Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition.

Cholecystokinin (CCK) enables excitatory circuit long-term potentiation (LTP). Here, we investigated its involvement in the enhancement of inhibitory synapses. Activation of GABA neurons suppressed neuronal responses in the neocortex to a forthcoming auditory stimulus in mice of both sexes. High-frequency laser stimulation (HFLS) of GABAergic neurons potentiated this suppression. HFLS of CCK interneurons could induce the LTP of their inhibition toward pyramidal neurons. This potentiation was abolished in CCK knock-out mice but intact in mice with both CCK1R and 2R knockout of both sexes. Next, we combined bioinformatics analysis, multiple unbiased cell-based assays, and histology examinations to identify a novel CCK receptor, GPR173. We propose GPR173 as CCK3R, which mediates the relationship between cortical CCK interneuron signaling and inhibitory LTP in the mice of either sex. Thus, GPR173 might represent a promising therapeutic target for brain disorders related to excitation and inhibition imbalance in the cortex.SIGNIFICANCE STATEMENT CCK, the most abundant and widely distributed neuropeptide in the CNS, colocalizes with many neurotransmitters and modulators. GABA is one of the important inhibitory neurotransmitters, and much evidence shows that CCK may be involved in modulating GABA signaling in many brain areas. However, the role of CCK-GABA neurons in the cortical microcircuits is still unclear. We identified a novel CCK receptor, GPR173, localized in the CCK-GABA synapses and mediated the enhancement of the GABA inhibition effect, which might represent a promising therapeutic target for brain disorders related to excitation and inhibition imbalance in the cortex.

Structural insights into the substrate binding sites of O-carbamoyltransferase VtdB from Streptomyces sp. NO1W98.

The O-carbamoyltransferase VtdB catalyzes the carbamoylation of venturicidin B, which is essential for the biosynthesis of the antibiotic venturicidin A. Here, the crystal structures of VtdB and VtdB in complex with the intermediate carbamoyladenylate (VtdBCAO) were determined at resolutions of 2.99 Å and 2.90 Å, respectively. The structures resemble the conserved YrdC-like and specific Kae1-like domains. A magnesium ion and the intermediate carbamoyladenylate were also observed in the Kae1-like domain of VtdB. The structure of VtdBCAO in complex with the substrate venturicidin B was modeled by a molecular docking method to better understand the substrate binding mode, revealing a novel venturicidin B binding pocket.

Thickness-dependent loss-induced failure of an ideal ENZ-enhanced optical response in planar ultrathin transparent conducting oxide films.

Ultrathin planar transparent conducting oxide (TCO) films are commonly used to enhance the optical response of epsilon-near-zero (ENZ) devices; however, our results suggest that thickness-dependent loss renders them ineffective. Here, we investigated the thickness-dependent loss of indium tin oxide (ITO) films and their effect on the ENZ-enhanced optical responses of ITO and ITO/SiO2 multilayer stacks. The experimental and computational results show that the optical loss of ITO films increases from 0.47 to 0.70 as the thickness decreases from 235 to 52 nm, which results in a reduction of 60% and 45% in the maximum field enhancement factor of a 52-nm monolayer ITO and 4-layer ITO/SiO2 multilayer stack, respectively. The experimental results show that the ENZ-enhanced nonlinear absorption coefficient of the 52-nm single-layer ITO film is -1.6 × 103 cm GW-1, which is 81% lower than that of the 235-nm ITO film (-8.6 × 103 cm GW-1), indicating that the thickness-dependent loss makes the ultrathin TCO films unable to obtain greater nonlinear responses. In addition, the increased loss reduces the cascading Berreman transmission valley intensity of the 4-layer ITO/SiO2 multilayer stack, resulting in a 42% reduction in the ENZ-enhanced nonlinear absorption coefficient compared to the 235-nm ITO film and a faster hot electron relaxation time. Our results suggest that the thickness and loss trade-off is an intrinsic property of TCO films and that the low-loss ultrathin TCO films are the key to the robust design and fabrication of novel ENZ devices based on flat ultrathin TCO films.

High-power femtosecond regenerative amplifier based on Yb:CaYAlO4 dual-crystal configuration.

A thermal lens insensitive regenerative amplifier (RA) with a dual Yb:CaYAlO4 (Yb:CYA) crystal configuration for extending gain spectra is demonstrated for the first time, to the best of our knowledge. By orthogonalizing the orientation of two a-cut Yb:CYA crystals in one RA, the Q switched spectrum with a full width at half maximum of 15.4 nm is generated, which is 1.5 and 1.6 times of the Q switched spectral bandwidth with π- and σ-polarization, respectively. With chirped pulses injection, this RA can deliver laser pulses with an average power exceeding 10 W at the repetition rate of 20-800 kHz and pulse energy of 1.5 mJ at 1 kHz. This is the highest average power from the Yb:CYA RA to the best of our knowledge. Finally, compressed pulses of 163 fs with 92% overall efficiency are realized. Thanks to the heat insensitive cavity design and excellent thermodynamic properties of the Yb:CYA crystal, the output laser beam is close to the diffraction limit with an M2 value of 1.07 × 1.07.

Structure-aware guided filtering for a ring artifact correction in synchrotron x-ray microtomography.

Synchrotron-based x-ray microtomography (S-µCT) is a powerful non-invasive three-dimensional (3D) imaging technique used for visualizing the internal structure of objects with micron-scale spatial resolution. However, in practical applications, ring artifacts often occur in S-µCT, which significantly degrades image quality and hinders interpretation. In this study, we propose a ring artifact correction method based on guided image filtering (GIF). The method first extracts structural prior from the input S-µCT images and then uses it as the guidance image to correct the ring artifacts. Finally, GIF with a self-guidance image is employed to further enhance image quality. Extensive comparisons and analyses on simulations and real data experiments demonstrate that the proposed method is capable of effectively correcting ring artifacts, accompanied by low-dose noise suppression and sparse-view artifact reduction. These findings suggest that the proposed method has great potential to promote the wider applications of S-µCT in the future.

Breathable and Stretchable Organic Electrochemical Transistors with Laminated Porous Structures for Glucose Sensing.

Dynamic glucose monitoring is important to reduce the risk of metabolic diseases such as diabetes. Wearable biosensors based on organic electrochemical transistors (OECTs) have been developed due to their excellent signal amplification capabilities and biocompatibility. However, traditional wearable biosensors are fabricated on flat substrates with limited gas permeability, resulting in the inefficient evaporation of sweat, reduced wear comfort, and increased risk of inflammation. Here, we proposed breathable OECT-based glucose sensors by designing a porous structure to realize optimal breathable and stretchable properties. The gas permeability of the device and the relationship between electrical properties under different tensile strains were carefully investigated. The OECTs exhibit exceptional electrical properties (gm ~1.51 mS and Ion ~0.37 mA) and can retain up to about 44% of their initial performance even at 30% stretching. Furthermore, obvious responses to glucose have been demonstrated in a wide range of concentrations (10-7-10-4 M) even under 30% strain, where the normalized response to 10-4 M is 26% and 21% for the pristine sensor and under 30% strain, respectively. This work offers a new strategy for developing advanced breathable and wearable bioelectronics.

Combined Prediction Model of Gas Concentration Based on Indicators Dynamic Optimization and Bi-LSTMs.

In order to accurately predict the gas concentration, find out the gas abnormal emission in advance, and take effective measures to reduce the gas concentration in time, this paper analyzes multivariate monitoring data and proposes a new dynamic combined prediction method of gas concentration. Spearman's rank correlation coefficient is applied for the dynamic optimization of prediction indicators. The time series and spatial topology features of the optimized indicators are extracted and input into the combined prediction model of gas concentration based on indicators dynamic optimization and Bi-LSTMs (Bi-directional Long Short-term Memory), which can predict the gas concentration for the next 30 min. The results show that the other gas concentration, temperature, and humidity indicators are strongly correlated with the gas concentration to be predicted, and Spearman's rank correlation coefficient is up to 0.92 at most. The average R2 of predicted value and real value is 0.965, and the average prediction efficiency R for gas abnormal or normal emission is 79.9%. Compared with the other models, the proposed dynamic optimized indicators combined model is more accurate, and the missing alarm of gas abnormal emission is significantly alleviated, which greatly improves the early alarming accuracy. It can assist the safety monitoring personnel in decision making and has certain significance to improve the safety production efficiency of coal mines.

Electroactive Microorganisms in Advanced Energy Technologies.

Large-scale production of green and pollution-free materials is crucial for deploying sustainable clean energy. Currently, the fabrication of traditional energy materials involves complex technological conditions and high costs, which significantly limits their broad application in the industry. Microorganisms involved in energy production have the advantages of inexpensive production and safe process and can minimize the problem of chemical reagents in environmental pollution. This paper reviews the mechanisms of electron transport, redox, metabolism, structure, and composition of electroactive microorganisms in synthesizing energy materials. It then discusses and summarizes the applications of microbial energy materials in electrocatalytic systems, sensors, and power generation devices. Lastly, the research progress and existing challenges for electroactive microorganisms in the energy and environment sectors described herein provide a theoretical basis for exploring the future application of electroactive microorganisms in energy materials.

Three New Benzophenone Derivatives from Selaginella tamariscina.

Six compounds including three new benzophenones, selagibenzophenones D-F (1-3), two known selaginellins (4-5) and one known flavonoid (6), were isolated from Selaginella tamariscina. The structures of new compounds were established by 1D-, 2D-NMR and HR-ESI-MS spectral analyses. Compound 1 represents the second example of diarylbenzophenone from natural sources. Compound 2 possesses an unusual biphenyl-bisbenzophenone structure. Their cytotoxicity against human hepatocellular carcinoma HepG2 and SMCC-7721 cells and inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compound 2 showed moderate inhibitory activity against HepG2 and SMCC-7721 cells, and compounds 4 and 5 showed moderate inhibitory activity to HepG2 cells. Compounds 2 and 5 also exhibited inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production.

Temporal contrast enhancement via nonlinear elliptical polarization rotation in a solid thin plate.

We demonstrate the simultaneous temporal contrast enhancement and spectral broadening via nonlinear elliptical polarization rotation in a solid thin plate. The efficiency, temporal contrast enhancement, spectral broadening, pulse compression and power stability are experimentally investigated. With this simple and efficient scheme, the temporal cleaned pulses with energy of 325 µJ and total efficiency of 30% are obtained. The temporal contrast and spectral bandwidth of the filtered pulse are 1011 and 104 nm, respectively. The pulse compressed from 180 fs to 45.8 fs is realized by utilizing chirped mirrors, corresponding to a compression factor of 3.93. With stable output power, presented scheme could be implemented in the ultra-intense femtosecond laser facilities.

Generation of 56.5 W femtosecond laser radiation by the combination of an Nd-doped picosecond amplifier and multi-pass-cell device.

We demonstrate the generation of high average power femtosecond laser radiation by combination of an Nd-doped picosecond amplifier and a multi-pass cell device. With this efficient and robust scheme, the pulse duration of a picosecond amplifier is compressed from 9.13 ps to 477 fs, corresponding to a compression factor of 19.1. The average power before and after pulse compression is 77 W and 56.5 W respectively, so the overall transmission reaches 73.4%. The presented scheme offers a viable route toward low-cost and simple configuration high power femtosecond lasers driven by Nd-doped picosecond amplifiers.

Cholecystokinin release triggered by NMDA receptors produces LTP and sound-sound associative memory.

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK-/- mice lacked neocortical LTP and showed deficits in a cue-cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue-cue associative memory.

Materials, Preparation Strategies, and Wearable Sensor Applications of Conductive Fibers: A Review.

The recent advances in wearable sensors and intelligent human-machine interfaces have sparked a great many interests in conductive fibers owing to their high conductivity, light weight, good flexibility, and durability. As one of the most impressive materials for wearable sensors, conductive fibers can be made from a variety of raw sources via diverse preparation strategies. Herein, to offer a comprehensive understanding of conductive fibers, we present an overview of the recent progress in the materials, the preparation strategies, and the wearable sensor applications related. Firstly, the three types of conductive fibers, including metal-based, carbon-based, and polymer-based, are summarized in terms of their principal material composition. Then, various preparation strategies of conductive fibers are established. Next, the primary wearable sensors made of conductive fibers are illustrated in detail. Finally, a robust outlook on conductive fibers and their wearable sensor applications are addressed.

Visuoauditory Associative Memory Established with Cholecystokinin Under Anesthesia Is Retrieved in Behavioral Contexts.

Plastic change in neuronal connectivity is the foundation of memory encoding. It is not clear whether the changes during anesthesia can alter subsequent behavior. Here, we demonstrated that in male rodents under anesthesia, a visual stimulus (VS) was associated with electrical stimulation of the auditory cortex or natural auditory stimulus in the presence of cholecystokinin (CCK), which guided the animals' behavior in a two-choice auditory task. Auditory neurons became responsive to the VS after the pairings. Moreover, high-frequency stimulation of axon terminals of entorhinal CCK neurons in the auditory cortex enabled LTP of the visual response in the auditory cortex. Such pairing during anesthesia also generated VS-induced freezing in an auditory fear conditioning task. Finally, we verified that direct inputs from the entorhinal CCK neurons and the visual cortex enabled the above neural plasticity in the auditory cortex. Our findings suggest that CCK-enabled visuoauditory association during anesthesia can be translated to the subsequent behavior action.SIGNIFICANCE STATEMENT Our study provides strong evidence for the hypothesis that cholecystokinin plays an essential role in the formation of cross-modal associative memory. Moreover, we demonstrated that an entorhinal-neocortical circuit underlies such neural plasticity, which will be helpful to understand the mechanisms of memory formation and retrieval in the brain.

Optimizing sub-nanosecond laser conditioning of DKDP crystals by varying the temporal shape of the pulse.

We propose a strategy to optimize the laser conditioning of DKDP crystals by varying the temporal shape of sub-nanosecond pulses. Four sub-ns temporally shaped pulses with nearly the same full width at half maxima of ∼600 ps but different rising-falling statuses were designed to conduct laser-induced damage (LID) and laser conditioning experiments on DKDP crystals. The shape of the pulse substantially influences the damage pinpoints size and LID threshold (LIDT) of the crystals in the sub-nanosecond range. After sub-nanosecond laser conditioning, the ns R-on-1 LIDT showed that slow-rising fast-falling pulse (R400-F200 and High-foot pulses) conditioning achieved a 14%-20% LIDT enhancement than the traditional Gaussian pulse (R300-F300 pulse). The 8-ns laser damage morphologies after slow-rising fast-falling pulse conditioning showed cracks, whereas those after fast-rising slow-falling pulse (R200-F400 pulse) conditioning were pinpoint core, as usual. These results suggest that the rising front plays an important role in the LID and laser conditioning of the DKDP crystals. A pulse with a slower rising front is beneficial for thermal modification, thereby leading to better LID properties. This strategy greatly expands and enriches the manipulation methods to improve the LIDT of DKDP crystals, and sheds light on understanding the laser damage mechanisms.

Few-cycle mid-infrared laser based on nonlinear self-compression in solid thin plates.

A few-cycle mid-infrared (MIR) laser is demonstrated via nonlinear self-compression in solid thin plates. In this novel solution, the anomalous material dispersion in the MIR band and the chirp induced by self-phase modulation are mutually compensated, which can achieve self-compression. Finally, with the 4 µm laser injection with 4.8 mJ/155 fs and few-cycle pulses with 3.44 mJ, 29.4 fs are generated with a high efficiency of 71.7%, and the system maintains very good spectral stability in 10 days. Compared with other post-compression methods, this self-compression technique has the advantages of high efficiency and robust and large energy expansion scale, which can be further extended to MIR lasers with other wavelengths and higher peak power.

Broad-bandwidth high-temporal-contrast carrier-envelope-phase-stabilized laser seed for 100 PW lasers.

We demonstrate in this Letter the generation of carrier-envelope-phase (CEP)-stabilized laser pulses at 910 nm with simultaneously high-temporal-contrast, broad spectral bandwidths and few-cycle pulse durations. Through combining the techniques of cascaded optical parametric amplification (OPA) and second-harmonic generation (SHG) in the laser setup, a pulse temporal contrast as high as ${ \gt }{{10}^{12}}$>1012 has been obtained at the laser output. During the OPA and SHG processes, both the pulse chirp and gain bandwidth are perfectly optimized, leading to the generation of 170 µJ pulses with ${ \gt }{200}\;{\rm nm}$>200nm bandwidth and ${\sim}{15}\;{\rm fs}$∼15fs pulse duration. Moreover, the CEP of the laser is stabilized passively to a noise level of less than 340 mrad. This high-quality pulsed light source, as the seed laser of the deuterated potassium dihydrogen phosphate (DKDP)-based 100 PW system, will be integrated into the Station of Extreme Light facility in the near future.

Electrochemical Reduction of Carbon Dioxide to 1-Butanol on Oxide-Derived Copper.

The electroreduction of carbon dioxide using renewable electricity is an appealing strategy for the sustainable synthesis of chemicals and fuels. Extensive research has focused on the production of ethylene, ethanol and n-propanol, but more complex C4 molecules have been scarcely reported. Herein, we report the first direct electroreduction of CO2 to 1-butanol in alkaline electrolyte on Cu gas diffusion electrodes (Faradaic efficiency=0.056 %, j1-Butanol =-0.080 mA cm-2 at -0.48 V vs. RHE) and elucidate its formation mechanism. Electrolysis of possible molecular intermediates, coupled with density functional theory, led us to propose that CO2 first electroreduces to acetaldehyde-a key C2 intermediate to 1-butanol. Acetaldehyde then undergoes a base-catalyzed aldol condensation to give crotonaldehyde via electrochemical promotion by the catalyst surface. Crotonaldehyde is subsequently electroreduced to butanal, and then to 1-butanol. In a broad context, our results point to the relevance of coupling chemical and electrochemical processes for the synthesis of higher molecular weight products from CO2 .

Multipass active stretcher with large chirp for high-flux ultra-intense lasers.

We demonstrate a novel active multipass stretcher that can deliver pulses with large chirp, adjustable chirped pulse duration, and great beam quality for a high-flux chirped-pulse amplification system. The stretcher is based on a Martinez-type stretcher and a regenerative amplifier structure, and the laser pulses can be amplified while they are stretched in the cavity. By controlling the round trip of the pulses running in the cavity, chirped pulses with more than 10 ns, even scaling to 30 ns, pulse duration and 20 nm bandwidth can be obtained very easily, which indicates a chirp rate of 0.5 ns/nm at 1053 nm central wavelength. Chirped pulses with several millijoules energy can be delivered with an Nd:glass-based intracavity amplifier used to compensate the losses. Benefited by the advantage of regenerative structure, the output pulses have excellent beam quality with M2 of 1.1. Finally, the chirped pulses from this novel stretcher are compressed to 1.13 times the Fourier transform limit. With these advantages, this novel multipass active stretcher is significant for ultra-intense laser systems, especially for high-flux and high-energy 100 petawatt lasers.