The neurophysiological mechanisms of medial prefrontal-perirhinal cortex circuit mediating temporal order memory decline in early stage of AD rats.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.

Deciphering spatial domains from spatial multi-omics with SpatialGlue.

Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize the full potential of such data, we need spatially informed methods for data integration. Here, we introduce SpatialGlue, a graph neural network model with a dual-attention mechanism that deciphers spatial domains by intra-omics integration of spatial location and omics measurement followed by cross-omics integration. We demonstrated SpatialGlue on data acquired from different tissue types using different technologies, including spatial epigenome-transcriptome and transcriptome-proteome modalities. Compared to other methods, SpatialGlue captured more anatomical details and more accurately resolved spatial domains such as the cortex layers of the brain. Our method also identified cell types like spleen macrophage subsets located at three different zones that were not available in the original data annotations. SpatialGlue scales well with data size and can be used to integrate three modalities. Our spatial multi-omics analysis tool combines the information from complementary omics modalities to obtain a holistic view of cellular and tissue properties.

Delivery of CRISPR/Cas9 system by AAV as vectors for gene therapy.

The adeno-associated virus (AAV) is a defective single-stranded DNA virus with the simplest structure reported to date. It constitutes a capsid protein and single-stranded DNA. With its high transduction efficiency, low immunogenicity, and tissue specificity, it is the most widely used and promising gene therapy vector. The clustered regularly interspaced short palindromic sequence (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing system is an emerging technology that utilizes cas9 nuclease to specifically recognize and cleave target genes under the guidance of small guide RNA and realizes gene editing through homologous directional repair and non-homologous recombination repair. In recent years, an increasing number of animal experiments and clinical studies have revealed the great potential of AAV as a vector to deliver the CRISPR/cas9 system for treating genetic diseases and viral infections. However, the immunogenicity, toxicity, low transmission efficiency in brain and ear tissues, packaging size limitations of AAV, and immunogenicity and off-target effects of Cas9 protein pose several clinical challenges. This research reviews the role, challenges, and countermeasures of the AAV-CRISPR/cas9 system in gene therapy.

Comparative transcriptomic analysis revealed important processes underlying the static magnetic field effects on Arabidopsis.

Static magnetic field (SMF) plays important roles in various biological processes of many organisms including plants, though the molecular mechanism remains largely unclear. Here in this study, we evaluated different magnetic setups to test their effects on growth and development on Arabidopsis (Arabidopsis thaliana), and discovered that plant growth was significantly enhanced by inhomogeneous SMF generated by a regular triangular prism magnet perpendicular to the direction of gravity. Comparative transcriptomic analysis revealed that auxin synthesis and signal transduction genes were upregulated by SMF exposure. SMF also facilitated plants to maintain the iron homeostasis. The expression of iron metabolism-related genes was downregulated by SMF, however, the iron content in plant tissues remains relatively unchanged. Furthermore, SMF exposure also helped the plants to reduce ROS level and synergistically maintain the oxidant balance by enhanced activity of antioxidant enzymes and accumulation of nicotinamide. Taken together, our data suggested that SMF is involved in regulating the growth and development of Arabidopsis thaliana through maintaining iron homeostasis and balancing oxidative stress, which could be beneficial for plant survival and growth. The work presented here would extend our understanding of the mechanism and the regulatory network of how magnetic field affects the plant growth, which would provide insights into the development of novel plant synthetic biology technologies to engineer stress-resistant and high-yielding crops.

Tunable metasurfaces for implementing terahertz controllable NOT logic gate functions.

Compared with traditional electrical logic gates, optical or terahertz (THz) computing logic gates have faster computing speeds and lower power consumption, and can better meet the huge data computing needs. However, there are limitations inherent in existing optical logic gates, such as single input/output channels and susceptibility to interference. Here, we proposed a new approach utilizing polarization-sensitive graphene-vanadium dioxide metasurface THz logic gates. Benefitting from two actively tunable materials, the proposed controlled-NOT logic gate(CNOT LG) enables versatile functionality through a dual-parameter control system. This system allows for the realization of multiple output states under diverse polarized illuminating conditions, aligning with the expected input-output logic relationship of the CNOT LG. Furthermore, to demonstrate the robustness of the designed THz CNOT LG metasurface, we designed an imaging array harnessing the dynamic control capabilities of tunable meta-atoms, facilitating clear near-field imaging. This research is promising for advancing CNOT LG applications in the THz spectrum. It has potential applications in telecommunications, sensing, and imaging.

Impact of foot progression angle on spatiotemporal and plantar loading pattern in intoeing children during gait.

Intoeing in children is a common parental concern, but our understanding of the impact of foot progression angle (FPA) in these children leaves remains limited. This study examines the relationship between FPA and plantar loading pattern, as well as gait symmetry in children with intoeing. The sample included 30 children with intoeing caused by internal tibial torsion, uniformly divided into three groups: unilateral intoeing, bilateral mild intoeing, and bilateral mild-moderate intoeing. The relationship between FPA and plantar loading pattern, and gait symmetry within and among groups were assessed using dynamic pedobarographic and spatiotemporal data. Results indicated a significant correlation between FPA and peak pressure, maximum force, and plantar impulse in the medial and central forefoot, and also the medial and lateral heel zones for both bilateral intoeing groups. Significant differences were observed only in subdivided stance phase, including loading response, single support, and pre-swing phases, between the unilateral intoeing and bilateral mild intoeing groups. These findings suggest that FPA significantly affects the forefoot and heel zones, potentially increasing the load on the support structures and leading to transverse arch deformation. While children with intoeing demonstrate a dynamic self-adjustment capability to maintain gait symmetry, this ability begins to falter as intoeing becomes more pronounced.

A Novel High-Speed Split-Gate Trench Carrier-Stored Trench-Gate Bipolar Transistor with Enhanced Short-Circuit Roughness.

A novel high-speed and process-compatible carrier-stored trench-gate bipolar transistor (CSTBT) combined with split-gate technology is proposed in this paper. The device features a split polysilicon electrode in the trench, where the left portion is equipotential with the cathode. This design mitigates the impact of the anode on the trench gate, resulting in a reduction in the gate-collector capacitance (CGC) to improve the dynamic characteristics. On the left side of the device cell, the P-layer, the carrier-stored (CS) layer and the P-body are formed from the bottom up by ion implantation and annealing. The P-layer beneath the trench bottom can decrease the electric field at the bottom of the trench, thereby improving breakdown voltage (BV) performance. Simultaneously, the highly doped CS layer strengthens the hole-accumulation effect at the cathode. Moreover, the PNP doping layers on the left form a self-biased pMOS. In a short-circuit state, the self-biased pMOS turns on at a certain collector voltage, causing the potential of the CS-layer to be clamped by the hole channel. Consequently, the short-circuit current no longer increases with the collector voltage. The simulation results reveal significant improvements in comparison with the conventional CSTBT under the same on-state voltage (1.48 V for 100 A/cm2). Specifically, the turn-off time (toff) and turn-off loss (Eoff) are reduced by 38.4% and 41.8%, respectively. The short-circuit current is decreased by 50%, while the short-circuit time of the device is increased by 2.46 times.

Alleviating Pyroptosis of Intestinal Epithelial Cells to Restore Mucosal Integrity in Ulcerative Colitis by Targeting Delivery of 4-Octyl-Itaconate.

Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting pyroptosis, was encapsulated by butyrate-modified liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.

Correctable Landmark Discovery Via Large Models for Vision-Language Navigation.

Vision-Language Navigation (VLN) requires the agent to follow language instructions to reach a target position. A key factor for successful navigation is to align the landmarks implied in the instruction with diverse visual observations. However, previous VLN agents fail to perform accurate modality alignment especially in unexplored scenes, since they learn from limited navigation data and lack sufficient open-world alignment knowledge. In this work, we propose a new VLN paradigm, called COrrectable LaNdmark DiScOvery via Large ModEls (CONSOLE). In CONSOLE, we cast VLN as an open-world sequential landmark discovery problem, by introducing a novel correctable landmark discovery scheme based on two large models ChatGPT and CLIP. Specifically, we use ChatGPT to provide rich open-world landmark cooccurrence commonsense, and conduct CLIP-driven landmark discovery based on these commonsense priors. To mitigate the noise in the priors due to the lack of visual constraints, we introduce a learnable cooccurrence scoring module, which corrects the importance of each cooccurrence according to actual observations for accurate landmark discovery. We further design an observation enhancement strategy for an elegant combination of our framework with different VLN agents, where we utilize the corrected landmark features to obtain enhanced observation features for action decision. Extensive experimental results on multiple popular VLN benchmarks (R2R, REVERIE, R4R, RxR) show the significant superiority of CONSOLE over strong baselines. Especially, our CONSOLE establishes the new state-of-the-art results on R2R and R4R in unseen scenarios.

Characterization of the Apoptotic and Antimicrobial Activities of Two Initiator Caspases of Sea Cucumber Apostichopus japonicus.

Caspase (CASP) is a protease family that plays a vital role in apoptosis, development, and immune response. Herein, we reported the identification and characterization of two CASPs, AjCASPX1 and AjCASPX2, from the sea cucumber Apostichopus japonicus, an important aquaculture species. AjCASPX1/2 share similar domain organizations with the vertebrate initiator caspases CASP2/9, including the CARD domain and the p20/p10 subunits with conserved functional motifs. However, compared with human CASP2/9, AjCASPX1/2 possess unique structural features in the linker region between p20 and p10. AjCASPX1, but not AjCASPX2, induced marked apoptosis of human cells by activating CASP3/7. The recombinant proteins of AjCASPX2 and the CARD domain of AjCASPX2 were able to bind to a wide range of bacteria, as well as bacterial cell wall components, and inhibit bacterial growth. AjCASPX1, when expressed in Escherichia coli, was able to kill the host bacteria. Under normal conditions, AjCASPX1 and AjCASPX2 expressions were most abundant in sea cucumber muscle and coelomocytes, respectively. After bacterial infection, both AjCASPX1 and AjCASPX2 expressions were significantly upregulated in sea cucumber tissues and cells. Together, these results indicated that AjCASPX1 and AjCASPX2 were initiator caspases with antimicrobial activity and likely functioned in apoptosis and immune defense against pathogen infection.

Preparation and characterization of a polyurethane-based sponge wound dressing with a superhydrophobic layer and an antimicrobial adherent hydrogel layer.

Bacterial infection poses a significant impediment in wound healing, necessitating the development of dressings with intrinsic antimicrobial properties. In this study, a multilayered wound dressing (STPU@MTAI2/AM1) was reported, comprising a surface-superhydrophobic treated polyurethane (STPU) sponge scaffold coupled with an antimicrobial hydrogel. A superhydrophobic protective outer layer was established on the hydrophilic PU sponge through the application of fluorinated zinc oxide nanoparticles (F-ZnO NPs), thereby resistance to environmental contamination and bacterial invasion. The adhesive and antimicrobial inner layer was an attached hydrogel (MTAI2/AM1) synthesized through the copolymerization of N-[2-(methacryloyloxy)ethyl]-N, N, N-trimethylammonium iodide and acrylamide, exhibits potent adherence to dermal surfaces and broad-spectrum antimicrobial actions against resilient bacterial strains and biofilm formation. STPU@MTAI2/AM1 maintained breathability and flexibility, ensuring comfort and conformity to the wound site. Biocompatibility of the multilayered dressing was demonstrated through hemocompatibility and cytocompatibility studies. The multilayered wound dressing has demonstrated the ability to promote wound healing when addressing MRSA-infected wounds. The hydrogel layer demonstrates no secondary damage when peeled off compared to commercial polyurethane sponge dressing. The STPU@MTAI2/AM1-treated wounds were nearly completely healed by day 14, with an average wound area of 12.2 ± 4.3 %, significantly lower than other groups. Furthermore, the expression of CD31 was significantly higher in the STPU@MTAI2/AM1 group compared to other groups, promoting angiogenesis in the wound and thereby contributing to wound healing. Therefore, the prepared multilayered wound dressing presents a promising therapeutic candidate for the management of infected wounds. STATEMENT OF SIGNIFICANCE: Healing of chronic wounds requires avoidance of biofouling and bacterial infection. However developing a wound dressing which is both anti-biofouling and antimicrobial is a challenge. A multilayered wound dressing with multifunction was developed. Its outer layer was designed to be superhydrophobic and thus anti-biofouling, and its inner layer was broad-spectrum antimicrobial and could inhibit biofilm formation. The multilayered wound dressing with adhesive property could easily be removed from the wound surface preventing the cause of secondary damage. The multilayered wound dressing has demonstrated good abilities to promote MRSA-infected wound healing and presents a viable treatment for MRSA-infected wound.

Evaluation of the antitumor effect of neoantigen peptide vaccines derived from the translatome of lung cancer.

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.

Health insurance fraud detection based on multi-channel heterogeneous graph structure learning.

Health insurance fraud is becoming more common and impacting the fairness and sustainability of the health insurance system. Traditional health insurance fraud detection primarily relies on recognizing established data patterns. However, with the ever-expanding and complex nature of health insurance data, it is difficult for these traditional methods to effectively capture evolving fraudulent activity and tactics and keep pace with the constant improvements and innovations of fraudsters. As a result, there is an urgent need for more accurate and flexible analytics to detect potential fraud. To address this, the Multi-channel Heterogeneous Graph Structured Learning-based health insurance fraud detection method (MHGSL) was proposed. MHGSL constructs a graph of health insurance data from various entities, such as patients, departments, and medicines, and employs graph structure learning to extract topological structure, features, and semantic information to construct multiple graphs that reflect the diversity and complexity of the data. We utilize deep learning methods such as heterogeneous graph neural networks and graph convolutional neural networks to combine multi-channel information transfer and feature fusion to detect anomalies in health insurance data. The results of extensive experiments on real health insurance data demonstrate that MHGSL achieves a high level of accuracy in detecting potential fraud, which is better than existing methods, and is able to quickly and accurately identify patients with fraudulent behaviors to avoid loss of health insurance funds. Experiments have shown that multi-channel heterogeneous graph structure learning in MHGSL can be very helpful for health insurance fraud detection. It provides a promising solution for detecting health insurance fraud and improving the fairness and sustainability of the health insurance system. Subsequent research on fraud detection methods can consider semantic information between patients and different types of entities.

Spatially selective p-type doping for constructing lateral WS2 p-n homojunction via low-energy nitrogen ion implantation.

The construction of lateral p-n junctions is very important and challenging in two-dimensional (2D) semiconductor manufacturing process. Previous researches have demonstrated that vertical p-n junction can be prepared simply by vertical stacking of 2D materials. However, interface pollution and large area scalability are challenges that are difficult to overcome with vertical stacking technology. Constructing 2D lateral p-n homojunction is an effective strategy to address these issues. Spatially selective p-type doping of 2D semiconductors is expected to construct lateral p-n homojunction. In this work, we have developed a low-energy ion implantation system that reduces the implanted energy to 300 eV. Low-energy implantation can form a shallow implantation depth, which is more suitable for modulating the electrical and optical properties of 2D materials. Hence, we utilize low-energy ion implantation to directly dope nitrogen ions into few-layer WS2 and successfully realize a precise regulation for WS2 with its conductivity type transforming from n-type to bipolar or even p-type conduction. Furthermore, the universality of this method is demonstrated by extending it to other 2D semiconductors, including WSe2, SnS2 and MoS2. Based on this method, a lateral WS2 p-n homojunction is fabricated, which exhibits significant rectification characteristics. A photodetector based on p-n junction with photovoltaic effect is also prepared, and the open circuit voltage can reach to 0.39 V. This work provides an effective way for controllable doping of 2D semiconductors.

Highly Stable 72-Nuclearity Nanocages for Efficient Synthesis of Aryl Nitriles via Ni/Cu Synergistic Catalysis.

Seeking noble-metal-free catalysts for efficient synthesis of aryl nitriles under mild conditions poses a significant challenge due to the use of hypertoxic cyanides or high-pressure/temperature NH3/O2 in conventional synthesis processes. Herein, we developed a novel framework 1 assembled by [Ni72] nanocages with excellent solvents/pH stability. To investigate the structure-activity relationship of catalytic performance, several isostructural MOFs with different molar ratios of Ni/Cu by doping Cu2+ into framework 1 (Ni0.59Cu0.41 (2), Ni0.81Cu0.19 (3), Ni0.88Cu0.12 (4), and Ni0.92Cu0.08 (5)) were prepared. Catalytic studies revealed that catalyst 3 exhibited remarkable performance in the synthesis of aryl nitriles, utilizing a formamide alternative to hypertoxic NaCN/KCN. Notably, catalyst 3 achieved an excellent TOF value of 9.8 h-1. Furthermore, catalyst 3 demonstrated its applicability in a gram-scale experiment and maintained its catalytic performance even after six recycling cycles, owing to its high stability resulting from significant electrostatic and orbital interactions between the Ni center and ligands as well as a large SOMO-LUMO energy gap supported by DFT calculations. Control experiments and DFT calculations further revealed that the excellent catalytic performance of catalyst 3 originated from the synergistic effect of Ni/Cu. Importantly, this work not only provides a highly feasible method to construct highly stable MOFs containing multinuclear nanocages with exceptional catalytic performance but also represents the first example of a heterogeneous catalyst for the synthesis of aryl nitriles using formamide as the cyanide source.

Advanced drive laser system for a high-brightness continuous-wave photocathode electron gun.

In order to enhance the performance of a continuous-wave photocathode electron gun at Peking University, and to achieve electron beams with higher current and brightness, a multifunctional drive laser system named PULSE (Peking University drive Laser System for high-brightness Electron source) has been developed. This innovative system is capable of delivering an average output power of 120 W infrared laser pulse at 81.25 MHz, as well as approximately 13.8 W of green power with reliable stability. The utilization of two stages of photonic crystal fibers plays a crucial role in achieving this output. Additionally, the incorporation of two acousto-optic modulators enables the selection of macro-pulses with varying repetition frequencies and duty cycles, which is essential for effective electron beam diagnosis. Furthermore, the system employs a series of birefringent crystals for temporal pulse shaping, allowing for stacking Gaussian pulses into multiple types of distribution. Overall, the optical schematic and operating performance of PULSE are detailed in this paper.

Tuning the electronic properties and band offset of h-BN/diamond mixed-dimensional heterostructure by biaxial strain.

The h-BN/diamond mix-dimensional heterostructure has broad application prospects in the fields of optoelectronic devices and power electronic devices. In this paper, the electronic properties and band offsets of hexagonal boron nitride (h-BN)/(H, O, F, OH)-diamond (111) heterostructures were studied by first-principles calculations under biaxial strain. The results show that different terminals could significantly affect the interface binding energy and charge transfer of h-BN/diamond heterostructure. All heterostructures exhibited semiconductor properties. The h-BN/(H, F)-diamond systems were indirect bandgap, while h-BN/(O, OH)-diamond systems were direct bandgap. In addition, the four systems all formed type-II heterostructures, among which h-BN/H-diamond had the largest band offset, indicating that the system was more conducive to the separation of electrons and holes. Under biaxial strain the bandgap values of the h-BN/H-diamond system decreased, and the band type occurred direct-indirect transition. The bandgap of h-BN/(O, F, OH)-diamond system increased linearly in whole range, and the band type only transformed under large strain. On the other hand, biaxial strain could significantly change the band offset of h-BN/diamond heterostructure and promote the application of this heterostructure in different fields. Our work provides theoretical guidance for the regulation of the electrical properties of h-BN/diamond heterostructures by biaxial strain.

Cellulose-based materials in environmental protection: A scientometric and visual analysis review.

As sustainable materials, cellulose-based materials have attracted significant attention in the field of environmental protection, resulting in the publication of numerous academic papers. However, there is a scarcity of literature that involving scientometric analysis within this specific domain. This review aims to address this gap and highlight recent research in this field by utilizing scientometric analysis and a historical review. As a result, 21 highly cited articles and 10 mostly productive journals were selected out. The scientometric analysis reveals that recent studies were objectively clustered into five interconnected main themes: extraction of cellulose from raw materials and its degradation, adsorption of pollutants using cellulose-based materials, cellulose-acetate-based membrane materials, nanocellulose-based materials, and other cellulose-based materials such as carboxymethyl cellulose and bacterial cellulose for environmental protection. Analyzing the distribution of author keywords and thoroughly examining relevant literature, the research focuses within these five themes were summarized. In the future, the development of eco-friendly and cost-effective methods for extracting and preparing cellulose and its derivatives, particularly nanocellulose-based materials, remains an enduring pursuit. Additionally, machine learning techniques holds promise for the advancement and application of cellulose-based materials. Furthermore, there is potential to expand the research and application scope of cellulose-based materials for environmental protection.

Preventing CXCL12 elevation helps to reduce acute exacerbation of COPD in individuals co-existing type-2 diabetes: A bioinformatics and clinical pharmacology study.

AIMS: To investigate the immunology shared mechanisms underlying chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) and examine the impact of anti-diabetic drugs on acute exacerbation of COPD (AECOPD). METHODS: We analyzed GSE76925, GSE76894, GSE37768, and GSE25724 to identify differentially expressed genes. Hub-genes were identified through protein-protein interaction network analysis and evaluated by the receiver operating characteristic curve. CXCL12 emerged as a robust biomarker, and its correlation with lung function and CD8+ T cells were further quantified and validated. The activated signaling pathways were inferred through Gene set enrichment analysis (GSEA). The retrospective clinical analysis was executed to identify the influence of dipeptidyl peptidase-4 inhibitors (DPP-4i) on CXCL12 and evaluate the drug's efficacy in AECOPD. RESULTS: The significant up-regulation of CXCL12 expression in patients with two diseases were revealed. CXCL12 exhibited a negative correlation with pulmonary function (r = -0.551, p < 0.05). Consistent with analysis in GSE76925 and GSE76894, the positive correlation between the proportion of CD8+ T cells was demonstrated(r=0.469, p<0.05). GSEA identified "cytokines interaction" as an activated signaling pathway, and the clinical study revealed the correlation between CXCL12 and IL-6 (r=0.668, p<0.05). In patients with COPD and T2DM, DDP-4i treatment exhibited significantly higher serum CXCL12, compared to GLP-1RA. Analysis of 187 COPD patients with T2DM indicated that the DPP-4i group had a higher frequency of AECOPD compared to the GLP-1RA group (OR 1.287, 95%CI [1.018-2.136]). CONCLUSIONS: CXCL12 may represent a therapeutic target for COPD and T2DM. GLP-1RA treatment may be associated with lower CXCL12 levels and a lower risk of AECOPD compared to DPP-4i treatment. CLINICAL TRIAL REGISTRATION: China Clinical Trial Registration Center（ChiCTR2200055611）.