Minimizing Task Age upon Decision for Low-Latency MEC Networks Task Offloading with Action-Masked Deep Reinforcement Learning.

In this paper, we consider a low-latency Mobile Edge Computing (MEC) network where multiple User Equipment (UE) wirelessly reports to a decision-making edge server. At the same time, the transmissions are operated with Finite Blocklength (FBL) codes to achieve low-latency transmission. We introduce the task of Age upon Decision (AuD) aimed at the timeliness of tasks used for decision-making, which highlights the timeliness of the information at decision-making moments. For the case in which dynamic task generation and random fading channels are considered, we provide a task AuD minimization design by jointly selecting UE and allocating blocklength. In particular, to solve the task AuD minimization problem, we transform the optimization problem to a Markov Decision Process problem and propose an Error Probability-Controlled Action-Masked Proximal Policy Optimization (EMPPO) algorithm. Via simulation, we show that the proposed design achieves a lower AuD than baseline methods across various network conditions, especially in scenarios with significant channel Signal-to-Noise Ratio (SNR) differences and low average SNR, which shows the robustness of EMPPO and its potential for real-time applications.

Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic dermatitis-like inflammation.

BACKGROUND: Meteorin-like protein (METRNL)/Interleukin-41 (IL-41) is a novel immune-secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD). METHODS: METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903-induced AD-like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single-cell RNA-seq and RNA-seq. RESULTS: METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced ß-Catenin activation, limited the expression of Th2-related molecules that attract the accumulation of Arginase-1 (Arg1)hi macrophages, dendritic cells, and activated mast cells. CONCLUSIONS: METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule ß-Catenin.

Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in H2O2-challenged KGN human granulosa cell line.

BACKGROUND: Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. METHODS: In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. RESULTS: The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. CONCLUSIONS: The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.

Face-to-face Assembly Strategy of Au Nanocubes: Induced Generation of Broad Hotspot Regions for SERS-Fluorescence Dual-Signal Detection of Intracellular miRNAs.

While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.

Structural and Compositional Changes in Two Marine Shell Traditional Chinese Medicines: A Comparative Analysis Pre- and Post-Calcination.

BACKGROUND: Arcae concha and Meretricis concha cyclinae concha are two marine shellfish herbs with similar composition and efficacy, which are usually calcined and used clinically. OBJECTIVE: This study investigated variations in the inorganic and organic components of Arcae concha and Meretricis concha cyclinae concha from different production regions, both Arcae concha and Meretricis concha cyclinae concha. The aim was to enhance the understanding of these two types of marine shell traditional Chinese medicine (msTCM) and provide a foundation for their future development and application. METHOD: Spectroscopic techniques, including infrared spectroscopy, X-ray spectroscopy, and X-ray fluorescence spectroscopy, were used to analyze the calcium carbonate (CaCO3) crystal and trace elements. Thermogravimetric analysis was used to investigate the decomposition process during heating. The proteins were quantified using the BCA protein assay kit. Principal component analysis (PCA) was used to classify inorganic elements in the two marine shellfish traditional Chinese medicines. RESULTS: No significant differences among the various production regions. The crystal structure of CaCO3 in the raw products was aragonite, but it transformed into calcite after calcination. The contents of Ca, Na, Sr, and other inorganic elements were highest. The protein content was significantly reduced after calcination. Therefore, these factors cannot accurately reflect the internal quality of TCM, rendering qualitative identification challenging. CaCO3 dissolution in the decoction of Arcae concha and Meretricis concha cyclinae concha increased after calcination, aligning with the clinical application of calcined shell TCM. PCA revealed the inorganic elements in them, indicating that the variation in trace element composition among different drugs leads to differences in their therapeutic focus, which should be considered during usage. CONCLUSION: This study clarified the composition and structure changes of corrugated and clam shell before and after calcining, and laid the foundation for the comprehensive utilization of Marine traditional Chinese medicine. HIGHLIGHTS: These technical representations reveal the differences between raw materials and processed products, which will provide support for the quality control of other shellfish TCMS.

l-arginine and l-lysine supplementation to NaCl tenderizes porcine meat by promoting myosin extraction and actomyosin dissociation.

This study investigated the individual and combined effects of l-arginine, l-lysine, and NaCl on the ultrastructure of porcine myofibrils to uncover the mechanism underlying meat tenderization. Arg or Lys alone shortened A-bands and damaged M-lines, while NaCl alone destroyed M- and Z-lines. Overall, Arg and Lys cooperated with NaCl to destroy the myofibrillar ultrastructure. Moreover, these two amino acids conjoined with NaCl to increase myosin solubility, actin band intensity, and the protein concentration of the actomyosin supernatant. However, they decreased the turbidity and particle size of both myosin and actomyosin solutions, and the remaining activities of Ca2+- and Mg2+-ATPase. The current results revealed that Arg/Lys combined with NaCl to extract myosin and dissociate actomyosin, thereby aggravating the destruction of the myofibrillar ultrastructure. The present results provide a good explanation for the previous phenomenon that Arg and Lys cooperated with NaCl to improve meat tenderness.

Native Approach to Controlled-Z Gates in Inductively Coupled Fluxonium Qubits.

The fluxonium qubits have emerged as a promising platform for gate-based quantum information processing. However, their extraordinary protection against charge fluctuations comes at a cost: when coupled capacitively, the qubit-qubit interactions are restricted to XX interactions. Consequently, effective ZZ or XZ interactions are only constructed either by temporarily populating higher-energy states, or by exploiting perturbative effects under microwave driving. Instead, we propose and demonstrate an inductive coupling scheme, which offers a wide selection of native qubit-qubit interactions for fluxonium. In particular, we leverage a built-in, flux-controlled ZZ interaction to perform qubit entanglement. To combat the increased flux-noise-induced dephasing away from the flux-insensitive position, we use a continuous version of the dynamical decoupling scheme to perform noise filtering. Combining these, we demonstrate a 20 ns controlled-z gate with a mean fidelity of 99.53%. More than confirming the efficacy of our gate scheme, this high-fidelity result also reveals a promising but rarely explored parameter space uniquely suitable for gate operations between fluxonium qubits.

Multielement simultaneous quantitative analysis of trace elements in stainless steel via full spectrum laser-induced breakdown spectroscopy.

Laser-Induced Breakdown Spectroscopy (LIBS) instruments are increasingly recognized as valuable tools for detecting trace metal elements due to their simplicity, rapid detection, and ability to perform simultaneous multi-element analysis. Traditional LIBS modeling often relies on empirical or machine learning-based feature band selection to establish quantitative models. In this study, we introduce a novel approach-simultaneous multi-element quantitative analysis based on the entire spectrum, which enhances model establishment efficiency and leverages the advantages of LIBS. By logarithmically processing the spectra and quantifying the cognitive uncertainty of the model, we achieved remarkable predictive performance (R2) for trace elements Mn, Mo, Cr, and Cu (0.9876, 0.9879, 0.9891, and 0.9841, respectively) in stainless steel. Our multi-element model shares features and parameters during the learning process, effectively mitigating the impact of matrix effects and self-absorption. Additionally, we introduce a cognitive error term to quantify the cognitive uncertainty of the model. The results suggest that our approach has significant potential in the quantitative analysis of trace elements, providing a reliable data processing method for efficient and accurate multi-task analysis in LIBS. This methodology holds promising applications in the field of LIBS quantitative analysis.

The modern scientific mystery of traditional Chinese medicine processing--take some common traditional Chinese medicine as examples.

The processing of traditional Chinese medicine (TCM) is a unique traditional pharmaceutical technology in China, which is the most important feature that distinguishes Chinese medicine from natural medicine and plant medicine. Since the record in Huangdi Neijing (Inner Canon of the Yellow Emperor), till now, the processing of TCM has experienced more than 2000 years of inheritance, innovation, and development, which is a combination of TCM theory and clinical practice, and plays an extremely important position in the field of TCM. In recent years, as a clinical prescription of TCM, Chinese herbal pieces have played a significant role in the prevention and control of the COVID-19 and exhibited their unique value, and therefore they have become the highlight of China's clinical treatment protocol and provided Chinese experience and wisdom for the international community in the prevention and control of the COVID-19 epidemic. This paper outlines the research progress in the processing of representative TCM in recent years, reviews the mechanism of the related effects of TCM materials after processing, such as changing the drug efficacy and reducing the toxicity, puts forward the integration and application of a variety of new technologies and methods, so as to reveal the modern scientific mystery of the processing technology of TCM.

Emergence of plasmid-mediated high-level tigecycline resistance gene tet(X4) in Enterobacterales from retail aquatic products.

The spread of antimicrobial-resistant microbes and genes in various foods poses a significant threat to public health. Of particular global concern is the plasmid-mediated tigecycline resistance gene tet(X4), which, while identified in various sources, has not hitherto been reported in aquatic products. This study aimed to investigate the occurrence and characterization of tigecycline-resistant strains from aquatic products. A total of 73 nonrepetitive seafood samples were purchased from 26 farmers' markets to detect tigecycline-resistant strains. Of these, nine Escherichia coli strains (comprising two ST58, one ST195, ST10, ST48, ST88, ST877, ST1244, ST14462) and one Citrobacter meridianamericanus, recovered from nine (12.33 %, 9/73) seafood samples (fish, n = 7; shrimp, clam and crab, n = 1 respectively), were positive for the tet(X4). Notably, phylogenetic analysis showed that E. coli ST195, a common ST carrying tet(X4), has a close phylogenetic relationship (23∼48 SNPs) with 32 tet(X4)-harboring E. coli ST195 isolates (isolated from pigs, animal foods, vegetable, and humans) deposited in NCBI database. Additionally, E. coli ST58 was closely (2 SNPs) related to one tet(X4)-positive E. coli strain from retail vegetables documented in the NCBI database. Whole genome sequencing and bioinformatic analysis revealed that tet(X4) genes were located on IncX1 (7 E. coli) or hybrid plasmid IncFIA(HI1)/IncHI1B(R27)/IncHI1A (2 E.coli and one C. meridianamericanus). These plasmids displayed high homology with those of plasmids from other sources deposited in GenBank database. These findings underscore the role of epidemic clones and plasmids in driving the dissemination of tet(X4) gene within Enterobacterales of aquatic products origin. To the best of our knowledge, this is the first report of tet(X4)-positive Enterobacterales from aquatic products. The pervasive propagation of tet(X4) gene facilitated by epidemic plasmids and clones across food animals, food products, humans, and the environment presents a serious threat to public health.

Tuning Reactive Crystallization Pathways for Integrated CO2 Capture, Conversion, and Storage via Mineralization.

ConspectusAchieving carbon neutrality requires realizing scalable advances in energy- and material-efficient pathways to capture, convert, store, and remove anthropogenic CO2 emission in air and flue gas while cogenerating multiple high-value products. To this end, earth-abundant Ca- and Mg-bearing alkaline resources can be harnessed to cogenerate Ca- and Mg-hydroxide, silica, H2, O2, and a leachate bearing high-value metals in an electrochemical approach with the in situ generation of a pH gradient, which is a significant departure from existing pH-swing-based approaches. To accelerate CO2 capture and mineralization, CO2 in dilute sources is captured using solvents to produce CO2-loaded solvents. CO2-loaded solvents are reacted Ca- and Mg-bearing hydroxides to produce Ca- and Mg-carbonates while regenerating the solvents. These carbonates can be used as a temporary or permanent store of CO2 emissions. When carbonates are used as a temporary store of CO2 emissions, electrochemical sorbent regeneration pathways can be harnessed to produce high-purity CO2 while regenerating Ca- and Mg-hydroxide and coproducing H2 and O2. Figure 1 is a schematic representation of this integrated approach.Tuning the molecular-scale and nanoscale interactions underlying these reactive crystallization mechanisms for carbon transformations is crucial for achieving kinetic, chemical, and morphological controls over these pathways. To this end, the feasibility of (i) crystallizing Ca- and Mg-hydroxide during the electrochemical desilication of earth-abundant alkaline industrial residues, (ii) accelerating the conversion of Ca- and Mg-carbonates for temporary or permanent carbon storage by harnessing regenerable solvents, and (iii) regenerating Ca- and Mg-hydroxide while coproducing high-purity CO2, O2, and H2 electrochemically is established.Evidence of the fractionation of heterogeneous slag to coproduce silica, Ca- and Mg-hydroxide, and a leachate bearing metals during electrochemical desilication provides the basis for further tuning the physicochemical parameters to improve the energy and material efficiency of these pathways. To address the slow kinetics of CO2 capture and mineralization starting from ultradilute emissions, reactive capture pathways that harness solvents such as Na-glycinate are shown to be effective. The extents of carbon mineralization of Ca(OH)2 and Mg(OH)2 are 97% and 78% using CO2-loaded Na-glycinate upon reacting for 3 h at 90 °C. During the regeneration of Ca- and Mg-hydroxide and high-purity CO2 from carbonate sources, charge efficiencies of as high as 95% were observed for the dissolution of MgCO3 and CaCO3 while stirring at 100 rpm. Higher yields of Mg(OH)2 are observed compared to that for Ca(OH)2 during sorbent regeneration due to the lower solubility of Mg(OH)2. These findings provide the scientific basis for further tuning these reactive crystallization pathways for closing material and carbon cycles to advance a sustainable climate, energy, and environmental future.

Myofibrillar proteins' intermolecular interaction weakening and degradation: Are they mainly responsible for the tenderization of meat containing l-arginine, l-lysine, or/and NaCl?

This study explored the effects of l-arginine, l-lysine, and NaCl alone and in combination on the tenderness of porcine meat. Arg, Lys, and NaCl alone improved the tenderness, decreased the cooking loss, and increased the myofibrillar fragmentation index (MFI) of porcine meat; Both Arg and Lys cooperated with NaCl to better achieve this effect. Furthermore, Arg/Lys collaborated with NaCl to increase muscle fiber swelling and moisture content of the meat and promoted the extraction of main myofibrillar proteins. FT-IR revealed that Arg, Lys, or NaCl alone or in combination caused changes in protein-water interactions. Western blotting revealed varying degrees of meat protein degradation in all cases, but the results did not well coincide with those of shear force and the MFI. Therefore, the weakening of intermolecular forces between myofibrillar proteins was considered the main reason for meat tenderization under the present study conditions.

Logical quantum processor based on reconfigurable atom arrays.

Suppressing errors is the central challenge for useful quantum computing1, requiring quantum error correction (QEC)2-6 for large-scale processing. However, the overhead in the realization of error-corrected 'logical' qubits, in which information is encoded across many physical qubits for redundancy2-4, poses substantial challenges to large-scale logical quantum computing. Here we report the realization of a programmable quantum processor based on encoded logical qubits operating with up to 280 physical qubits. Using logical-level control and a zoned architecture in reconfigurable neutral-atom arrays7, our system combines high two-qubit gate fidelities8, arbitrary connectivity7,9, as well as fully programmable single-qubit rotations and mid-circuit readout10-15. Operating this logical processor with various types of encoding, we demonstrate improvement of a two-qubit logic gate by scaling surface-code6 distance from d = 3 to d = 7, preparation of colour-code qubits with break-even fidelities5, fault-tolerant creation of logical Greenberger-Horne-Zeilinger (GHZ) states and feedforward entanglement teleportation, as well as operation of 40 colour-code qubits. Finally, using 3D [[8,3,2]] code blocks16,17, we realize computationally complex sampling circuits18 with up to 48 logical qubits entangled with hypercube connectivity19 with 228 logical two-qubit gates and 48 logical CCZ gates20. We find that this logical encoding substantially improves algorithmic performance with error detection, outperforming physical-qubit fidelities at both cross-entropy benchmarking and quantum simulations of fast scrambling21,22. These results herald the advent of early error-corrected quantum computation and chart a path towards large-scale logical processors.

Infusing phytate-based biomass flame retardants into the cellulose lumens of Chinese fir wood attains superior flame retardant efficacy.

To be suitable for certain construction and furniture applications, wood must be treated with a flame retardant and impregnating flame retardants into the cellulose lumens of wood is an effective flame retardant method. Phytic acid, the main storage form of phosphorus in various plant tissues, is an inexpensive, and non-toxic biomaterial that shows potential applications as an environmentally friendly bio-based flame retardant. In this study, phytic acid and zinc phytate were used to impregnate delignified wood under vacuum and pressure, which greatly enhanced the flame retardancy and smoke suppression properties of Chinese fir, while still maintaining its original texture. Phytic acid and zinc phytate were hydrogen-bonded to cellulose in wood. Phytic acid and zinc phytate were hydrogen-bonded to cellulose in wood. The results showed that the total heat release (THR) of Chinese fir treated with zinc phytate decreased from 55.66 MJ/m2 to 5.90 MJ/m2, and a compact carbonized protective layer was quickly formed on the surface of Chinese fir after ignition. Thermogravimetric analysis (TGA) showed that the char yield of Chinese fir treated by the flame retardant was 177.6 % higher than that of untreated wood. This study provides an efficient, sustainable, and economical method to prepare Chinese fir with excellent flame retardancy and thermal insulation performance.

Density Functional Theory and Raman Spectroscopy Studies of Adsorption Sites of Au Nanoparticles with Alectinib.

Alectinib is an ALK tyrosine kinase inhibitor, which is mainly used in patients with crizotinib-resistant nonsmall cell lung cancer. Alectinib has attracted much clinical attention for its longest progression-free survival time and the best therapeutic effect. The chemical adsorption of Au nanoclusters (AuNPs) with alectinib molecules is studied by density functional theory (DFT) and surface-enhanced Raman scattering spectroscopy (SERS) experiments. DFT/B3LYP-D3/6-311G** was used for optimization and vibration analysis of alectinib-Au6 complexes, as well as molecular electrostatic potential, frontier molecular orbital, and electro-optic-based charge transfer descriptors. Comparing the results of the DFT theory and SERS experiment, alectinib and AuNPs can form Au-N6 bonds primarily through chemical adsorption of N6 atoms, and the experimental results showed that the enhancement factor (EFCHEM) could reach 4.27. The results provide a theoretical basis for exploring the mechanism of chemical enhancement between AuNPs and alectinib.

Occurrence and characterization of NDM-5-producing Escherichia coli from retail eggs.

The New Delhi Metallo-ß-lactamase (NDM) producing Enterobacterales has been detected from diverse sources but has rarely been reported in retail eggs. In this study, 144 eggshell and 96 egg content samples were collected in 2022 from Guangdong province and were screened for NDM-producing strains. Four Escherichia coli strains (ST3014, ST10, ST1485, and ST14747) recovered from two (1.39%, 2 of 144) eggshells and two (2.08%, 2 of 96) egg content samples were identified as blaNDM-5-positive strains. Oxford Nanopore MinION sequencing and conjugation assays revealed that the blaNDM-5 gene was carried by IncX3 (n = 1), IncI1 (n = 1), and IncHI2 (n = 2). The IncI1-plasmid-carrying blaNDM-5 displayed high homology with one plasmid pEC6563-NDM5 from the human clinic, while the IncHI2 plasmid harboring blaNDM-5 shared highly similar structures with plasmids of animal origin. To the best of our knowledge, this is the first report on the identification of blaNDM-5-positive bacteria in retail eggs. NDM-producing E. coli could be transmitted to humans by the consumption of eggs or direct contact, which could pose a potential threat to human health.

Engineered domain-inlaid Nme2Cas9 adenine base editors with increased on-target DNA editing and targeting scope.

BACKGROUND: Nme2ABE8e has been constructed and characterized as a compact, accurate adenine base editor with a less restrictive dinucleotide protospacer-adjacent motif (PAM: N4CC) but low editing efficiency at challenging loci in human cells. Here, we engineered a subset of domain-inlaid Nme2Cas9 base editors to bring the deaminase domain closer to the nontarget strand to improve editing efficiency. RESULTS: Our results demonstrated that Nme2ABE8e-797 with adenine deaminase inserted between amino acids 797 and 798 has a significantly increased editing efficiency with a wide editing window ranging from 4 to 18 bases in mammalian cells, especially at the sites that were difficult to edit by Nme2ABE8e. In addition, by swapping the PAM-interacting domain of Nme2ABE8e-797 with that of SmuCas9 or introducing point mutations of eNme2-C in Nme2ABE8e-797, we created Nme2ABE8e-797Smu and Nme2ABE8e-797-C, respectively, which exhibited robust activities at a wide range of sites with N4CN PAMs in human cells. Moreover, the modified domain-inlaid Nme2ABE8e can efficiently restore or install disease-related loci in Neuro-2a cells and mice. CONCLUSIONS: These novel Nme2ABE8es with increased on-target DNA editing and expanded PAM compatibility will expand the base editing toolset for efficient gene modification and therapeutic applications.

Unraveling the parameters and biological mechanisms of CO2 laser therapy for acute pain relief.

Acute pain-related pathology is a significant challenge in clinical practice, and the limitations of traditional pain-relief drugs have made it necessary to explore alternative approaches. Photobiomodulation (PBM) therapy using CO2 laser has emerged as a promising option. In this study, we aimed to identify the optimal parameters of CO2 laser irradiation for acute pain relief through in vivo and in vitro experiments. First, we validated the laser intensity used in this study through bone marrow mesenchymal stem cells (BMSCs) experiments to ensure it will not adversely affect stem cell viability and morphology. Then we conducted a detailed evaluation of the duty cycle and frequency of CO2 laser by the hot plate and formalin test. Results showed a duty cycle of 3% and a frequency of 25 kHz produced the best outcomes. Additionally, we investigated the potential mechanisms underlying the effects of CO2 laser by immunohistochemical staining, and found evidence to suggest that the opioid receptor may be involved in its analgesic effect. In conclusion, this study provides insights into the optimal parameters and underlying mechanisms of CO2 laser therapy for effective pain relief, thereby paving the way for future clinical applications.

Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process.

Interleukin-37 (IL-37) is a newly discovered member of IL-1 family. The cytokine was proved to have extensive protective effects in infectious diseases, allergic diseases, metabolic diseases, autoimmune diseases and tumors since its discovery. IL-37 was mainly produced by immune and some non-immune cells in response to inflammatory stimulus. The IL-37 precursors can convert into the mature forms after caspase-1 cleavage and activation intracellularly, and then bind to Smad-3 and transfer to the nucleus to inhibit the production and functions of proinflammatory cytokines; extracellularly, IL-37 binds to cell surface receptors to form IL-37/IL-18Rα/IL-1R8 complex to exert immunosuppressive function via inhibiting/activating multiple signal pathways. In addition, IL-37 can attenuate the pro-inflammatory effect of IL-18 through directly or forming an IL-37/IL-18BP/IL-18Rß complex. Therefore, IL-37 has the ability to suppress innate and acquired immunity of the host, and effectively control inflammatory stimulation, which was considered as a new hallmark of cancer. Specifically, it is concluded that IL-37 can inhibit the growth and migration of tumor cells, prohibit angiogenesis and mediate the immunoregulation in tumor microenvironment, so as to exert effective anti-tumor effects. Importantly, latest studies also showed that IL-37 may be a novel therapeutic target for cancer monitoring. In this review, we summarize the immunoregulation roles and mechanisms of IL-37 in anti-tumor process, and discuss its progress so far and potential as tumor immunotherapy.

Development of a highly efficient prime editor system in mice and rabbits.

The recently developed prime-editing (PE) technique is more precise than previously available techniques and permits base-to-base conversion, replacement, and insertions and deletions in the genome. However, previous reports show that the efficiency of prime editing is insufficient to produce genome-edited animals. In fact, prime-guide RNA (pegRNA) designs have posed a challenge in achieving favorable editing efficiency. Here, we designed prime binding sites (PBS) with a melting temperature (Tm) of 42 °C, leading to optimal performance in cells, and we found that the optimal Tm was affected by the culture temperature. In addition, the ePE3max system was developed by updating the PE architecture to PEmax and expressing engineered pegRNA (epegRNA) based on the original PE3 system. The updated ePE3max system can efficiently induce gene editing in mouse and rabbit embryos. Furthermore, we successfully generated a Hoxd13 (c. 671 G > T) mutation in mice and a Tyr (c. 572 del) mutation in rabbits by ePE3max. Overall, the editing efficiency of modified ePE3max systems is superior to that of the original PE3 system in producing genome-edited animals, which can serve as an effective and versatile genome-editing tool for precise genome modification in animal models.