Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

基于改进Converse断裂点模型和加权Voronoi图的区域城镇体系结构研究——以天水市为例

在对Converse断裂点模型进行改进的基础上,通过构建评价指标体系和计算城镇中心性强度,对天水市城镇体系等级结构进行了划分;通过运用加权Voronoi图,划分了城镇影响范围和城镇经济区。研究表明:1)天水市城镇体系等级分化非常明显,可按中心性值的大小分为3个等级,其中一级城镇主要为天水各县区政府所在地;2)基于加权Voronoi图的城镇经济区打破了行政区划界线,更符合区域"城镇-腹地"相互联系和作用的实际;3)城镇影响空间既受城镇综合实力和区位交通条件的影响,也与地形、资源分布以及历史文化等因素密切相关。在天水市东部和南部,城镇空间影响范围明显大于中部和北部地区。

应用Converse3D设计和实现虚拟校园

高等院校合理运用虚拟校园系统,不仅立体展示校园实景信息和校园文化,而且可以更有效地进行学校的组织管理,同时能够提高学校的知名度、增强学校的竞争力。本文以安庆职业技术学院校园为基础,建立三维实景模型,利用Converse3D虚拟漫游平台,建立虚拟校园系统,实现实时交互式漫游。

Controlling and synchronizing spatiotemporal chaos of the coupled Bragg acousto-optical bistable map system using nonlinear feedback

In this paper we present the control and synchronization of a coupled Bragg acousto-optic bistable map system using nonlinear feedback technology. This nonlinear feedback technology is useful to control a temporally chaotic system as well as a spatiotemporally chaotic system. It can be extended to synchronize the spatiotemporal chaos. It can work in a wide range of the controlled and synchronized signals, so it can decrease the sensitivity down to a noise level. The synchronization can be obtained by the analysis of the largest conditional Lyapunov exponent spectrum, and easily implemented in practical systems just by adjusting the coupled strength without any pre-knowledge of the dynamic system required.

Strong Converse Inequalities for Certain Mixed Szász-Beta Operators

In this paper,a strong converse inequality of type B in terms of a new Kfunctional Kλα f,t2(0 < α < 2,0 ≤λ≤ 1) for certain mixed Szász-Beta operators is given.By this inequality,the converse theorem can be obtained for the operators.

Strong Converse Inequalities for Szasz-Mirakjan Operators with Weights

In this paper, we give the strong converse inequalities of type B with the new K-functional Kλα(f,t2)w(0 ≤λ≤ 1, 0 < α < 2) on weighted approximation for Sz′asz-Mirakjan operators, which extend the previous results.

Acousto-Optically Q-Switched Operation of Yb:CNGG Disordered Crystal Laser

We report the repetitively Q-switched laser operation of the Yb-doped calcium niobium gallium garnet disordered garnet crystal, achieved with an acousto-optic modulator in a compact plano-concave resonator that is endpumped by a 935-nm diode laser. An average output power of 1.96 W is produced at pulse repetition rate of50 k Hz at emission wavelengths around 1035 nm, with a slope efficiency of 16%. The highest pulse energy of 269 μJ is generated at pulse repetition rate of 1 k Hz, with pulse width 12.1 ns and peak power 20.53 kW.

Chloromycetin resistance of clinically isolated E coli is conversed by using EGS technique to repress the Chloromycetin acetyl transferase

AIM： To explore the possibility of repression of chloromycetin （Cm） acyl transferase by using external guided sequence （EGS） in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS： EGS directed against chloromycetin acetyl transferase gene （cat） was cloned to vector pEGFP-C1 which contains the kanamycin （Kin） resistance gene. The recombinant plasmid pEGFP-C1＋EGScatl＋cat2 was constructed and the blank vector without EGS fragment was used as control plasmids. By using the CaCl2 transformation method, the recombinant plasmids were introduced into the clinically isolated Cm resistant but Km sensitive E coli strains. Transformants were screened on LB agar plates containing Kin. Extraction of plasmids and PCR were applied to identify the positive clones. The growth curve of EGS transformed bacteria cultured in broth with Cm resistance was determined by using spectrophotometer at A600. Drug sensitivity was tested in solid culture containing Cm by using KB method. RESULTS： Transformation studies were carried out on 16 clinically isolated Cm-resistant （250 μg/mL of Cm） E colistrains by using pEGFP-C1-EGScatlcat2 recombinant plasmid. Transformants were screened on LB-agar plates containing Km after the transformation using EGS. Of the 16 tested strains, 4 strains were transformed successfully. Transformants with EGS plasmid showed growth inhibition when grown in liquid broth culture containing 200 μg/mL of Cm. In drug sensitivity test, these strains were sensitive to Cm on LB-agar plates containing 200 μg/mL of Cm. Extraction of plasmids and PCR amplification showed the existence of EGS plasmids in these four transformed strains. These results indicated that the Cat of the four clinical isolates had been suppressed and the four strains were converted to Cm sensitive ones. CONCLUSION： The EGS directed against Cat is able to inhibit the expression of Cat, and hence convert Cm- resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of converting the phenotype of clinical drug-resistant isolates strains to drug-sensitive ones.

STRONG CONVERSE INEQUALITY FOR SZASZ-DURRMEYER OPERATORS

For Szasz-Durrmeyer operators L.(f,x),1<p ∞ we prove that, forsome m,where(x)2=x,M>0,is Ditzian-Totik modulus of smoothness.

High-Resolution Broadband Millimeter-Wave Astrophysical Spectrometer with Triple Product Acousto-Optical Processor

An advanced conceptual design of a high-bit-rate triple product acousto-optical processor is presented that can be applied in a number of astrophysical problems. We briefly describe the Large Millimeter Telescope as one of the potential observational infrastructures where the acousto-optical spectrometer can be successfully used. A summary on the study of molecular gas in relatively old (age > 10 Myr) disks around main sequence stars is provided. We have identified this as one of the science cases in which the proposed processor can have a big impact. Then we put forward triple product acousto-optical processor is able to realize algorithm of the space-and-time integrating, which is desirable for a wideband spectrum analysis of radio-wave signals with an improved resolution providing the resolution power of about 105 - 106. It includes 1D-acousto-optic cells as the input devices for a 2D-optical data processing. The importance of this algorithm is based on exploiting the chirp Z-transform technique providing a 2D-Fourier transform of the input signals. The system produces the folded spectrum, accumulating advantages of both space and time integrating. Its frequency bandwidth is practically equal to the bandwidth of transducers inherent in acousto-optical cells. Then, similar processor is able to provide really high frequency resolution, which is practically equal to the reciprocal of the CCD-matrix photo-detector integration time. Here, the current state of developing the triple product acousto-optical processor in frames of the astrophysical instrumentation is shortly discussed.

Enabling heterogeneous catalysis to achieve carbon neutrality: Directional catalytic conversion of CO_(2) into carboxylic acids

The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.

High-Power Continuous-Wave and Acousto-Optical Q-Switched Ho:(Sc_(0.5)Y_(0.5))_2SiO_5 Laser Pumped by Laser Diode

We experimentally investigate the continuous-wave(cw)and acousto-optical(AO)Q-switched performance of a diode-pumped Ho:(Sc_(0.5)Y_(0.5))_2SiO_5(Ho:SYSO)laser.A fiber-coupled laser diode at 1.91m is employed as the pump source.The cw Ho:SYSO laser produces 13.0 W output power at 2097.9 nm and 56.0%slope efficiency with respect to the absorbed pump power.In the AO Q-switched regime,at a pulse repetition frequency of 5 kHz,the Ho:SYSO laser yields 2.1 mJ pulse energy and 21 ns pulse width,resulting in a calculated peak power of 100 k W.In addition,at the maximum output level,the beam quality factor of the Q-switched Ho:SYSO laser is measured to be about 1.6.

The Application of Lights-Conversed Polyethylene Film for Agriculture

Lanthanum-rhodamine (6G and B) complexes were synthesized by Rheological Phase Reaction Method. Lanthanum-rhodamine (6G and B) complexes doped polyethylene films which have a function of lights-conversion were prepared. The emission and excitation spectra were measured. The experiments of growing seedling and culture were carried out in the shed built with doped and undoped polyethylene films. Lanthanum-rhodamine doped polyethylene films which have a function of lights-conversion can efficiently convert the green light in the sunlight to the red light for photosynthesis of crops, to promote the maturing of crops and raise the yield of crops.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

High-power xenon lamp-pumped Er:YAP pulse laser operated in free-running and acousto-optical Q-switching modes

We demonstrate a high-energy and high-power pulse laser on a xenon lamp-pumped Er:YAP crystal. The laser performance and thermal focal lengths under different working frequencies are discussed. The results show that the thermal lens effect is gradually aggravated with the increase of working frequencies, and even working at 100 Hz, a single pulse energy of 234 m J can be achieved. A maximum average power of 41.5 W is achieved with a working frequency of 20 Hz and slope efficiency of 2.82%. This output power is much higher than other xenon lamp-pumped erbium laser devices.A Q-switched laser is demonstrated by using the TeO2crystal, the maximum output energies of 11.5 m J and 3.5 m J are obtained at 50 and 100 Hz, the corresponding peak powers are 93.4 k W and 17.2 kW, respectively.The laser wavelengths and beam quality factors are also characterized in the free-running and Q-switched modes. A higher pulse energy and peak power laser could be achieved further by improving the damage threshold of TeO2acousto-optical Q-switching. All the experimental results illustrate that the xenon lamp-pumped Er:YAP laser is a promising candidate for high-power and high-frequency mid-infrared laser devices.

Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex

Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.

Dealuminated Hβ zeolite for selective conversion of fructose to furfural and formic acid

The fructose-to-furfural transformation is facing major challenges in the selectivity and high efficiency. Herein, we have developed a simple and effective approach for the selective conversion of fructose to furfural using Hβ zeolite modified by organic acids for dealuminization to regulate its textural and acidic properties. It was found that citric acid-dealuminized Hβ zeolite possessed high specific surface areas, wide channels and high Brønsted acid amount, which facilitated the selective conversion of fructose to furfural with a maximum yield of 76.2% at433 K for 1 h in the γ-butyrolactone(GBL)-H_(2)O system, as well as the concomitant formation of 83.0% formic acid. The^(13)C-isotope labelling experiments and the mechanism revealed that the selective cleavage of C1–C2 or C5–C6 bond on fructose was firstly occurred to form pentose or C5 intermediate by weak Brønsted acid, which was then dehydrated to furfural by strong Brønsted acid. Also this dealuminized Hβ catalyst showed the great recycling performance and was active for the conversion of glucose and mannose.

Oxygen functionalization-assisted anionic exchange toward unique construction of flower-like transition metal chalcogenide embedded carbon fabric for ultra-long life flexible energy storage and conversion

The metal-organic framework(MOF)derived Ni–Co–C–N composite alloys(NiCCZ)were“embedded”inside the carbon cloth(CC)strands as opposed to the popular idea of growing them upward to realize ultrastable energy storage and conversion application.The NiCCZ was then oxygen functionalized,facilitating the next step of stoichiometric sulfur anion diffusion during hydrothermal sulfurization,generating a flower-like metal hydroxysulfide structure(NiCCZOS)with strong partial implantation inside CC.Thus obtained NiCCZOS shows an excellent capacity when tested as a supercapacitor electrode in a three-electrode configuration.Moreover,when paired with the biomass-derived nitrogen-rich activated carbon,the asymmetric supercapacitor device shows almost 100%capacity retention even after 45,000 charge–discharge cycles with remarkable energy density(59.4 Wh kg^(-1)/263.8μWh cm^(–2))owing to a uniquely designed cathode.Furthermore,the same electrode performed as an excellent bifunctional water-splitting electrocatalyst with an overpotential of 271 mV for oxygen evolution reaction(OER)and 168.4 mV for hydrogen evolution reaction(HER)at 10 mA cm−2 current density along with 30 h of unhinged chronopotentiometric stability performance for both HER and OER.Hence,a unique metal chalcogenide composite electrode/substrate configuration has been proposed as a highly stable electrode material for flexible energy storage and conversion applications.

Enhancing I^(0)/I^(-)Conversion Efficiency by Starch Confinement in Zinc-lodine Battery

The redox couple of I^(0)/I^(-)in aqueous rechargeable iodine–zinc(I^(2)-Zn)batteries is a promising energy storage resource since it is safe and cost-effective,and provides steady output voltage.However,the cycle life and efficiency of these batteries remain unsatisfactory due to the uncontrolled shuttling of polyiodide(I_(3)^(-)and I_(5)^(-))and side reactions on the Zn anode.Starch is a very low-cost and widely sourced food used daily around the world.“Starch turns blue when it encounters iodine”is a classic chemical reaction,which results from the unique structure of the helix starch molecule–iodine complex.Inspired by this,we employ starch to confine the shuttling of polyiodide,and thus,the I^(0)/I^(-)conversion efficiency of an I^(2)-Zn battery is clearly enhanced.According to the detailed characterizations and theoretical DFT calculation results,the enhancement of I^(0)/I^(-)conversion efficiency is mainly originated from the strong bonding between the charged products of I_(3)^(-)and I_(5)^(-)and the rich hydroxyl groups in starch.This work provides inspiration for the rational design of high-performance and low-cost I^(2)-Zn in AZIBs.