An arabinan from Citrus grandis fruits alleviates ischemia/reperfusion-induced myocardial cell apoptosis via the Nrf2/Keap1 and IRE1/GRP78 signaling pathways.

Citrus grandis fruit is a famous traditional Chinese medicine with various bioactivities, including cardioprotective effects. Polysaccharides are one of the key active ingredients responsible for its cardioprotective effects. This study aimed to investigate the structure and cardioprotective effect of a homogeneous polysaccharide from C. grandis fruit (CGP80-1) and explore its mechanism against myocardial ischemia-reperfusion (MI/R) injury. Structure analysis showed that CGP80-1 (11,917 Da) is an arabinan with compact coil chain conformation, containing →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, and →2,3,5)-α-L-Araf-(1→ as the backbone, as well as →5)-α-L-Araf-(1→ and t-α-L-Araf as side-chains substituted at the C2 and C3 positions. Pharmacological experiments showed that pre-treatment with CGP80-1 could effectively alleviate MI/R injury by improving endogenous antioxidant enzymes and cardiac enzymes, reducing reactive oxygen species levels, and regulating apoptosis-related proteins such as caspase-3, Bax, and Bcl-2. The protective effects were correlated with the Nrf2/Keap1 and IRE1/GRP78 signaling pathways. Further analysis of structure-activity relationships revealed that the myocardial protection effects of CGP80-1 might be attributed to its appropriate molecular weight, high arabinose content, and unique compact coil chain conformation. Overall, our results provide insight into the chemical structure of CGP80-1 and its mechanism of action, suggesting that CGP80-1 could be a candidate drug for myocardial protection.

Structurally Colored Photonic Crystal Biomimetic Microstructures for Daytime Radiative Cooling.

Daytime radiative cooling offers a novel solution to the energy crisis, enabling green and efficient thermal management in space. High reflectance in the solar spectrum is essential for passive radiative cooling, rendering dye coloring and similar methods unsuitable for colored coolers. This paper presents a structurally colored photonic crystal biomimetic microstructured radiative cooler. Inspired by natural biological systems, this cooler features a dual-layered microtruncated-cone array structure on the surface and bottom membrane layers. The silver reflector and 3D micrograting surface structure produce continuous iridescent colors through multiple interference effects. Optimized lithographic process enable the fabrication of the ordered dual-layer surface microstructure arrays with precise angular combinations. The dual-layered microtruncated-cone introduces a gradient refractive index, reducing impedance mismatch at the interface. As a result, the radiative cooler achieves high solar spectral reflectance (0.95) and high mid-infrared emissivity (0.95). Notably, the net theoretical cooling power and the subambient temperature drop are 106.9 W m-2 and 7.4 °C, respectively, at an ambient temperature of 40 °C, with a measured average temperature reduction of 6.1 °C under direct sunlight. This performance matches that of advanced radiative coolers, striking a balance between aesthetics and radiative cooling capability.

Mediating role of accelerated aging in the association between depression and mortality risk: findings from NHANES.

OBJECTIVE: To investigate the association between depression, accelerated biological aging, and mortality risk, and to assess whether accelerated aging mediates the relationship between major depression and mortality risk. METHODS: A prospective cohort of 12,761 participants aged 20 years or older from the 2005-2010 cycle of the National Health and Nutrition Examination Survey (NHANES) was analyzed. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores of ≥ 10 indicating major depression. Accelerated biological aging was measured using phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models and subgroup analyses were used to examine the association between depression and accelerated aging, while weighted multivariable Cox proportional hazards regression models and subgroup analyses assessed the impact of major depression on mortality risk. Mediation analysis was performed to assess whether PhenoAgeAccel mediated the relationship between major depression and mortality outcomes. RESULTS: Among the 12,761 adults, the weighted mean age was 46.6 years, with 48.8% being male, and 6.9% experiencing major depression. The results showed a positive association between major depression and PhenoAgeAccel (ß: 0.61, 95% CI: 0.06-1.16). Over a median follow-up duration of 11.3 years (interquartile range: 9.9-13.1), major depression was associated with increased all-cause mortality (HR: 1.35, 95% CI: 1.13-1.62) and cardiovascular mortality (HR: 1.73, 95% CI: 1.18-2.54). However, the relationship with cancer mortality was not statistically significant after full adjustment for confounding factors. The mediation analysis further revealed that PhenoAgeAccel accounted for 10.32% and 5.12% of the associations between major depression and all-cause mortality, and cardiovascular mortality, respectively. CONCLUSION: Depression is associated with accelerated aging and contributes to increased all-cause and cardiovascular mortality. Accelerated aging partially mediates the association between major depression and mortality risk. Our findings highlight the urgent need to incorporate mental health care into public health strategies to delay population aging and reduce mortality risk.

Microbial inoculants using spent mushroom substrates as carriers improve soil multifunctionality and plant growth by changing soil microbial community structure.

Peat is typically used as a carrier for microbial inoculants; however, due to its non-renewable nature alternatives need to be identified as reliable and renewable carriers for mineral-solubilizing inoculants. In pot experiments, solid microbial inoculants were comprised of peat (P), biochar (BC), and spent mushroom substrates (SMS) using Medicago sativa L. as experimental materials, and the purpose of this study is to assess the effect of solid microbial inoculants on soil multifunctionality and plant growth. The results revealed that the SMS microbial inoculant had the greatest positive impact on plant biomass and significantly stimulated soil multifunctionality which is typically managed or assessed based on various soil functions or processes that are crucial for sustaining productivity, in contrast to the peat microbial inoculant, particularly at a supply level of 100 g/pot. There was no significant correlation between soil multifunctionality and bacterial/fungal microbial diversity. However, according to the co-occurrence network of bacteria and fungi, soil multifunctionality was intimately correlated with the biodiversity of the main ecological clusters (modules) of bacteria and fungi, rather than to the entire soil microbial community structure. The keystone species of module hubs and connectors play critical roles in maintaining the stability of ecological clusters of microbial co-occurrence networks and linkages between ecological clusters. Soil pH is a major predictor of changes in plant biomass, and leads to changes therein by affecting the major ecological clusters of bacterial and fungal co-occurrence networks. These results suggested that SMS may serve as a good alternative to peat as a carrier of mineral-solubilizing microorganisms to maintain soil multifunctionality and promote plant growth.

Gut bacteria facilitate leaf beetles in adapting to dietary specialization by enhancing larval fitness.

Dietary specialization between insect stages can reduce intraspecific food competition. The involvement of gut bacteria and the mechanisms underlying this phenomenon received limited attention. Plagiodera versicolora is a pest harming Salicaceae trees. Here, we confirmed dietary specialization in P. versicolora, wherein adults prefer new leaves, while larvae predominantly consume mature leaves when both types are available. We demonstrated the larval preference for mature leaves confers ecological advantages by promoting growth, development and immunity and this advantage is contingent upon the presence of gut bacteria. Gut microbiota in larvae revealed a significant enrichment of Pantoea when feeding new leaves, with P. anthophila exhibiting the most pronounced inhibitory effect on larval development. Further exploration identified specific metabolites, such as Tyrosyl-valine, with higher content in new leaves, which serve as substrates for the entomopathogenic gut bacterium to facilitate its proliferation. This study provides a fresh perspective on the ecological role of gut bacteria.

Divergent associations of inflammatory markers with bone turnover markers in elderly patients with osteoporotic fractures.

The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient's complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (ß = -1.1788, 95% CI: -1.7230 to -0.6345, P-value < 0.0001) and ß-C-terminal telopeptide of type I collagen (ß-CTX) (ß = -0.0104, 95% CI: -0.0145 to -0.0062, P-value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (ß = -17.4523, 95% CI: -27.7335 to -7.1710, P-value = 0.0009) and ß-CTX (ß = -0.1327, 95% CI: -0.2211 to -0.0443, P-value = 0.0034). However, PLR indicated a positive correlation with P1NP (ß = 0.0326, 95% CI: 0.0007 to 0.0645, P-value = 0.0458) and ß-CTX (ß = 0.0003, 95% CI: 0.0001 to 0.0006, P-value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, ß-CTX. In addition, the stratified analysis validated the result's stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with ß-CTX, whereas PLR demonstrates a positive correlation with ß-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism.

SiPM-based LiDAR with multipulse sequence modulation and multithreshold signal processing.

A light detection and range technology (LiDAR) system that enables rapid ranging under extremely low signal-to-noise ratios (SNRs) during daylight conditions based on a SiPM (silicon photomultiplier) detector is proposed. The system emits a sequence of modulated laser pulses by controlling the semiconductor laser and then processes the SiPM response signals using dynamic multithreshold. The experimental result shows that, under extremely low SNR of daylight, the system achieves a 100% success rate in continuous ranging of a low reflectivity target at 125 m, with a ranging precision of less than 20 cm and a ranging time of less than 10 µs. Our system provides a significant reference value for achieving high-speed, noise-resistant, miniaturized, practical, and low-cost LiDAR based on a SiPM.

Super-resolution fluorescence imaging of PEDOT:PSS films.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a popular conduction polymer and widely used in organic electronics, bioelectronics and printed electronics. It is believed that PEDOT:PSS has a core-shell colloidal structure dispersed in the formulation. However, the size and surface functional groups of the PEDOT:PSS dispersion and films remain to be visualized. Here, we have introduced the concept of aggregation-induced emission (AIE) to super-resolution imaging for designing the cationic probe TPE-4N+ and accomplished the nanoscale optical visualization of PEDOT:PSS films through reversible electrostatic interactions. Information on the PEDOT:PSS size and surface charge has been successfully collected via super-resolution imaging. The full-width at half-maximum (FWHM) of PSS nanoparticles was observed to be approximately 30-40 nm. The super-resolution fluorescence imaging method can also be used to monitor the PEDOT:PSS film after acid treatment. It was observed that PSS chains were washed away when exposed to concentrated sulfuric acid, which explains why concentrated sulfuric acid treatment greatly improves the conductivity of the PEDOT:PSS film. Super-resolution imaging is promising as an effective method for characterizing PEDOT:PSS films.

LnIII/CuI Bimetallic Nanoclusters with Enhanced NIR-II Luminescence.

Coinage-metal clusters with excellent luminescence properties have attracted considerable interest due to their intriguing structures and potential applications. However, achieving strong near-infrared (NIR) luminescence in these clusters is highly challenging. Here, we have successfully synthesized the first LnIII/CuI bimetallic clusters, formulated as [LnCu54O6Cl3(2-MeO-PhC≡C)36] (ClO4)6 (Ln = Yb for YbCu54, Er for ErCu54, and Gd for GdCu54). Single crystal X-ray diffraction showed that the LnCu54 clusters have a three-layered core-shell structure, consisting of (LnO6)@Cu18Cl3@Cu36 units protected by 36 2-MeO-PhC≡C- ligands. Notably, the YbCu54 cluster exhibits significant NIR-II luminescence at 986 nm with the solid quantum efficiency of 33.3%, the highest among Cu clusters with NIR-II emission. This work not only reports the first category of LnIII/CuI clusters but also presents a method to enhance NIR luminescence in coinage-metal clusters through the incorporation of LnIII ions.

Bottom-up construction of chiral metal-peptide assemblies from metal cluster motifs.

The exploration of artificial metal-peptide assemblies (MPAs) is one of the most exciting fields because of their great potential for simulating the dynamics and functionality of natural proteins. However, unfavorable enthalpy changes make forming discrete complexes with large and adaptable cavities from flexible peptide ligands challenging. Here, we present a strategy integrating metal-cluster building blocks and peptides to create chiral metal-peptide assemblies and get a family of enantiopure [R-/S-Ni3L2]n (n = 2, 3, 6) MPAs, including the R-/S-Ni6L4 capsule, the S-Ni9L6 trigonal prism, and the R-/S-Ni18L12 octahedron cage. X-ray crystallography shows MPA formation reactions are highly solvent-condition-dependent, resulting in significant changes in ligand conformation and discrete cavity sizes. Moreover, we demonstrate that a structure transformation from Ni18L12 to Ni9L6 in the presence of benzopyrone molecules depends on the peptide conformational selection in crystallization. This work reveals that a metal-cluster building block approach enables facile bottom-up construction of artificial metal-peptide assemblies.

Ursolic Acid Regulates Immune Balance, Modulates Gut Microbial Metabolism, and Improves Liver Health in Mice.

Ursolic acid (UA) has demonstrated significant immunomodulatory and hepatoprotective effects; however, the underlying mechanisms remain unclear. This study aims to analyze the impact of UA on the gut microbiome, metabolome, and liver transcriptome, investigate UA's role in maintaining gut immune homeostasis and liver health, and evaluate the potential contributions of gut microbes and their metabolites to these beneficial effects. Our findings indicate that UA enhances immune balance in the jejunum, fortifies intestinal barrier function, and promotes overall gut health. UA modulates the intestinal microbiota and its metabolic processes, notably increasing the abundance of beneficial bacteria such as Odoribacter and Parabacteroides, along with their metabolites, including ornithine and lactucin. Additionally, UA inhibits the expression of interleukin-1 receptor 1 (IL1R1) and calcium (Ca2+) voltage-gated channel auxiliary subunit beta 2 (CACNB2) while enhancing the synthesis pathways of retinol and ascorbic acid, thereby exerting a protective influence on liver function. In summary, UA enhances intestinal immune homeostasis and promotes liver health, with these advantageous effects potentially mediated by beneficial bacteria (Odoribacter and Parabacteroides) and their metabolites (ornithine and lactucin).

A Universal Model for Ultrasonic Energy Transmission in Various Media.

This study presents a comprehensive model for ultrasonic energy transfer (UET) using a 33-mode piezoelectric transducer to advance wireless sensor powering in challenging environments. One of the advantages of UET is that it is not stoppable by electromagnetic shielding and can penetrate metal. Existing models focus on feasibility and numerical analysis but lack an effective link between input and output power in different media applications. The proposed model fills this gap by incorporating key factors of link loss, including resonant frequency, impedance matching, acoustic coupling, and boundary conditions, to predict energy transfer efficiency more accurately. The model is validated through numerical simulations and experimental tests in air, metal, and underwater environments. An error analysis has shown that the maximum error between theoretical and experimental responses is 3.11% (air), 27.37% (water), and 1.76% (aluminum). This research provides valuable insights into UET dynamics and offers practical guidelines for developing efficient wireless powering solutions for sensors in difficult-to-access or electromagnetically shielded conditions.

DMF-Bimol: Counting mRNA and Protein Molecules in Single Cells with Digital Microfluidics.

Analyzing single-cell protein and mRNA levels yields invaluable insights into cellular functions and the intricacies of biologically heterogeneous systems. Current joint mRNAs and protein analysis methodologies suffer from relative quantification, low sensitivity, possible background interference, and tedious manual manipulation. Therefore, we propose DMF-Bimol that leverages addressable digital microfluidics to automate digital counting of single-cell mRNA and protein based on proximity ligation assay (PLA) and one-step RT-droplet digital PCR (RT-ddPCR). Through an engineered hydrophilic-hydrophobic interface, DMF-Bimol enables efficient single-cell isolation and lossless protein and nucleic acid processing. The closed droplet reaction system enhances the protein concentration and isolates exogenous contaminants, thereby dramatically improving the efficiency of the PLA reaction. The limit of detection of this approach achieves 3313 protein copies, marking a significant 17-fold enhancement in sensitivity over traditional benchtop PLA. This heightened sensitivity also uncovers a lower correlation between mRNA and protein levels in individual cells (Spearman r = 0.255) than bulk results, reflecting the complex relationship in heterogeneous cells. Using DMF-Bimol, we observed a significant upsurge of CD147 protein in CD138+ myeloma cells but consistent levels of CD147 mRNAs compared with normal leukocytes. This discovery indicates a possible consequence of CD147 oncogenic activation that tends to harness protein translation to bolster tumor cell survival and enhance invasiveness, highlighting the potential of DMF-Bimol in unveiling intricate dynamics in translation processes at the single-cell level.

Revealing the hidden RBP-RNA interactions with RNA modification enzyme-based strategies.

RNA-binding proteins (RBPs) are powerful and versatile regulators in living creatures, playing fundamental roles in organismal development, metabolism, and various diseases by the regulation of gene expression at multiple levels. The requirements of deep research on RBP function have promoted the rapid development of RBP-RNA interplay detection methods. Recently, the detection method of fusing RNA modification enzymes (RME) with RBP of interest has become a hot topic. Here, we reviewed RNA modification enzymes in adenosine deaminases that act on RNA (ADAR), terminal nucleotidyl transferase (TENT), and activation-induced cytosine deaminase/ApoB mRNA editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family, regarding the biological function, biochemical activity, and substrate specificity originated from enzyme selves, their domains and partner proteins. In addition, we discussed the RME activity screening system, and the RME mutations with engineered enzyme activity. Furthermore, we provided a systematic overview of the basic principles, advantages, disadvantages, and applications of the RME-based and cross-linking and immunopurification (CLIP)-based RBP target profiling strategies, including targets of RNA-binding proteins identified by editing (TRIBE), RNA tagging, surveying targets by APOBEC-mediated profiling (STAMP), CLIP-seq, and their derivative technology. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Processing > RNA Editing and Modification.

Mapping the Evolution of Digital Health Research: Bibliometric Overview of Research Hotspots, Trends, and Collaboration of Publications in JMIR (1999-2024).

BACKGROUND: While bibliometric studies of individual journals have been conducted, to the best of our knowledge, bibliometric mapping has not yet been utilized to analyze the literature published by the Journal of Medical Internet Research (JMIR). OBJECTIVE: In celebration of the journal's 25th anniversary, this study aimed to review the entire collection of JMIR publications from 1999 to 2024 and provide a comprehensive overview of the main publication characteristics. METHODS: This study included papers published in JMIR during the 25-year period from 1999 to 2024. The data were analyzed using CiteSpace, VOSviewer, and the "Bibliometrix" package in R. Through descriptive bibliometrics, we examined the dynamics and trend patterns of JMIR literature production and identified the most prolific authors, papers, institutions, and countries. Bibliometric maps were used to visualize the content of published articles and to identify the most prominent research terms and topics, along with their evolution. A bibliometric network map was constructed to determine the hot research topics over the past 25 years. RESULTS: This study revealed positive trends in literature production, with both the total number of publications and the average number of citations increasing over the years. And the global COVID-19 pandemic induced an explosive rise in the number of publications in JMIR. The most productive institutions were predominantly from the United States, which ranked highest in successful publications within the journal. The editor-in-chief of JMIR was identified as a pioneer in this field. The thematic analysis indicated that the most prolific topics aligned with the primary aims and scope of the journal. Currently and in the foreseeable future, the main themes of JMIR include "artificial intelligence," "patient empowerment," and "victimization." CONCLUSIONS: This bibliometric study highlighted significant contributions to digital health by identifying key research trends, themes, influential authors, and collaborations. The findings underscore the necessity to enhance publications from developing countries, improve gender diversity among authors, and expand the range of research topics explored in the journal.

Engineering Escherichia coli via introduction of the isopentenol utilization pathway to effectively produce geranyllinalool.

BACKGROUND: Geranyllinalool, a natural diterpenoid found in plants, has a floral and woody aroma, making it valuable in flavors and fragrances. Currently, its synthesis primarily depends on chemical methods, which are environmentally harmful and economically unsustainable. Microbial synthesis through metabolic engineering has shown potential for producing geranyllinalool. However, achieving efficient synthesis remains challenging owing to the limited availability of terpenoid precursors in microorganisms. Thus, an artificial isopentenol utilization pathway (IUP) was constructed and introduced in Escherichia coli to enhance precursor availability and further improve terpenoid synthesis. RESULTS: We first constructed an artificial IUP in E. coli to enhance the supply of precursor geranylgeranyl diphosphate (GGPP) and then screened geranyllinalool synthases from plants to achieve efficient synthesis of geranyllinalool (274.78 ± 2.48 mg/L). To further improve geranyllinalool synthesis, we optimized various cultivation factors, including carbon source, IPTG concentration, and prenol addition and obtained 447.51 ± 6.92 mg/L of geranyllinalool after 72 h of shaken flask fermentation. Moreover, a scaled-up production in a 5-L fermenter was investigated to give 2.06 g/L of geranyllinalool through fed-batch fermentation. To the best of our knowledge, this is the highest reported titer so far. CONCLUSIONS: Efficient synthesis of geranyllinalool in E. coli can be achieved through a two-step pathway and optimization of culture conditions. The findings of this study provide valuable insights into the production of other terpenoids in E. coli.

Concrete-Inspired Bionic Bone Glue Repairs Osteoporotic Bone Defects by Gluing and Remodeling Aging Macrophages.

Osteoporotic fractures are characterized by abnormal inflammation, deterioration of the bone microenvironment, weakened mechanical properties, and difficulties in osteogenic differentiation. The chronic inflammatory state characterized by aging macrophages leads to delayed or non-healing of the fracture or even the formation of bone defects. The current bottleneck in clinical treatment is to achieve strong fixation of the comminuted bone fragments and effective regulation of the complex microenvironment of aging macrophages. Inspired by cement and gravel in concrete infrastructure, a biomimetic bone glue with poly(lactic-co-glycolic acid) microspheres is developed and levodopa/oxidized chitosan hydrogel stabilized on an organic-inorganic framework of nanohydroxyapatite, named DOPM. DOPM is characterized via morphological and mechanical characterization techniques, in vitro experiments with bone marrow mesenchymal stromal cells, and in vivo experiments with an aged SD rat model exhibiting osteoporotic bone defects. DOPM exhibited excellent adhesion properties, good biocompatibility, and significant osteogenic differentiation. Transcriptomic analysis revealed that DOPM improved the inflammatory microenvironment by inhibiting the NF-κB signaling pathway and promoting aging macrophage polarization toward M2 macrophages, thus significantly accelerating bone defect repair and regeneration. This biomimetic bone glue, which enhances osteointegration and reestablishes the homeostasis of aging macrophages, has potential applications in the treatment of osteoporotic bone defects.

Complex genetic variation in nearly complete human genomes.

Diverse sets of complete human genomes are required to construct a pangenome reference and to understand the extent of complex structural variation. Here, we sequence 65 diverse human genomes and build 130 haplotype-resolved assemblies (130 Mbp median continuity), closing 92% of all previous assembly gaps1,2 and reaching telomere-to-telomere (T2T) status for 39% of the chromosomes. We highlight complete sequence continuity of complex loci, including the major histocompatibility complex (MHC), SMN1/SMN2, NBPF8, and AMY1/AMY2, and fully resolve 1,852 complex structural variants (SVs). In addition, we completely assemble and validate 1,246 human centromeres. We find up to 30-fold variation in α-satellite high-order repeat (HOR) array length and characterize the pattern of mobile element insertions into α-satellite HOR arrays. While most centromeres predict a single site of kinetochore attachment, epigenetic analysis suggests the presence of two hypomethylated regions for 7% of centromeres. Combining our data with the draft pangenome reference1 significantly enhances genotyping accuracy from short-read data, enabling whole-genome inference3 to a median quality value (QV) of 45. Using this approach, 26,115 SVs per sample are detected, substantially increasing the number of SVs now amenable to downstream disease association studies.

The Effect of C-X-C Motif Chemokine Ligand 12 in Colorectal Cancer Associated with Chemoresistance and Radioresistance as Well as Stemness.

Background: We aimed to explore the role of C-X-C motif chemokine ligand 12 (CXCL12) and cytokinecytokine receptor interaction signaling pathway in the radiotherapy and chemotherapy resistance as well as cell stemness in colorectal cancer (CRC). Methods: Bioinformatics analysis was used to identify the differentially expressed mRNAs and signal pathways closely related to differentially expressed mRNAs have also been analyzed in March 2022 at the Jinhua Central Hospital, China. Then, the expression of CXCL12 was detected by qRT-PCR in colorectal cancer cells and testing the effects of transfecting CXCL12 into different CRC-derived cell lines. The effects of CXCL12 on cell proliferation were evaluated by chemosensitivity assay and radiation sensitivity assay. Results: Bioinformatics analysis of DEGs found a total of 2429 differentially expressed genes, THBS3 and CXCL12 genes are two abnormally highly expressed genes in the CRC. KEGG analysis showed the correlative signaling pathway, cytokine-cytokine receptor interaction, which is related to cell stemness. Furthermore, the expression of CXCL12 in CRC cells was detected and an increasing trend was obtained in CRC cells. In addition, the chemosensitivity and radiotherapy tolerance were elevated after transfected with CXCL12. Conclusion: CXCL12 could be a potential promote biomarkers in CRC and also promote the chemosensitivity and radiotherapy tolerance.

Development of a web-based tool for estimating individualized survival curves in glioblastoma using clinical, mRNA, and tumor microenvironment features with fusion techniques.

OBJECTIVE: Glioblastoma (GBM), one of the most common brain tumors, is known for its low survival rates and poor treatment responses. This study aims to create a robust predictive model that integrates multiple feature types, including clinical data, RNA expression, and tumor microenvironment data, using fusion techniques to enhance model performance. METHODS: We obtained data from the SEER database to assess the impact of nine demographic and clinical features on the survival of 58,495 GBM patients and built predictive machine learning models. Additionally, mRNA expression data from 600 GBM patients from TCGA, CGGA, and GEO were analyzed. We used Cox regression and LASSO to create a gene signature, which was compared against 13 published signatures for accuracy. Twenty-one machine learning models were applied to predict survival at multiple time points. Finally, we integrated multiple feature types using fusion techniques and developed a Shiny app to provide survival predictions for GBM patients. RESULTS: Using the SEER database, we constructed machine learning models based on nine clinical variables: age, gender, marital status, race, tumor site, laterality, surgery, chemotherapy, and radiation therapy. The best-performing model achieved AUC values of 0.775, 0.728, 0.692, and 0.683 for predicting survival at 6, 12, 18, and 24 months in the testing cohort. In the merged TCGA, CGGA, and GEO cohorts, we identified 11 genes to develop predictive models. These 11 genes outperformed 13 other published gene signatures in predicting the prognosis of GBM. When incorporating mRNA features, tumor microenvironment features, and clinical variables into the fusion models, the AUC values for predicting survival at 6, 12, 18, and 24 months were 0.641, 0.624, 0.655, and 0.637, respectively. A user-friendly tool for predicting the survival curve of individual GBM patients is available at https://zzubioinfo.shinyapps.io/mlGBM/ . CONCLUSIONS: Our study provides a web-based tool that includes two modules: one for predicting survival curves using only clinical variables, and another that integrates multiple feature types for more comprehensive predictions.