional maintenance of midbrain dopaminergic (DAergic) neurons and NURR1 is a potential susceptibility gene for Parkinson''s disease (PD). To determine whether NURR1 gene expression is altered in patients with PD, we measured its expression in human peripheral blood lymphocytes (PBL) in 278 patients with PD, 166 healthy controls (HC), and 256 neurological disease controls (NDC) by quantitative real-time PCR. NURR1 gene expression was significantly decreased in patients with PD (particularly those with family history of PD) as compared with HC (p <0.01) and also as compared with NDC (p <0.05). There was no significant difference in NURR1 gene expression among PD patients with or without anti-PD medications. When adjusted for gender, age, and ethnicity, lower levels of NURR1 gene expression were associated with significantly increased risk for PD in women, in patients 60 years old or older, and in patients of Caucasian origin. The observed reduction in PBL NURR1 gene expression indicates possible systemic involvement in PD, and the finding may help identify individuals with PD and other disorders associated with impaired central DAergic system. [Copyright &y& Elsevier]

Abstract: Parkinson''s disease (PD) has been proposed to result from a combination of genetic susceptibility and environmental exposure. Dysfunction of the ubiquitin–proteasome system (UPS) has been implicated in neuron degeneration and in pathogenesis of PD. Nurr1, a member of nuclear receptor superfamily, is a potential susceptibility gene for PD. In this in vitro and in vivo study, we investigated whether Nurr1 deficiency may predispose to environmental proteasome inhibitors-induced neuron injury. We found that lactacystin, an irreversible proteasome inhibitor, caused greater injury to SH-SY5Y cells that Nurr1 expression has been suppressed by small interference RNA (siRNA). On the contrary, the Nurr1 overexpressed SH-SY5Y cells by Nurr1 expression vector transfection rescued the lactacystin-induced injury. In vivo, stereotactic microinjection with lactacystin into right median forebrain bundle (MFB) of mice caused significant inhibition of the proteasome activity in both Nurr1 knock out heterozygous (Nurr1 +/−) mice and their littermate wild-type (Nurr1 +/+) mice. At same time, we found that there was a severer loss of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) and greater reduction of striatal dopamine (DA) levels in Nurr1 +/− mice as compared with that in Nurr1 +/+ mice. Furthermore, lactacystin-induced increase of cleaved PARP, cleaved caspase3 and p53 and decrease of bcl-2 in SN was significantly enhanced in Nurr1 +/− mice. These findings suggest that reduction in Nurr1 expression increases susceptibility to DAergic neuron injury induced by UPS impairment. [Copyright &y& Elsevier]

Abstract: Mutations in the parkin gene and the PTEN-induced putative kinase 1 gene (PINK1) have been identified as the most common causes of autosomal recessive early-onset Parkinson disease (EOPD). To investigate the presence of the parkin and PINK1 gene mutation(s) and to explore genotype–phenotype correlations in American Caucasian families with EOPD from North American, we screened these two genes in probands of six families by direct sequencing, semi-quantitative PCR and RT-PCR. No PINK1 gene mutation was found in any of the probands, but compound heterozygous mutations (EX 3 del and EX 3_4 del) in the parkin gene were identified in one family. Extended analysis of the parkin-positive family showed the phenotype of patients was that of classic autosomal recessive EOPD, characterized by early age at onset, slow progression, beneficial response to levodopa, and levodopa-related motor complications. Three heterozygous mutation carriers (EX 3 del or EX 3_4 del) were free of any neurological symptoms. None of 62 healthy controls harbored EX 3 del or EX 3_4 del mutation. Our data suggest that compound heterozygous mutations (EX 3 and EX 3_4 del) in the parkin gene were the cause of EOPD in one of six Caucasian families; heterozygous EX 3 del and heterozygous EX 3_4 del forms were insufficient to cause this disorder, consistent with a loss-of-function mechanism of the parkin mutations. The results may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling. [Copyright &y& Elsevier]

Abstract: Parkinson''s disease (PD) is the second most common neurodegenerative disease with major clinical features of bradykinesia, rigidity, resting tremor, and postural instability. Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been identified both in familial and sporadic cases of PD. Recently, a P755L variant in the LRRK2 gene has been found to be responsible for 2% of Chinese patients with sporadic PD. To evaluate the frequency of the LRRK2 P755L variant in North American Caucasian patients with PD, we screened 426 PD patients and 37 additional patients with the combination of PD and essential tremor (ET) from our Parkinson Disease Center and Movement Clinic at Baylor College of Medicine. No P755L variant was found in our PD cohort. Therefore, we conclude that LRKK2 P755L variant is a rare cause of Caucasian PD and has no diagnostic utility in genetic testing of this population of patients. [Copyright &y& Elsevier]

Abstract: In addition to the G2019S mutation in the leucine-rich repeat kinase 2 gene (LRRK2), which is particularly frequent in patients of Ashkenazi Jewish and Northern African origin, three amino acid substitutions (R1441C, R1441G, and R1441H), all at the same residue (R1441), have been identified as important genetic causes of Parkinson disease (PD). To evaluate the frequency of R1441C/G/H and G2019S mutations in the LRRK2 gene in North American patients with PD and to explore genotype–phenotype correlations, we screened 496 PD patients from North America. One Hispanic female was heterozygous for the LRRK2 R1441G mutation, and six other cases including 2 non-Jewish/non-Hispanic whites, 3 Ashkenazi Jewish, and 1 Hispanic, were found to be heterozygous for the LRRK2 G2019S mutation. G2019S mutation in the LRRK2 gene is a common mutation associated with PD in a North American population, especially in Jewish PD patients (10.7%), while the R1441C/G/H mutation occurs at a relatively low frequency in North Americans except possibly in Hispanics for R1441G. All six G2019S carriers shared a common haplotype with that observed in Europeans and North Africans. The clinical features of all seven cases with LRRK2 mutation were quite broad and included early and late disease onset. These finding may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling. [Copyright &y& Elsevier]

Abstract: Several mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been identified both in familial and sporadic cases of Parkinson''s disease (PD). G2019S, located at a kinase (MAPKKK) domain, is the most common mutation in the LRRK2 gene in PD, Two adjacent mutations (I2012T and I2020T) were mapped to the same domain suggesting shared pathogenic mechanism of these mutations. Since phenotypes of PD overlap with essential tremor (ET), we investigated LRRK2 G2019S, I2012T, and I2020T mutations in a cohort of 272 patients with ET. No mutations were found in our ET cohort and, therefore, we conclude that LRKK2 I2012T, G2019S and I2020T variants are rare causes of Caucasian ET. [Copyright &y& Elsevier]