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Abstract Background Currently, the synthesis of compounds based on microbial cell factories is rapidly advancing, yet it encounters several challenges. During the production process, engineered strains frequently encounter disturbances in the cultivation environment or the impact of their metabolites, such as high temperature, acid-base imbalances, hypertonicity, organic solvents, toxic byproducts, and mechanical damage. These stress factors can constrain the efficiency of microbial fermentation, resulting in slow cell growth, decreased production, significantly increased energy consumption, and other issues that severely limit the application of microbial cell factories. Results This study demonstrated that sterol engineering in Kluyveromyces marxianus, achieved by overexpressing or deleting the coding genes for the last five steps of ergosterol synthase (Erg2-Erg6), altered the composition and ratio of sterols in its cell membrane, and affected its multiple tolerance. The results suggest that the knockout of the Erg5 can enhance the thermotolerance of K. marxianus, while the overexpression of the Erg4 can improve its acid tolerance. Additionally, engineering strain overexpressed Erg6 improved its tolerance to elevated temperature, hypertonic, and acid. YZB453, obtained by overexpressing Erg6 in an engineering strain with high efficiency in synthesizing xylitol, produced 101.22 g/L xylitol at 45oC and 75.11 g/L xylitol at 46oC. Using corncob hydrolysate for simultaneous saccharification and fermentation (SSF) at 46oC that xylose released from corncob hydrolysate by saccharification with hemicellulase, YZB453 can produce 45.98 g/L of xylitol, saving 53.72% of the cost of hemicellulase compared to 42oC. Conclusions This study elucidates the mechanism by which K. marxianus acquires resistance to various antifungal drugs, high temperatures, high osmolarity, acidity, and other stressors, through alterations in the composition and ratio of membrane sterols. By employing sterol engineering, the fermentation temperature of this unconventional thermotolerant K. marxianus was further elevated, ultimately providing an efficient platform for synthesizing high-value-added xylitol from biomass via the SSF process at temperatures exceeding 45 °C.

A 100-MeV Compact Electron Accelerator design has been proposed for Very High Energy Electron (VHEE) radiotherapy research at Tsinghua University. The microwave source for this system is a 50 MW X-band klystron, paired with a pulse compressor featuring a correction cavity chain. During high-power test, the system achieved a flat-top power gain three times the input. The acceleration system consists of three main components: a backward traveling-wave buncher that bunches and accelerates electrons from a thermionic cathode gun to 8 MeV, followed by two 72-cell X-band constant-gradient traveling-wave accelerating structures, which further increase the electron energy to 100 MeV with a gradient of 80 MV/m. The total length of the system is 1.8 m, and its design is detailed in this paper.

Abstract Over the past three decades, studies have indicated a mobile surface layer with steep gradients on glass surfaces. Among various glasses, polymers are unique because intramolecular interactions — combined with chain connectivity — can alter surface dynamics, but their fundamental role has remained elusive. By devising polymer surfaces occupied by chain loops of various penetration depths, combined with surface dissipation experiments and Monte Carlo simulations, we demonstrate that the intramolecular dynamic coupling along surface chains causes the sluggish bulk polymers to suppress the fast surface dynamics. Such effect leads to that accelerated segmental relaxation on polymer glass surfaces markedly slows when the surface polymers extend chain loops deeper into the film interior. The surface mobility suppression due to the intramolecular coupling reduces the magnitude of the reduction in glass transition temperature commonly observed in thin films, enabling new opportunities for tailoring polymer properties at interfaces and under confinement and producing glasses with enhanced thermal stability.

Traditional impact-resistance materials relying on the combination of supporting materials and energy-dissipation elastomers can effectively reduce shock load, yet the sharp interface between two types of materials causes discontinuous stress transfer and cracking. Here, inspired by the squid beak, we report a type of high impact-resistance gradient elastomers with large-scale modulus gradient with about three orders of magnitude (modulus range of 7 × 103 ∼ 7 × 106 Pa) and high energy dissipation (loss factor > 0.6) over a wide temperature range by diffusively introducing stiff polymers in a highly damping elastomer with controlled mechanical properties. Under the action of an external force, our gradient elastomers exhibit soft-while-stiff attributes, combining cushioning and support. In drop hammer impact tests, our gradient materials can reduce impact strength by 80 %, significantly better than commercial protective gear. It is worth mentioning that the modulus of the bottom layer matches that of the tissues for better protection.

A light source project named very compact inverse Compton scattering gamma-ray source (VIGAS) is under development at Tsinghua University. VIGAS aims to generate monochromatic high-energy gamma rays by colliding 350-MeV electron beams with 400-nm laser photons within a 12-m beamline. To produce a high-energy electron beam in such a compact space, the system consists of an S-band high-brightness injector and six X-band high-gradient accelerating structures. The goal of the X-band structure is to operate at a high gradient of 80 MV/m. Therefore, we adopts the constant gradient traveling wave approach, where the iris from the first cell to the end cell is tapered. The structure has 72 cells, including 70 cells and 2 couplers, so we named it XT72. The frequency of XT72 is selected to 11.424 GHz, and the 2π/3 mode is adopted. In this paper, we present a comprehensive study covering the detailed design, fabrication, rf tuning, and high-power test results of the first XT72. Additionally, we compare the performance of this structure to that of the previous constant impedance structure. Our results demonstrate that the XT72 is capable of operating at an 80-MV/m gradient with a lower breakdown rate. This advancement paves the way for the development of VIGAS project and contributes to the wider application of X-band room-temperature high-gradient structures in compact accelerator facilities.

Over the past few decades, conjugate heat transfer (CHT) technology has been instrumental in predicting temperature fields within aerospace engines, guiding engine design with its predictive capabilities. This paper comprehensively surveys the foundational technologies of CHT and their applications in engine design, backed by an extensive literature review. A novel coupling iteration methodology, su-F-TFTB, was proposed. Following this, it introduced grid splicing technology tailored for heat flux conservation, which significantly enhances the adaptability of CHT grids. Ultimately, this study employed the self-developed Aerospace Engine Numerical Simulation (AENS v4.0.1) software to perform CHT analyses on NASA-C3X turbine blades equipped with ten radial cooling systems. A comparative analysis of pressure distributions across various density meshes was undertaken to affirm mesh independence. Furthermore, the impacts of the Spalart–Allmaras (SA) one-equation model and k–ω Shear Stress Transport (SST) two-equation model on the temperature distribution in conjugate heat transfer were investigated. The results indicated that the k–ω SST model exhibited superior performance, aligning closely with NASA experimental data. This validation confirmed the effectiveness of the software.

Remote ischemic perconditioning (RIPerC) could improve neuronal damage and inhibit inflammation and apoptosis. We conducted an in-depth exploration of the protective mechanism of RIPerC in cerebral ischaemia injury. In this study, a middle cerebral artery occlusion (MCAO) mouse model was built. According to whether to undergo RIPerC treatment and the duration of cerebral infarction, mice were divided into 5 groups: Sham group, MCAO 3.0 h group, MCAO 4.5 h group, MCAO 3.0 h + RIPerC group, and MCAO 4.5 h + RIPerC group. Overexpressed or silenced miR-153-5p was transfected into the cells to analyse the effects of oxygen-glucose deprivation (OGD) treatment on Neuro-2a cell viability, apoptosis, and related gene expressions by performing quantitative real-time polymerase chain reaction (qRT-PCR), MTT assay, flow cytometry, and Western blot. Bioinformatics analysis, qRT-PCR, dual-luciferase experiment, and RNA immunoprecipitation (RIP) were used to screen and verify the miRNA and downstream mRNA-targeted Toll-like receptor 4 (TLR4). The rescue test further verified the effects of the above target genes and miR-153-5p on the apoptosis of OGD-injured cells, apoptosis-related proteins, and the p65/IkBa pathway. The plasma levels of miR-153-5p in 68 patients with ischaemic stroke were detected within 6 hours of onset, and the patients were followed up for 3 months. We found that, in in vivo studies, RIPerC treatment inhibits cerebral infarction volume and neurological damage, and promotes the expression of miR-153-5p in the MCAO animal model. The expression of miR-153-5p in OGD cells was inhibited, and its upregulation protected Neuro-2a cells. TLR4 was predicted to be the target gene of miR-153-5p and could offset the effect of miR-153-5p mimic on OGD cell protection after up-regulating TLR4. TLR4 overexpression promoted the activation of OGD on the p65/IkBa pathway. Compared with the high plasma miR-153-5p group, the 3-month overall survival rate of patients with ischaemic stroke in the low plasma miR-153-5p group was significantly lower (c2 = 5.095, p = 0.024). In conclusion, RIPerC intervention inhibits the damage caused by cerebral ischaemia partially through the miR-153-5p/TLR4/p65/IkBa signalling pathway.

Abstract Background Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients. Method The PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I2 index were analyzed. Stata 15 was used for statistical analysis. Results A total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27–2.37, I2 = 0.0%, n = 410; frozen RR: 1.44, 95% CI: 1.14–1.81, I2 = 0.0.%, n = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33–2.23, I2 = 0.0%, n = 497; intrauterine RR: 1.39, 95% CI: 1.09–1.78, I2 = 0.0%, n = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28–2.68; I2 = 20.1%, n = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25–5.21: I2 = 63.2%, n = 472) and live birth rate (RR: 1.43, 95% CI: 0.86–2.36; I2 = 52.5%; n = 372) when a random-effects model was employed. Conclusion The administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.

Introduction Therapies targeting histone deacetylase (HDAC) have gained wider attention in the treatment of various clinical conditions. However, the use of HDAC inhibitors in pre-clinical trials in the case of Parkinson’s disease (PD) is very limited. In the present study, the HDAC inhibitor, entinostat, was tested in animals induced with Parkinson’s disease experimentally. Material and methods Wistar male rats (150 ±10 g) were administered with rotenone (2 mg/kg/day, s.c.) for 21 days to induce PD, while entinostat (20 mg/kg) was given intraperitoneally. Then, the neurological functions, PD markers, and HDACs were analysed in the control and experimental animals. Results The results demonstrated that rats that received entinostat displayed progressive motor, behavioural, and neurological function with attenuated α-synuclein and improved tyrosine-hydroxylase compared to control cells. Moreover, the induction of PD in rats demonstrated reduced levels of H2S, dopamine, 3, and 4-dihydroxyphenylacetic acid (DOPAC), and increased monoamine oxidase activity in PD rats. However, the rats that received entinostat demonstrated progressive levels of dopa and DOPAC, with attenuated levels of HDAC-2, -4, and -6 mRNA in the PD rats compared to controls. On the other hand, elevated (p < 0.01) levels of PD marker genes such as GDF3 and NMDA2b were reduced, with a significant increase in neuroprotective genes such as VDAC3 and CBX5 in entinostat-supplemented rats. Conclusions The study results suggest that inhibition of HDAC systematically improves the neurological functions, and hence treatments, emphasizing that HDACI, as the speculated mechanism, will be a promising mode of treatment in PD.

In this paper, a low-loss 90°-bending design in femtosecond laser-induced double-line waveguides is theoretically proposed and experimentally demonstrated. The bending is realized based on the total internal reflection of a corner mirror (made by precise diamond blade dicing) located at the intersection of a pair of waveguides perpendicular to each other. The waveguide bending performance was birefringence free, with the insertion loss of each bending below 0.8 dB. This method provides great flexibility and has great potential for the design of integrated photonics based on femtosecond laser-inscribed crystalline materials.

A compact X-band two-stage rf pulse compression system has been successfully designed, fabricated, and tested at Tsinghua X-band high-power test stand. The pulse compression system consists of a correction cavity chain, a first-stage, and a second-stage storage cavity. The correction cavity chain adopts a new design whose transmission loss and length are reduced by half compared with the old one. A detuning device is applied to the second-stage storage cavity so that the system can work in one-stage or alternatively two-stage compression mode. In the one-stage compression mode, a 150-ns, 70-MW flattop output, with a standard deviation of 1.5% in amplitude and 1° in phase, was generated with a gain factor of 3. In the two-stage compression mode, a first two-stage pulse compression experiment with correction cavities in the X band was performed. A peak power of 320 MW was achieved with a gain factor of 9.7 and full-width at half-maximum pulse durations of 53 ns.

Shortening the pulse length of input power is a possible approach to raise the accelerating gradient limit of normal conducting structures. We present a novel design of a parallel-coupled structure that operates at ultrashort input power pulses. The principle of the design is to shorten the filling time of the whole structure by feeding the cells individually so that the duration of power transmission between cells can be saved. An X-band (11.994 GHz) parallel-coupled structure design with a 10 ns pulse length is presented in this work. Previous high-power tests of X-band structure prototypes show that a gradient of 120 MV/m could be achieved for a 200 ns pulse length. Based on the law requiring that E^{30}t^{5}=constant, this 10-ns-structure design should be able to reach a gradient of 200 MV/m. A detailed circuit model and real-time electromagnetic field simulation methods for designing the parallel-coupling structure are also presented and discussed in this paper.

The mechanical response characteristics of rocks under cyclic loading conditions are crucial factors for evaluating and analyzing the stability of rock mass during underground excavation. In this study, based on fractal theory and a series of tests using the MTS815.02 rock mechanics test system, the classification and fractal characteristics of limestone specimen fragments are investigated. The results show that limestone specimens subjected to cyclic loading can generate more small-sized fragments than conventional compression, but the large-fragment-producing abilities of the two tests exhibit small difference. The mass fraction of the fragments in the cyclic loading test is obviously greater than that in the conventional test when the fragment size is less than 4.75 mm; however, only a small difference is observed between the cyclic loading tests with frequencies of 0.25 and 0.5 Hz. In the same type of test, a confining pressure is helpful in reducing the fragmentation of limestone specimen. As the size interval decreases, the shapes of limestone fragment transition from rectangular to long slice and then to square. The results also indicate that the confining pressure has a significant influence on the size-quantity and size-mass fractal dimensions of limestone fragments. The former has a positive correlation with the confining pressure, whereas the latter decreases with confining pressure. The conclusions obtained in this investigation can enrich the theoretical research on the failure response and mechanism of rock under cyclic loading conditions.

Due to inappropriate mining practices, water-conducting fracture zones can develop in an aquifer, not only destroying the surface-water environment but also causing water inrush, even hurting or killing workers. To avoid such disasters, investigating and simulating the evolution mechanism of water-conducting fractures are becoming a research focus in mining engineering, especially regarding the organisation and development of fractures. Our work mainly involved the design of low-strength analogous materials and the simulation of fracture evolution for weak-roof problems in shallow seam mining based on a self-built experimental hydromechanical coupling system. The experimental results show that the vertical stress in the roof increases first as the working face approaches and finally decreases to near its initial value as the working face passes. The relationship between fracture depth and coal-seam excavation distance is obviously nonlinear. The leakage velocity of surface water remains stable in the early stage of excavation and increases when the fracture develops through the main aquifuge. The maximum fracture depth is 76.18 m for the Yili coal mine with weak roofs and shallow coal seams. In addition, we numerically simulated and verified the evolution patterns with the FLAC3D platform. The simulated fracture depth of the Yili coal mine agreed with the in situ borehole observation very well and was more accurate than the output of the empirical formula. Our work provides new methods and relevant data for research on the evolution of water-conducting fractures in weak roofs during shallow seam mining.

This paper mainly involved the testing of self-designed hydrophilicity-related geomaterials and application of overlying strata monitoring in a mining area in Northwest China. We employed the orthogonal testing technique to select the ingredient ratio of hydrophilicity-related geomaterials and optimized the mechanical properties of materials, such as density, elastic modulus, Poisson ratio, compressive strength, tensile strength, and water absorption rate on the basis of regression analysis. It can be seen that the proportion of the mixture clearly determines the mechanical properties of similar materials. Among them, the content of silicone oil and the cement-Vaseline ratio have the most obvious effects on the mechanical properties of the material. By using the hydrophilicity-related geomaterials with ingredient optimization, we built a physical model to simulate the failure progress of the workface in one of the coal mines in Northwest China. It was shown that three remarkable characteristic parts, including collapse zone, fissure zone, and layer-separating space, appear in the overlying strata. Furthermore, the fractured zone above the separating band is just located under the main aquifer. Finally, compared with in-field data, it was verified that the height of the collapse zone and water-guiding fissure zone measured at three boreholes are in good agreement with the experiment. Thus, the failure mode of overburden and the vertical stress and displacement changes are consistent with the actual engineering. Self-developed hydrophilicity-related geomaterials can be applied to laboratory physical simulation experiments of overlying strata. It provides the basis for future research on large-scale physical water-containing similar simulation experiments.

A compact X-band correction cavity chain (CC) has been successfully designed, fabricated and high power tested for the Compact Linear Collider (CLIC) project. The CC consists of eight spherical cavities and four polarizers, and each spherical cavity has a Q_{0} of 45 000 and a diameter of 7 cm. The compact CC can correct a decaying pulse shape generated by a storage cavity without need of low efficiency pulse modulation or a solution based on long delay lines. A flattop output with small ripples can be obtained if the CC and the storage cavity are matched. Experiments of the CC with a barrel open cavity (BOC) were conducted on the XBOX2 test facility at CERN, and the high power results match the theoretical calculations. The appliance of the CC only reduces the pulse compression efficiency by 6% relatively if the transmission attenuation is ignored.

The Xian gamma-ray light source (XGLS) is a proposed novel high brightness gamma-ray source based on inverse Compton scattering (ICS) between the high brightness electron and laser beams. The photoinjector of the accelerator is one of the main components that determines the electron beam quality and related gamma-ray parameters [Phys. Rev. Accel. Beams 21, 030701 (2018)PRABCJ2469-988810.1103/PhysRevAccelBeams.21.030701; 20, 080701 (2017)PRABCJ2469-988810.1103/PhysRevAccelBeams.20.080701; 8, 100702 (2005)PRABFM1098-440210.1103/PhysRevSTAB.8.100702]. In order to reduce the risk of this project, a photoinjector including a laser-driven photocathode rf gun, two S-band tubes, and a diagnostic section was constructed and installed from 2016, serving as a pilot plant for the development of the key technologies for the projects. The injector is designed to deliver high quality electron bunches of typically 500 pC charge and ∼120 MeV energy with low emittance and jitter at 10 Hz repetition. Initial system commissioning with an electron beam was finished in the end of 2017, with a goal of a stable 0.6–0.7 mm mrad emittance in a 500-pC bunch clearly demonstrated. In this paper, we report the experimental results and experience obtained in the commissioning, including rf gun, drive laser system, timing and synchronization system, and beam diagnostics.

Choke-mode accelerating structures are higher-order-mode (HOM) damped structures that are relatively simple to fabricate and have low surface magnetic fields. C-band choke-mode accelerating structures have been successfully applied in free electron lasers. However, studies on X-band choke-mode structures for the main linac of the Compact Linear Collider (CLIC) currently remain at the theoretical design stage, and the high-gradient performance of a choke remains unknown. In this study, we designed and fabricated five different single-cell choke-mode accelerating structures and subjected them to high-gradient tests to study related radio frequency (rf) breakdown characteristics. High electrical field and small choke gap caused serious breakdowns in the choke, which mainly limited high-gradient performance. The choke-mode accelerating structure reached 121 MV/m at a breakdown rate of 8.30×10^{-4} per pulse per meter and a flat top pulse width of 250 ns. A new quantity proposed to give the high-gradient performance limitation of choke-mode accelerating structures due to rf breakdown. The new quantity was obtained from the summary of the high-gradient experiments and can be used as reference for high-gradient choke-mode accelerating structure design.

A prototype 11.994 GHz, traveling-wave accelerating structure for the Compact Linear Collider has been built, using the novel technique of assembling the structure from milled halves. The use of milled halves has many advantages when compared to a structure made from individual disks. These include the potential for a reduction in cost, because there are fewer parts, as well as a greater freedom in choice of joining technology because there are no rf currents across the halves’ joint. Here we present the rf design and fabrication of the prototype structure, followed by the results of the high-power test and post-test surface analysis. During high-power testing the structure reached an unloaded gradient of 100 MV/m at a rf breakdown rate of less than 1.5×10^{-5} breakdowns/pulse/m with a 200 ns pulse. This structure has been designed for the CLIC testing program but construction from halves can be advantageous in a wide variety of applications.

We present an X-band high-power pulse compression system for a klystron-based compact linear collider. In this system design, one rf power unit comprises two klystrons, a correction cavity chain, and two SLAC Energy Doubler (SLED)-type X-band pulse compressors (SLEDX). An rf pulse passes the correction cavity chain, by which the pulse shape is modified. The rf pulse is then equally split into two ways, each deploying a SLEDX to compress the rf power. Each SLEDX produces a short pulse with a length of 244 ns and a peak power of 217 MW to power four accelerating structures. With the help of phase-to-amplitude modulation, the pulse has a dedicated shape to compensate for the beam loading effect in accelerating structures. The layout of this system and the rf design and parameters of the new pulse compressor are described in this work.

Milling on two longitudinally split halves is one method to manufacture accelerating structures. This method is simple and allows one to avoid electromagnetic fields at bonding joints, making it attractive in manufacturing high-gradient accelerating structures. An X-band structure design with strong wakefield damping based on this manufacturing approach is studied in this work as an alternative design for the Compact Linear Collider (CLIC) main linac accelerating structures. The geometry of the structure is optimized to greatly reduce the surface fields, improve the efficiency, and suppress the wakefield. This structure features the baseline design of the CLIC main linac with additional advantages. This study may serve as a reference for designing other high frequency-band corrugated structures.

The Compact Linear Collider (CLIC) main linac uses waveguide damped structure as its baseline design. The current baseline structure design written in the CLIC Conceptual Design Report is named “CLIC-G.” Recent activities on the CLIC-G design including high power tests on structure prototypes and the study of machining cost assessment had raised the need of reoptimizing the structure design to minimize the machining cost and the pulse surface temperature rise. This work presents optimization of the structure geometry, high-order-mode (HOM) damping loads and the design of a HOM-free power splitter for the input coupler. Compared to the current baseline design CLIC-G, the new structure design reduced the pulse surface temperature rise, input power and manufacturing cost and achieves better suppression to the long range transverse wakefield. Cell disks and damping loads for the new structure design are also more compact than those of the CLIC-G design.

The X-band choke-mode structure is currently being studied as an alternative design for the accelerating structure of the compact linear collider (CLIC) main linac. The geometry of the choke-mode structure is designed to ensure the strong suppression of the beam-induced long-range transverse wakefield and therefore maintain the stability and quality of the beam in the CLIC main linac. Experiments conducted at the Argonne Wakefield Accelerator Facility are presented in this study to verify the design of the wakefield suppressor. The beam-induced radio frequency (rf) signals in a three-cell choke-mode structure were measured, and measured results show good agreement with the simulation results. The measured results also show strong damping in high-order dipolar modes with a quality factor Q of 10 to 20. The difference between the frequencies of the first and second dipole modes is about 3 GHz, which validates the special design of the cancelling dipole modes at the time of the succeeding bunch (0.5 ns).

The baseline design of CLIC (Compact Linear Collider) uses X-band accelerating structures for its main linacs. In order to maintain beam stability in multibunch operation, long-range transverse wakefields must be suppressed by 2 orders of magnitude between successive bunches, which are separated in time by 0.5 ns. Such strong wakefield suppression is achieved by equipping every accelerating structure cell with four damping waveguides terminated with individual rf loads. A beam-based experiment to directly measure the effectiveness of this long-range transverse wakefield and benchmark simulations was made in the FACET test facility at SLAC using a prototype CLIC accelerating structure. The experiment showed good agreement with the simulations and a strong suppression of the wakefields with an unprecedented minimum resolution of 0.1 V/(pC mm m).

C-band low-energy electron linear accelerators are preferable for applications which require compact structure and accurate positioning. During the past two years, the accelerator laboratory of Tsinghua University has developed a C-band 6 MeV standing-wave biperiodic on-axis coupled linear accelerator. The weight of the accelerator is 7.4 kg and the length is about 39 cm, which includes the thermal-cathode gun and the flange for tests. High capture ratio, narrow energy spectrum, and small spot size have been achieved in the high power rf test, which shows good performance of this accelerator and its great potential for industrial and medical applications.

Choke-mode damped structures are being studied as an alternative design to waveguide damped structures for the main linac of the Compact Linear Collider (CLIC). Choke-mode structures have the potential for lower pulsed temperature rise and simpler and less expensive fabrication. An equivalent circuit model based on transmission line theory for higher-order-mode damping is presented. Using this model, a new choke geometry is proposed and the wakefield performance is verified using Gdfidl. This structure has a comparable wakefield damping effect to the baseline design which uses waveguide damping. A prototype structure with the same iris dimensions and accelerating gradient as the nominal CLIC design, but with the new choke geometry, has been designed for high-power tests.

Introduction: Therapies targeting histone deacetylase (HDAC) have gained wider attention in the treatment of various clinical conditions. However, the use of HDAC inhibitors in pre-clinical trials in the case of Parkinson's disease (PD) is very limited. In the present study, the HDAC inhibitor, entinostat, was tested in animals induced with Parkinson's disease experimentally. Material and methods: Wistar male rats (150 ±10 g) were administered with rotenone (2 mg/kg/day, s.c.) for 21 days to induce PD, while entinostat (20 mg/kg) was given intraperitoneally. Then, the neurological functions, PD markers, and HDACs were analysed in the control and experimental animals. Results: The results demonstrated that rats that received entinostat displayed progressive motor, behavioural, and neurological function with attenuated α-synuclein and improved tyrosine-hydroxylase compared to control cells. Moreover, the induction of PD in rats demonstrated reduced levels of H2S, dopamine, 3, and 4-dihydroxyphenylacetic acid (DOPAC), and increased monoamine oxidase activity in PD rats. However, the rats that received entinostat demonstrated progressive levels of dopa and DOPAC, with attenuated levels of HDAC-2, -4, and -6 mRNA in the PD rats compared to controls. On the other hand, elevated (p < 0.01) levels of PD marker genes such as GDF3 and NMDA2b were reduced, with a significant increase in neuroprotective genes such as VDAC3 and CBX5 in entinostat-supplemented rats. Conclusions: The study results suggest that inhibition of HDAC systematically improves the neurological functions, and hence treatments, emphasizing that HDACI, as the speculated mechanism, will be a promising mode of treatment in PD. [ABSTRACT FROM AUTHOR]

Abstract Rosa laevigata is an excellent rose germplasm, highly resistant to aphid, and immune to both rose black spot and powdery mildew disease. It is also a well-known edible plant with a long history of medicinal use in China, having the effects of improving kidney function, inhibiting arteriosclerosis, and reducing inflammation. In this study, we assembled a high-quality chromosome-scale genome for R. laevigata by combining Illumina, PacBio, and Hi-C data, which has a length of approximately 494.2 Mb with a scaffold N50 of 68.6 Mb. A total of 493.2 Mb (99.8%) of the draft genome sequences were anchored on seven pseudochromosomes and two gapless pseudochromosomes were included in the final genome assembly. A total of 37,117 protein-coding genes were predicted, 34,047 of which were functionally annotated. Repeat annotation revealed 659,558 (285.6 Mb) repeat elements, accounting for 57.8% of the genome. The chromosome-scale genome provides valuable information to facilitate comparative genomic analysis of rose family and will accelerate genome-guided breeding and germplasm improvement of both R. laevigata itself and modern roses.

Abstract Background Bladder cancer (BC) is a malignant tumor. Methyltransferase-like 7B (MEETL7B) is a methyltransferase and its role in BC has not yet been revealed. Method Stable METTL7B knockdown or overexpression were achieved by lentiviral transduction in SW780 and TCCSUP cell lines. Xenografts tumors were established via subcutaneous injection of stable transfectants in BALB/c mice. Results A database search indicated that METTL7B was elevated in BC and it was validated in BC cell lines. METTL7B silencing suppressed cell proliferation and tumorigenesis in vitro and in vivo. Besides, METTL7B knockdown induced cell cycle arrest in G1 phase with a reduction in cyclin D1(CCND1), CDK4, and CDK6 levels and an elevation in CDKN2D levels in cells. Considering that ferroptosis is emerging as a therapeutic target for cancer, and the possible relationship between METTL7B and antioxidant enzymes. We, here, examined that ectopic METTL7B expression abolished ferroptosis markers in cells raised by Erastin treatment, including the production of lipid ROS, the increased cellular iron and MDA content, the decreased gene expression of ACSL3, FANCD2, and FADS2, as well as the mitochondrial injury observed by electron microscopy. Mechanically, ectopic METTL7B expression promoted m6A modification on ACSL3 mRNA. Gain of functional experiment exhibited that METTL7B inhibited Erastin-induced ferroptosis via ACSL3. Overexpressed PLAGL2 is identified as a possible independent predictor in BC and bioinformatics predicted the potential binding sites between PLAGL2 and METTL7B promoter region. Dual luciferase and chromatin immunoprecipitation analysis provided evidence that PLAGL2 directly binds to METTL7B promoter region. Conclusions METTL7B is involved in BC development and progression. METTL7B may mediate m6A modification on ACSL3 mRNA to negatively regulate ferroptosis in BC cells, which provides a potential therapeutic target for BC via ferroptosis. Graphical Abstract

Abstract Ozone is the primary air pollutant in eastern China during the warm season. Clarifying the differences in the spatio–temporal evolution of the ozone formation sensitivity between ozone polluted days and clean air days is key for the precise formulation of ozone prevention policies. By combining ground–and satellite–based remote sensing with ground station observations, we identified large spatio–temporal differences in the ozone formation sensitivity in eastern Chinese cities under different ozone pollution levels. Diurnally, the NO2 concentration was higher in the morning and lower at noon on the ozone exceedance days. The HCHO concentration was higher throughout the day, and the transition limited regime or NOx–limited regime contributed more to the ozone formation sensitivity on the ozone exceedance days. Vertically, the ratio of HCHO to NO2 (FNR) was higher on ozone exceedance days, and the contributions of NOx–limited regime at 0–2 km and the transition limited regime at 0–1 km on ozone exceedance days increased considerably. Spatially, HCHO in the North China Plain and middle–lower Yangtze River Plain was significantly increased on ozone exceedance days, while the NO2 concentration in the southeast hills was increased on ozone exceedance days. The difference in FNR values between northern and southern cities in eastern China on O3 exceedance days narrowed, and the ozone formation sensitivity in eastern China tended to be under a transition limited regime. The shifts in the ozone formation sensitivity under different ozone pollution levels implies that controlling only one of the precursors cannot achieve the best O3 prevention effect, and the most appropriate ratio of O3 precursor emission reductions should be designed according to ozone formation sensitivity in the different regions.

Abstract The purpose of this study is to evaluate the effectiveness of intensity-modulated radiation therapy (IMRT) combined with periorbital triamcinolone acetonide injection in treating thyroid eye disease (TED) patients with active extraocular muscle but low CAS. The retrospective observational study was conducted. A total of 156 eligible patients were selected from the TED patient database of the Ophthalmology Department of West China Hospital of Sichuan University. The patient’s relevant medical history was recorded, including gender, age of initial onset, onset eye, the interval between onset and the first visit to our hospital, extraocular muscle condition, smoking status, CAS, NOSPECS, thyroid function, symptoms and signs, and the condition of the affected extraocular muscle. We found that IMRT combined with periorbital triamcinolone acetonide injection has a good therapeutic effect on TED patients with low CAS but significant active extraocular muscles, and there is a significant improvement at 3 months after treatment. Thyroid function and CAS can affect the curative effect of IMRT. Patients with hyperthyroidism had worse effect than those with normal thyroid function. The higher the CAS, the better the effect.

Abstract Rheumatoid arthritis (RA), a form of autoimmune inflammation, is marked by enduring synovial inflammation and the subsequent impairment of joint function. Despite the availability of conventional treatments, they are often marred by significant side effects and the associated high costs. Plant-derived extracellular vesicles (PEVs) offer a compelling alternative, owing to their abundant availability, affordability, low immunogenicity, high biocompatibility, and feasibility for large-scale production. These vesicles enhance intercellular communication by transferring intrinsic bioactive molecules. In our research, we delve into the capacity of PEVs to treat RA, highlighting the role of ginger-derived extracellular vesicles (GDEVs). By conjugating GDEVs with folic acid (FA), we have developed FA-GDEVs that maintain their inherent immunomodulatory properties. FA-GDEVs are designed to selectively target M1 macrophages in inflamed joints via the folate receptors (FRs). Our in vitro findings indicate that FA-GDEVs promote the polarization towards a reparative M2 macrophage phenotype by modulating the PI3K-AKT pathway. Further corroboration comes from in vivo studies, which demonstrate that FA-GDEVs not only concentrate efficiently in the affected joints but also markedly reduce the manifestations of RA. Synthesizing these findings, it is evident that FA-GDEVs emerge as a hopeful candidate for RA treatment, offering benefits such as safety, affordability, and therapeutic efficacy. Graphical abstract

Bone-related diseases like osteoarthritis and osteoporosis impact millions globally, affecting quality of life. Osteoporosis considerably enhances the probability of bone fractures of the wrist, hip, and spine. Enhancement and acceleration of functional bone development can be achieved through the sustained delivery of growth factors (GFs) and cells in biomaterial carriers. The delivery of bioactive compounds in a targeted, spatiotemporal way that most closely resembles the natural defect repair process can be achieved by designing the carrier system with established release kinetics. Furthermore, the carrier can serve as a substrate that mimics the extracellular matrix, facilitating osteoprogenitor cell infiltration and growth for integrative tissue healing. In this report, we explore the significance of GFs within the realm of bone and cartilage tissue engineering, encompassing their encapsulation and delivery methodologies, the kinetics of release, and their amalgamation with biomaterials and stem cells (SCs) to facilitate the mending of bone fractures. Moreover, the significance of GFs in evaluating the microenvironment of bone tissue through reciprocal signaling with cells and biomaterial scaffolds is emphasized which will serve as the foundation for prospective advances in bone and cartilage tissue engineering as well as therapeutic equipment. Nanoparticles are being used in regenerative medicine to promote bone regeneration and repair by delivering osteoinductive growth factors like BMP-2, VEGF, TGF-β. These nanocarriers allow controlled release, minimizing adverse effects and ensuring growth factors are concentrated at the injury site. They are also mixed with mesenchymal stem cells (MSCs) to improve their engraftment, differentiation, and survival. This approach is a key step in developing multi-model systems that more efficiently facilitate bone regeneration. Researchers are exploring smart nanoparticles with immunomodulatory qualities to improve bonre regeneration and reduce inflammation in injury site. Despite promising preclinical results, challenges include cost management, regulatory approval, and long term safety. However, incorporating stem cell transport and growth factors in nanoparticles could revolutionize bone regeneration and offer more personalized therapies for complex bone disorders and accidents. The translational potential of this article: Stem cell transport and growth factors encapsulated in nanoparticles are becoming revolutionary methods for bone regeneration and repair. By encouraging stem cells to develop into osteoblasts, osteoinductive GFs like BMP-2, VEGF, and TGF-β can be delivered under control due to nanomaterials like nanoparticles, nanofibers, and nanotubes. By ensuring sustained release, these nanocarriers lessen adverse effects and enhance therapeutic results. In order to prove their survival and development, MCSs, which are essential for bone regeneration, are mixed with nanoparticles, frequently using scaffolds that resemble the ECM of bone. Furthermore, by adjusting to the injured environment and lowering inflammation, immunomodulatory nanostructures and stimuli-responsive nanomaterials can further maximize. While there are still shotcomings to overcome, including managing expenses, negotiating regulatory processes, and guaranteeing long-term safety, this method promises to outperform traditional bone grafting by providing quicker, more individualized, and more efficient treatments. Nano-embedded growth factors and stem cell technologies have the potential to revolutionize orthopedic therapy and significantly enhance patient outcomes with further research.

CuSn20P1 alloy has a wide range of applications in aerospace, automobile and other fields, but the mismatch between strength and plasticity in conventional casting has greatly limited its application field. In the paper, a melt enclosed cooling slope channel (ECSC) was used to prepare CuSn20P1 alloy semi-solid slurry, and then the casting was prepared by rheo-squeeze casting (RSC) and liquid squeeze casting (LSC). The effect of high mold temperature (500 °C, 525 °C, 550 °C, 575 °C) on peritectic phase content and properties of CuSn20P1 alloy was studied. The results show that the higher mold temperature is conducive to the formation of peritectic β phase, and the content of peritectic β phase increases from 36.18% to 57.88% with the mold temperature increasing from 500 °C to 575 °C. Interestingly, the δ-phase content decreased significantly with the increase in mold temperature. In addition, the β are tightly bound to the α-Cu and exist semi-coherent interface matching in (101) β//(-1-10) α-Cu. On the contrary, the β/δ interface is clear and well-bonded but no orientation relationship exists. The tensile strength and elongation increase from 282.9 MPa to 0.16% to 346.9 MPa and 0.26% with the mold temperature from 500 °C to 575 °C, respectively. The tensile strength and elongation of RSC at 575 °C are 29.3% and 116.7% higher than those of LSC-550, respectively. It is likely attributed to increased peritectic phase content with the semi-coherent interface, fine grain strengthening, and solid solution strengthening. Moreover, the fracture mechanism indicates that the peritectic phase can effectively prevent crack propagation. This work can make a significant contribution to the preparation of Cu alloy casting with high performance and high Sn content.

Abstract Unmanned aerial vehicle (UAV) path planning is a constrained multi-objective optimization problem. With the increasing scale of UAV applications, finding an efficient and safe path in complex real-world environments is crucial. However, existing particle swarm optimization (PSO) algorithms struggle with these problems as they fail to consider UAV dynamics, resulting in many infeasible solutions and poor convergence to optimal solutions. To address these challenges, we propose a spherical vector-based adaptive evolutionary particle swarm optimization (SAEPSO) algorithm. This algorithm, based on spherical vectors, directly incorporates UAV dynamic constraints and introduces improved tent map and reverse learning to enhance the diversity and distribution of initial solutions. Additionally, dynamic nonlinear and adaptive factors are integrated to balance exploration and exploitation capabilities. To avoid local optima in highly complex environments, we propose an adaptive acceleration strategy for poor particles, and an evolutionary programming strategy is incorporated to further improve the optimization capability. Finally, we conducted comparative studies and in six benchmark scenarios with varying threat levels, and the results demonstrated that the proposed algorithm outperforms others in the initial solution effectiveness, the final solution accuracy, convergence stability, and scalability.

Abstract Electric field induced antiferroelectric-ferroelectric phase transition is a double-edged sword for energy storage properties, which not only offers a congenital superiority with substantial energy storage density but also poses significant challenges such as large polarization hysteresis and poor efficiency, deteriorating the operation and service life of capacitors. Here, entropy increase effect is utilized to simultaneously break the long-range antiferroelectric order and locally adjust the fourfold commensurate modulated polarization configuration, leading to a breakthrough in the trade-off between recoverable energy storge density (14.8 J cm−3) and efficiency (90.2%) in medium-entropy antiferroelectrics. The embedding of non-polar phase regions in the incommensurate antiferroelectric matrices, revealing as a mixture of commensurate, incommensurate, and relaxor antiferroelectric polarization configurations, contributes to the diffuse antiferroelectric-ferroelectric phase transition, enhanced phase transition electric field, delayed polarization saturation, and efficient recovery of polarization. This work demonstrates that controlling local diverse antiferroelectric polarization configurations by increasing entropy is an effective avenue to develop high-performance energy storage antiferroelectrics, with implications that can be extended to other materials and functionalities.

Objective An important reason for the poor recovery of anterior cruciate ligament (ACL) injuries is the poor recovery of muscle function. Therefore, we used surface electromyography (sEMG) and gait analysis to explore the muscle activation patterns and gait characteristics between lower limbs under different exercise states in patients, following anterior cruciate ligament reconstruction (ACLR). Methods Forty‐one adults with unilateral ACL injuries in Binzhou Medical University Hospital from October 2022 to June 2023 were allocated to three groups according to the time after ACL reconstruction: group A (≤3 months, 16), group B (3 months–1 year, 13), and group C (>1 year, 12). Patients were tested by sEMG and gait, while straight leg raising (SLR), walking at normal speed, fast walking, and walking up and down the stairs. Two related sample tests were performed for the normalized root mean square (RMS) values and gait parameters. Results Muscle function changes varied in different training tasks. The RMS value of the involved side was more than the uninvolved side in biceps femoris and semitendinosus of group A (p

This paper presents a novel compact wideband quadruple-mode bandpass filter (BPF) with four resonant modes and five transmission zeros (TZs). Two T-shaped stepped impedance stub loaded resonators are coupled in parallel to the input and output feed lines to form the entire BPF. To provide a wideband and outstanding rejection in upper stopband, the two TZs are introduced by the stepped impedance stub as well as the designed coupling capacitor, and the two inherent TZs produced by the coupling between the resonators and feed lines are used and carefully tuned. The proposed BPF is fabricated in 65 nm CMOS technology with a core area of 0.072 mm2 (7.1×10-3 λ02). The measurement results show that the 3-dB bandwidth is 24.2 GHz at the center frequency of 94 GHz as well as the minimum insertion loss is 4.6 dB. Meanwhile, the stopband extends to 170 GHz with a stopband rejection above 25 dB.

In this work, a duplex-step rolling deformation, comprising single phase region rolling and dual phase region rolling, and three kinds of heat treatments were applied on an as-cast Ti-55511 alloy to enhance the mechanical properties. Tensile testing results show that a high tensile strength (∼1367 MPa) coupled with a decent ductility to failure (∼6.5%) can be obtained by the duplex-step heat treatment, including a high temperature heat treatment (930 °C) for a short time (3 min) followed by aging at a lower temperature (600 °C) for 120 min. Microstructure characterizations indicate that the high strength of the alloy can be attributed to the distribution of multi-scale α phase, and the good ductility of the alloy may stem from the existence of the Widmanstätten structure near the grain boundaries, which alleviates the strain localization between the grain boundary and the grain interior.

Blast furnace gas (BFG) is an important by-product energy for the iron and steel industry and has been widely used for heating or electricity generation. However, the undesirable contaminants in BFG (especially H2S) generate harmful environmental emissions. The desulfurization of BFG is urgent for integrated steel plants due to the stringent ultra-low emission standards. Compared with other desulfurization materials, zeolite-based adsorbents represent a viable option with low costs and long service life. In this study, an ammonia-induced CuO modified 13X adsorbent (NH3–CuO/13X) was prepared for H2S removal from simulated BFG at low temperature. The XRD, H2-TPR and TEM analysis proved that smaller CuO particles were formed and the dispersion of Cu on the surface of 13X zeolite was improved via the induction of ammonia. Evaluation on H2S adsorption performance of the adsorbent was carried out using simulated BFG, and the results showed that NH3–CuO/13X-3 has better breakthrough sulfur capacity, which was more than twice the sulfur capacity of CuO/13X. It is proposed that the enhanced desulfurization performance of NH3–CuO/13X is attributed to an abundant pore of 13X, and combined action of 13X and CuO. This work provided an effective way to improve the sulfur capacity of zeolite-based adsorbents via impregnation method by ammonia induction.

Abstract The relationship between hearing loss (HL) and Parkinson’s disease (PD) remains unclear. Using individual-level and summary-level data from the UK Biobank and the largest genome-wide association studies, we examined this link through observational, Mendelian randomization and genetic pleiotropy analyses. Among 158,229 participants, PD risk rose with HL severity especially in elder and males, and hearing aids significantly reduced PD risk in males. Although our results did not support a causal association, genetic correlation analysis suggested a localized genetic overlap (17q21.31). We identified 1545 SNPs and 63 genes with pleiotropic effects on HL and PD, including 79 novel SNPs across 6 loci, with 3 showing strong co-localization. These loci were enriched in key tissues like brain, heart, liver and pancreas, linked to the dihydrolipoyl dehydrogenase complex pathway, and targeted by drugs such as Warfarin and Phenprocoumon. Overall, this study reveals the risk association, genetic basis, and pleiotropic loci connecting HL and PD.

Abstract Background Specific molecular mechanisms by which AURKA promoted LSCC metastasis were still unknown. Methods Bioinformatic analysis was performed the relationship between TRIM28 and LSCC. Immunohistochemistry, Co-IP assay, Rt-PCR and Western Blot were used to examine the expression of related molecular. Flow cytometry was used to examine cell numbers of G0/G1 phase. Plate colony formation, wound healing, migration, invasion and tail vein injection in nude mice assays were applied to examine the proliferation, movement, migration, invasion and metastasis of LSCC. Results TRIM28 was significantly correlated with LSCC. TRIM28 highly expressed in LSCC and the high TRIM28 expression was related to TNM stage and poor clinical prognosis. Furthermore, AURKA could regulate TRIM28. In addition, deprivation TRIM28 expression induced LSCC cells into dormant state and inhibited LSCC metastasis. Akt signaling pathway played an essential role in promoting the tumor-promoting effects induced by TRIM28. Conclusion AURKA mediated TRIM28 to revive dormant LSCC cells via Akt signaling pathway to promote LSCC metastasis, targeting TRIM28 might provide a potential treatment strategy for LSCC.

Complex biological mechanisms and unidentified therapeutic targets for amyotrophic lateral sclerosis (ALS) significantly hinder the development of effective treatments. Given these challenges, reliable disease models that accurately replicate ALS phenotypes with relevant biological underpinnings are essential for advancing precision medicine in ALS. Patient-derived induced pluripotent stem cell (iPSC) organoids have emerged as an innovative tool for disease modeling and drug evaluation. Growing evidence highlights the advantages of organoids in replicating ALS phenotypes and supporting drug development. However, challenges remain in utilizing organoids for ALS drug testing and other neurodegenerative diseases. In this review we summarize the current progress in ALS model development, encompassing both in vitro and in vivo non-human models, as well as iPSC-derived human models. Furthermore, within the context of ALS drug screening, we discuss critical considerations for applying organoids to evaluate disease-associated phenotypes and to accurately reflect disease-related symptoms.

Internal solitary waves (ISWs) are extensively present in the Andaman Sea. Their generation and propagation can cause damage to offshore engineering structures and pose a threat to the safe navigation of submarines. Consequently, the ability to accurately predict ISWs is of considerable significance. This study addresses this challenge by analyzing the primary factors influencing ISWs propagation in the Andaman Sea, revealing that both water depth and stratification significantly affect propagation velocity. A CNN-LSTM hybrid neural network model, based on multiple features and the self-attention mechanism, has been constructed by incorporating the characteristics of ISWs (ISW-Attention-CNN-LSTM Net, IACL Net), aiming to predict the propagation of ISWs in the Andaman Sea. The dataset for this model was derived from Sentinel-1A ascending and descending orbit images of the Andaman Sea, spanning the years 2018–2023. From these, 864 images displaying clear ISWs characteristics were selected, resulting in the extraction of 5383 ISWs sample points along with their associated oceanic environmental parameters. The model utilizes the leading wavefront of the ISW wave packet as input to generate predictions of ISWs, which are subsequently compared with satellite observation data. The model's prediction results indicate that after one semidiurnal tidal cycle, the RMSE between the predicted dominant ISW wave crest and satellite observations is 3.891 km. Running the model over two semidiurnal tidal cycles produced similar results. Compared with other machine learning models, the prediction performance shows improvements across various metrics, demonstrating the model's robustness in predicting ISW.