Association between glycemia and multi-vessel lesion in participants undergoing coronary angiography: a cross-sectional study.

Background: This study aims to elucidate the association between glycemia and the occurrence of multi-vessel lesions in participants undergoing coronary angiography. Methods: We analyzed 2,533 patients with coronary artery disease who underwent coronary angiography. Of these, 1,973 patients, identified by the endpoint of multi-vessel lesions, were examined using univariate and multivariate logistic regression analyses to determine the relationship between glycemia levels and multi-vessel lesion occurrence. Results: The analysis included 1,973 participants, among whom 474 patients were identified with coronary multi-vessel lesions. Univariate logistic regression analysis demonstrated a positive correlation between glycemia and the occurrence of coronary multi-vessel lesions (OR 1.04; 95% CI 1.01-1.08; p = 0.02). The adjusted model indicated that for each unit increase in glycemia, the risk of developing coronary multi-vessel lesions increased by 4%, showing a significant correlation (p < 0.05). Subgroup analyses revealed that the impact of glycemia on multi-vessel lesions in patients with PCI varied according to gender, age, and smoking status, with the effect being more pronounced in men, older patients, and smokers. Conclusion: Our findings establish a significant association between glycemia and the incidence of multi-vessel lesions, particularly pronounced in male patients, individuals over 45, and smokers.

Adaptive Decision Spatio-temporal neural ODE for traffic flow forecasting with Multi-Kernel Temporal Dynamic Dilation Convolution.

Traffic flow prediction is crucial for efficient traffic management. It involves predicting vehicle movement patterns to reduce congestion and enhance traffic flow. However, the highly non-linear and complex patterns commonly observed in traffic flow pose significant challenges for this task. Current Graph Neural Network (GNN) models often construct shallow networks, which limits their ability to extract deeper spatio-temporal representations. Neural ordinary differential equations for traffic prediction address over-smoothing but require significant computational resources, leading to inefficiencies, and sometimes deeper networks may lead to poorer predictions for complex traffic information. In this study, we propose an Adaptive Decision spatio-temporal Neural Ordinary Differential Network, which can adaptively determine the number of layers of ODE according to the complexity of traffic information. It can solve the over-smoothing problem better, improving overall efficiency and prediction accuracy. In addition, traditional temporal convolution methods make it difficult to deal with complex and variable traffic time information with a large time span. Therefore, we introduce a multi-kernel temporal dynamic expansive convolution to handle the traffic time information. Multi-kernel temporal dynamic expansive convolution employs a dynamic dilation strategy, dynamically adjusting the network's receptive field across levels, effectively capturing temporal dependencies, and can better adapt to the changing time data of traffic information. Additionally, multi-kernel temporal dynamic expansive convolution integrates multi-scale convolution kernels, enabling the model to learn features across diverse temporal scales. We evaluated our proposed method on several real-world traffic datasets. Experimental results show that our method outperformed state-of-the-art benchmarks.

Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. METHODS: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. RESULTS: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 µg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). CONCLUSION: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

Molecular characterization and expression patterns of MTP genes under heavy metal stress in mustard (Brassica juncea L.).

Members of the Metal Tolerance Protein (MTP) family are critical in mediating the transport and tolerance of divalent metal cations. Despite their significance, the understanding of MTP genes in mustard (Brassica juncea) remains limited, especially regarding their response to heavy metal (HM) stress. In our study, we identified MTP gene sets in Brassica rapa (17 genes), Brassica nigra (18 genes), and B. juncea (33 genes) using the HMMER (Cation_efflux; PF01545) and BLAST analysis. For the 33 BjMTPs, a comprehensive bioinformatics analysis covering the physicochemical properties, phylogenetic relationships, conserved motifs, protein structures, collinearity, spatiotemporal RNA-seq expression, GO enrichment, and expression profiling under six HM stresses (Mn2+, Fe2+, Zn2+, Cd2+, Sb3+, and Pb2+) were carried out. According to the findings of physicochemical characteristics, phylogenetic tree, and collinearity, the allopolyploid B. juncea's MTP genes were inherited from its progenitors, B. rapa and B. nigra, with minimal gene loss during polyploidization. Members of the BjMTP family exhibited conserved motifs, promoter elements, and expression patterns across subgroups, consistent with the seven evolutionary branches (G1, G4-G9, and G12) of the MTPs. Further, spatiotemporal expression profiling under HM stresses successfully identified specific genes and crucial cis-regulatory elements associated with the response of BjMTPs to HM stresses. These findings may contribute to the genetic improvement of B. juncea for enhanced HM tolerance, facilitating the remediation of HM-contaminated areas.

Integrated transcriptomics and metabolomics provides insights into the Nicotiana tabacum response to heat stress.

Heat stress is a prevalent factor that significantly damages crops, especially with the ongoing global warming and increasing frequency of extreme weather events. Tobacco is particularly sensitive to temperature fluctuations, experiencing reduced yield and quality under high temperatures. However, the underlying molecular mechanisms of heat resistance in tobacco remain poorly understood. This study comprehensively analyzed biochemical, transcriptomic, and metabolomic responses to heat stress on the root and shoot of the tobacco cultivar K326 compared to control conditions. Heat stress significantly increased the activities of antioxidant enzymes (CAT, POD, and SOD) and levels of osmotic mediators (soluble sugars, sucrose, and proline) in the shoot. Furthermore, transcriptome analysis identified 13,176 differentially expressed genes (DEGs) in the root (6,129 up-regulated and 7,047 down-regulated) and 12,283 DEGs (6,621 up-regulated and 5,662 down-regulated) in the shoot. The root had 24 enriched KEGG pathways, including phenylpropanoid metabolism, while the shoot had 32 significant pathways, such as galactose metabolism and MAPK signaling. The metabolomic data identified 647 metabolites in the root and 932 in the shoot, with carbohydrates and amino acids being the main categories. The root had 116 differentially abundant metabolites (DAMs) (107 up-regulated and 9 down-regulated), and the shoot contained 256 DAMs (251 up-regulated and 5 down-regulated). Joint transcriptome and metabolome analysis showed that galactose metabolism and starch and sucrose metabolism were co-enriched in both tissues. In contrast, amino sugar and nucleotide sugar metabolism was enriched in the root, and purine metabolism in the shoot. The purine metabolic pathway in the shoot can modulate the expression of MYB transcription factors by influencing ABA synthesis and signaling, thereby controlling the accumulation of HSPs, raffinose, sucrose, and trehalose to enhance heat tolerance. Furthermore, NtMYB78, an MYB transcription factor, enhances tolerance for heat stress in tobacco. This research offers a foundational framework for investigating and implementing heat-resistant genes and metabolic pathways in the root and shoot of tobacco seedlings.

A two-stage maintenance trial of cetuximab-based treatment in RAS and BRAF wild-type unresectable metastatic colorectal cancer: a retrospective real-world study.

Background: To investigate the effectiveness and safety of maintenance regimens based on cetuximab, we conducted a real-world, single-arm, retrospective study at a single center. Methods: In Fujian Medical University Union Hospital, patients with unresectable metastatic colorectal cancer (mCRC) who received cetuximab-based maintenance therapy between December 2020 and December 2021 were included. All patients had RAS and BRAF wild-type. The maintenance regimen consisted of 6-12 cycles of cetuximab plus irinotecan (Phase 1) and cetuximab (Phase 2). Patients could receive reintroduction therapy in case of disease progression during Phase 2. Progression-free survival (PFS), overall survival (OS), and safety data were collected. Results: According to the inclusion and exclusion criteria of the study, a total of 108 subjects who received maintenance therapy were included- 51 experienced disease progression during Phase 1, with PFS (1) of 7.3 months. Among the 52 patients who entered Phase 2, 17 were still in this phase at the end of follow-up, with PFS (2) of 10.1 months. In Phase 2, 35 patients experienced disease progression, of whom 24 received reintroduction therapy, with PFS (3) of 6.7 months. The overall PFS (total) during the maintenance period was 11.9 months, and the OS was 39.2 months. Grade III or higher adverse events were 4.6% during Phase 1 and 0% during Phase 2. Conclusion: Innovative cetuximab-based maintenance therapy showed a trend toward improving the prognosis of mCRC patients with RAS and BRAF wild-type, while the toxic side effects of maintenance therapy were manageable. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2000040940.

Characterising polycyclic aromatic hydrocarbons in road dusts and stormwater in urban environments.

The presence of polycyclic aromatic hydrocarbons (PAHs) pollution on urban road surfaces is one of the major environmental concerns. However, knowledge on the distribution variability of PAHs in road dusts (RDS) and stormwater is limited, which would restrict the further risk evaluation and mitigation implementation of PAHs in road stormwater runoff. This study collected RDS samples and stormwater samples on fourteen urban roads in Shenzhen, China. This study investigated the variation of sixteen PAHs species in RDS and stormwater, and further evaluated the intrinsic and extrinsic factors which influence PAHs accumulation on urban road surfaces. The research outcomes showed significant differences on spatial distribution of PAHs in RDS and in stormwater. The land use types, industrial, commercial and port areas and vehicular volume have a positive relationship with PAHs abundance while dust particle size showed a negative correlation with PAHs abundance. For two phases in stormwater, fluctuation of PAHs with the rainfall duration in total dissolved solid (TDS) was more intensive than in dissolved liquid phase (DLP). This indicated when PAHs attached to RDS enter stormwater, most of PAHs still tend to be on solid particles than in liquid. The study outcomes are expected to contribute to efficient designs of PAHs polluted stormwater mitigation.

Positive selection in cilia-related genes may facilitate deep-sea adaptation of Thermocollonia jamsteci.

Deep-sea hydrothermal vents are characterized by high hydrostatic pressure, hypoxia, darkness and toxic substances. However, how organisms adapt to such extreme marine ecosystems remain poorly understood. We hypothesize that adaptive evolution plays an essential role in generating novelty for evolutionary adaptation to the deep-sea environment because adaptive evolution has been found to be critical for species origin and evolution. In this project, the chromosome-level genome of the deep-sea hydrothermal vent gastropod T. jamsteci was constructed for the first time to examine molecular mechanisms of its adaptation to the deep-sea environment. The genome size was large (2.54 Gb), ranking at the top of all species in the Vetigastropoda subclass, driven primarily by the bursts of transposable elements (TEs). The transposition of TEs may also trigger chromosomal changes including both inter-chromosomal fusions and intra-chromosomal activities involving chromosome inversions, rearrangements and fusions, as revealed by comparing the genomes of T. jamsteci and its closely related shallow-sea species Gibbula magus. Innovative changes including the expansion of the ABC transporter gene family that may facilitate detoxification, duplication of genes related to endocytosis, immunity, apoptosis, and anti-apoptotic domains that may help T. jamsteci fight against microbial pathogens, were identified. Furthermore, comparative analysis identified positive selection signals in a large number of genes including the hypoxia up-regulated protein 1, which is a chaperone that may promote adaptation of the T. jamsteci to hypoxic deepsea environments, hox2, Rx2, Pax6 and cilia-related genes BBS1, BBS2, BBS9 and RFX4. Notably, because of the critical importance of cilia and IFT in development, positive selection in cilia-related genes may play a critical role in facilitating T. jamsteci to adapt to the high-pressure deep-sea ecosystem. Results from this study thus revealed important molecular clues that may facilitate further research on the adaptation of molluscs to deep-sea hydrothermal vents.

Recent Progress on Flexible Self-Powered Tactile Sensing Platforms for Health Monitoring and Robotics.

Over the past decades, tactile sensing technology has made significant advances in the fields of health monitoring and robotics. Compared to conventional sensors, self-powered tactile sensors do not require an external power source to drive, which makes the entire system more flexible and lightweight. Therefore, they are excellent candidates for mimicking the tactile perception functions for wearable health monitoring and ideal electronic skin (e-skin) for intelligent robots. Herein, the working principles, materials, and device fabrication strategies of various self-powered tactile sensing platforms are introduced first. Then their applications in health monitoring and robotics are presented. Finally, the future prospects of self-powered tactile sensing systems are discussed.

Integrated bioinformatics analysis and experimental validation to understand tryptophan metabolism-related genes in hepatocellular carcinoma.

Background: Tryptophan (Trp) metabolism is closely related to tumor immunity, and its disorder can cause an immunosuppressive microenvironment, promoting the occurrence and development of hepatocellular carcinoma (HCC). The aim of this study is to explore and validate the independent prognostic genes in patients suffered from HCC. Methods: The transcriptome data of GSE87630 from GEO database were downloaded to analyze differentially expressed genes (DECs) which were intersected with the gene sets of Trp metabolism from MsigDB database. Univariate/multivariate COX regression was performed to identify the genes with independent prognostic significance. TCGA, GTEx, UALCAN, and GEPIA2 databases were applied to analyze DEGs for prognosis. RNA seq data of HCC from TCGA database were collected for Lasso regression analysis. The ssGSEA algorithm was used to perform the analysis of TCGA data. The effects of the candidate differential gene on HCC cells proliferation and migration were evaluated using EdU immunofluorescence and transwell assays. Results: Trp metabolism-related DECs for HCCs were obtained, including MAOB, CYP1A2, KYNU, CYP2E1, ALDH2, CYP2C18, TDO2, AOX1, CYP3A4 and INMT. Moreover, multivariate COX regression results showed that ALDH2 can serve as an independent prognostic molecule and its transcriptional and translational levels were significantly reduced in the tumor tissues. The low expression of ALDH2 was associated with poor prognosis. Overexpression of ALDH2 dramatically reduced the HCC cells proliferation and migration. Conclusion: ALDH2 is associated with Trp metabolism and its downregulation in HCC has a potential value on prognosis. Overexpression of ALDH2 can reduce the proliferation and migration of HCC cells.

EARLY FLOWERING3-1 represses Grain number, plant height, and heading date7 to promote ABC1 REPRESSOR1 and regulate nitrogen uptake in rice.

The extensive use of nitrogen fertilizer boosts rice (Oryza sativa) production but also harms ecosystems. Therefore, enhancing crop nitrogen use efficiency is crucial. Here, we performed map-based cloning and identified the EARLY FLOWERING3 (ELF3) like protein-encoding gene OsELF3-1, which confers enhanced nitrogen uptake in rice. OsELF3-1 forms a ternary complex (OsEC) with OsELF4s and OsLUX, the putative orthologs of ELF4 and LUX ARRHYTHMO (LUX) in Arabidopsis (Arabidopsis thaliana), respectively. OsEC directly binds to the promoter of Grain number, plant height, and heading date7 (Ghd7) and represses its expression. Ghd7 encodes a transcription factor that has major effects on multiple agronomic traits. Ghd7 is also a transcriptional repressor and directly suppresses the expression of ABC1 REPRESSOR1 (ARE1), a negative regulator of nitrogen use efficiency. Therefore, targeting the OsEC-Ghd7-ARE1 module offers an approach to enhance nitrogen uptake, presenting promising avenues for sustainable agriculture.

In Silico Comparison of Three Different Beam Arrangements for Intensity-Modulated Proton Therapy for Postoperative Whole Pelvic Irradiation of Prostate Cancer.

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT2B) (opposed laterals), three-field (IMPT3B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT4B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT3B and IMPT4B plans, while several rectum objectives were exceeded by IMPT2B plans. IMPT4B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT2B +/- IMPT3B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.

Genetic Strategies and Mechanisms for Improving Ribonucleic Acid Levels of Saccharomyces pastorianus.

Developing microorganisms with a high ribonucleic acid (RNA) content is crucial for the RNA industry. Numerous studies have been conducted to enhance RNA production in yeast cells through genetic engineering, yet precise mechanisms remain elusive. Previously, upregulation of TAL1 or PGM2 and deleting PRS5 or DBP8 individually could increase the RNA content in Saccharomyces pastorianus. In this study, within these genetically modified strains, the intracellular nucleotide levels notably increased following cell fragmentation. Deletion of PRS5 and DBP8 within the strain prompted the upregulation of genes sharing similar functions, consequently augmenting the flow of the gene pathway. Furthermore, the upregulation of genes encoding cell-cycle-dependent protein kinases (CDK) was observed in the G03-△PRS5 strain. The influence of TAL1 and PGM2 on RNA content was attributed to the pentose phosphate pathway (PPP). The RNA content of polygenic recombinant strains, G03-△PRS5+△DBP8 and G03-△PRS5+△DBP8+PGM2, displayed the most significant improvement, increasing by 71.8 and 80.1% when compared to the parental strain. Additionally, the maximum specific growth rate of cells increased in these strains. This study contributes valuable insights into the genetic mechanisms underlying high nucleic acid synthesis in S. pastorianus.

Heparinized self-healing polymer coating with inflammation modulation for blood-contacting biomedical devices.

The current techniques for antithrombotic coating on blood-contacting biomedical materials and devices are usually complex and lack practical feasibility with weak coating stability and low heparin immobilization. Here, a heparinized self-healing polymer coating with inflammation modulation is introduced through thermal-initiated radical copolymerization of methacrylate esterified heparin (MA-heparin) with methyl methacrylate (MMA) and n-butyl acrylate (nBA), followed by the anchoring of reactive oxygen species (ROS)-responsive polyoxalate containing vanillyl alcohol (PVAX) onto the coating through esterification. The aspirin, which is readily dissolved in the solution of MMA and nBA, is encapsulated within the coating after copolymerization. The copolymerization of MA-heparin with MMA and nBA significantly increases the heparin content of the coating, effectively inhibiting thrombosis and rendering the coating self-healing to help maintain long-term stability. ROS-responsive PVAX and aspirin released in a temperature-dependent manner resist acute and chronic inflammation, respectively. The heparinized self-healing and inflammation-modulated polymer coating exhibits the ability to confer long-term stability and hemocompatibility to blood-contacting biomedical materials and devices. STATEMENT OF SIGNIFICANCE: Surface engineering for blood-contacting biomedical devices paves a successful way to reduce thrombotic and inflammatory complications. However, lack of effectiveness, long-term stability and practical feasibility hinders the development and clinical application of existing strategies. Here we design a heparinized self-healing and inflammation-modulated polymer coating, which possesses high heparin level and self-healing capability to maintain long-term stability. The polymer coating is practically feasible to varied substrates and demonstrated to manipulate inflammation and prevent thrombosis both in vitro and in vivo. Our work provides a new method to develop coatings for blood-contacting biomedical materials and devices with long-term stability and hemocompatibility.

Perovskite-Doped Modulated Color-Selective Photosynaptic Transistors for Target Object Recognition.

The processing of multicolor noisy images in visual neuromorphic devices requires selective absorption at specific wavelengths; however, it is difficult to achieve this because the spectral absorption range of the device is affected by the type of material. Surprisingly, the absorption range of perovskite materials can be adjusted by doping. Herein, a CdCl2 co-doped CsPbBr3 nanocrystal-based photosensitive synaptic transistor (PST) is reported. By decreasing the doping concentration, the response of the PST to short-wavelength light is gradually enhanced, and even weak light of 40 µW·cm-2 can be detected. Benefiting from the excellent color selectivity of the PST device, the device array is applied to feature extraction of target blue items and removal of red and green noise, which results in the recognition accuracy of 95% for the noisy MNIST data set. This work provides new ideas for the application of novel transistors integrating sensors and storage computing.

Nondisassembly Repair of Degraded LiFePO4 Cells via Lithium Restoration from the Solid Electrolyte Interphase.

The disposal of degraded batteries will be a severe challenge with the expanding market demand for lithium iron phosphate (LiFePO4 or LFP) batteries. However, due to a lack of economic and technical viability, conventional metal extraction and material regeneration are hindered from practical application. Herein, we propose a nondisassembly repair strategy for degraded cells through a lithium restoration method based on deep discharge, which can elevate the anodic potential to result in the selective oxidative decomposition and thinning of the solid electrolyte interphase (SEI) on the graphite anode. The decomposed SEI acts as a lithium source to compensate for the Li loss and eliminate Li-Fe antisite defects for degraded LFP. Through this design, the repaired pouch cells show improved kinetic characteristics, significant capacity restoration, and an extended lifespan. This proposed repair scheme relying on SEI rejuvenation is of great significance for extending the service life and promoting the secondary use of degraded cells.

Causal diagnostic model and governance strategies to reduce pollution from ship accidents in Chinese waters.

Ship transportation is a primary mode for global trade and cargo transport, yet even minor discrepancies can lead to ship accidents, causing severe secondary environmental pollution. Maritime accidents involve complex and numerous factors. Formal Concept Analysis (FCA) can identify the key contributing factors and their impact levels by eliminating homogenization factors in maritime accidents. This study constructs an innovative FCA model of ship accidents in Chinese waters, utilizing 172 ship accident reports released by the China Maritime Safety Administration. The analysis reveals seven reduced sets and 23 diagnostic rules of ship accidents. Results show that failed ship registration/security inspection, deficient nautical data and instruments, and management issues are the most critical factors. Three accident chains are identified and corresponding mitigation strategies are proposed to reduce potential pollution from ship accidents. These strategies offer significant reference value for preventing ship accidents and reducing their environmental impact in China and globally.

Ti3C2Tx@PLGA/Icaritin microspheres-modified PLGA/ß-TCP scaffolds modulate Icaritin release to enhance bone regeneration through near-infrared response.

Porous poly (lactic-co-glycolic acid)/ß-tricalcium phosphate/Icaritin (PLGA/ß-TCP/ICT, PTI) scaffold is a tissue engineering scaffold based on PLGA/ß-TCP containing Icaritin, the main active ingredient of the Chinese medicine Epimedium. Due to its excellent mechanical properties and osteogenic effect, PTI scaffold has the potential to promote bone defect repair. However, the release of ICT from the scaffolds is difficult to control. In this study, we constructed Ti3C2Tx@PLGA/ICT microspheres (TIM) and evaluated their characterization as well as ICT release under near-infrared (NIR) irradiation. We utilized TIM to modify the PT scaffold and performed biological experiments. First, we cultured rat bone marrow mesenchymal stem cells on the scaffold to assess biocompatibility and osteogenic potential under on-demand NIR irradiation. Subsequently, to evaluate the osteogenic properties of TIM-modified scaffold in vivo, the scaffold was implanted into a femoral condyle defect model. TIM have excellent drug-loading capacity and encapsulation efficiency for ICT, and the incorporation of Ti3C2Tx endows TIM with photothermal conversion capability. Under 0.90 W cm-2 NIR irradiation, the temperature of TIM maintained at 42.0 ± 0.5°C and the release of ICT was accelerated. Furthermore, while retaining its original properties, the TIM-modified scaffold was biocompatible and could promote cell proliferation, osteogenic differentiation, and biomineralization in vitro, as well as the osteogenesis and osseointegration in vivo, and its effect was further enhanced through the modulation of ICT release under NIR irradiation. In summary, TIM-modified scaffold has the potential to be applied in bone defects repairing.

Revealing the mechanism: the influence of Baicalin on M1/M2 and Th1/Th2 imbalances in mycoplasma gallisepticum infection.

Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.

Palbociclib-derived multifunctional molecules for lysosomal targeting and diagnostic-therapeutic integration.

Aim: Lysosomal pH changes are associated with drug resistance, cell growth and invasion of tumors, but effective and specific real-time monitoring of lysosomal pH compounds for cancer therapy is lacking. Materials & methods: Here, based on the covalent linkage of the anticancer drug palbociclib and fluorescent dye fluorescein isothiocyanate (FITC), we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. Results & discussion: Pal-FITC fluoresces is 20-fold stronger than that of FITC and shows a linear response in the pH range of 4.0-8.2 (R2 = 0.9901). Pal-FITC blocks cells in G1 phase via Cyclin D-CDK4/6-Rb. Conclusion: Our study provides new strategies for tumor-targeted imaging and personalized therapy.

Based on the covalent linkage of the anticancer drug and the fluorescent dye, we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. Pal-FITC responded linearly in the pH range of 4.0­8.2. In addition, Pal-FITC was able to effectively treat lung cancer without toxic side effects on normal cells. It has a significant cell cycle blocking phenomenon and blocks G1 phase cells via Cyclin D-CDK4/6-Rb. Our study provides a new strategy for tumor-targeted imaging and personalized therapy.