Unraveling the complex interactions between ozone pollution and agricultural productivity in China's main winter wheat region using an interpretable machine learning framework.

Surface ozone has become a significant atmospheric pollutant in China, exerting a profound impact on crop production and posing a serious threat to food security. Previous studies have extensively explored the physiological mechanisms of ozone damage to plants. However, the effects of ozone interactions with other environmental factors, such as climate change, on agricultural productivity at the regional scale, particularly under natural conditions, remain insufficiently understood. In this study, we employed an interpretable machine learning framework, specifically the eXtreme Gradient Boosting (XGBoost) algorithm enhanced by SHapley Additive exPlanations (SHAP), to investigate the influence of ozone and its interactions with environmental factors on crop production in China's primary winter wheat region. Additionally, a structural equation model was developed to elucidate the mechanisms driving these interactions. Our findings demonstrate that ozone pollution exerts a significant negative effect on winter wheat productivity (r = -0.47, P < 0.001), with productivity losses escalating from -12.28 % to -22.09 % as ozone levels increase. Notably, the impact of ozone is spatially heterogeneous, with western Shandong province identified as a hotspot for ozone-induced damage. Furthermore, our results confirm the complexity of the relationship between ozone pollution and agricultural productivity, which is influenced by multiple interacting environmental factors. Specifically, we found that severe ozone pollution, when combined with high aerosol concentrations or elevated temperatures, significantly exacerbates crop productivity losses, although drought conditions can partially mitigate these adverse effects. Our study highlights the importance of incorporating the interactive effects of air pollution and climate change into future crop models. The comprehensive framework developed in this study, which integrates statistical modeling with explainable machine learning, provides a valuable methodological reference for quantitatively assessing the impact of air pollution on crop productivity at a regional scale.

Dynamic changes in cellular atlases and communication patterns within yak ovaries across diverse reproductive states unveiled by single-cell analysis.

Yaks (Bos grunniens) exhibit exceptional adaptation to the challenging high-altitude environment of the Qinghai-Tibetan plateau, making them the sole bovine species capable of thriving in such exreme conditions. Investigating the cellular and molecular characteristics of yak ovaries across different reproductive states is crucial for gaining insight into their ovarian functions. Herein, the cellular atlases of yak ovaries in different reproductive states were depicted by single-cell RNA-sequencing (scRNA-seq). The cellular atlases of the ovaries were established by identifying specific gene expression patterns of various cell types, including granulosa cells, theca cells, stromal cells, smooth muscle cells, endothelial cells, glial cell, macrophages, natural killer cells, and proliferating cells. The cellular compositions of the ovaries vary among different reproductive states. Furthermore, the granulosa cells comprise six cell subtypes, while theca cells consist of eight cell subtypes. The granulosa cells and theca cells exhibit distinct biological functions throughout different reproductive states. The two cell types were aligned along their respective pseudotime trajectories. Moreover, a cell-to-cell communication network was constructed among distinct cell types within the ovary, spanning the three reproductive states. Notably, during the estrus period, the granulosa cells demonstrated more prominent interactions with other cell types compared to the remaining reproductive states.

Whole-transcriptome sequencing analysis to identify key circRNAs, miRNAs, and mRNAs in the development of yak testes.

BACKGROUND: The Testis is an important reproductive organ in male mammals and the site for spermatogenesis, androgen synthesis, and secretion. Non-coding RNAs (ncRNAs) play an important regulatory role in various biological processes. However, the regulatory role of ncRNAs in the development of yak testes and spermatogenesis remains largely unclear. RESULT: In this study, we compared the expression profiles of circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in yak testicular tissue samples collected at 6 months (Y6M), 18 months (Y18M), and 4 years (Y4Y). Using RNA sequencing (RNA-Seq), we observed a significant difference in the expression patterns of ncRNAs in the samples collected at different testicular development stages. Twenty-two differentially expressed (DE) circRNAs, 69 DE miRNAs, and 64 DE mRNAs were detected in Y6M, Y18M, and Y4Y testicular samples, respectively. The results of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the source genes of DE circRNAs, predicted target genes of DE miRNAs, and DE mRNAs were specifically associated with signaling pathways and GO terms that were related to sperm synthesis, sperm vitality, and testicular development, such as cell cycle, Wnt signaling pathway, MAPK signaling pathway, GnRH signaling pathway, and spermatogenesis. The analysis of the circRNA-miRNA-mRNA network revealed that some DE ncRNAs, including miR-574, miR-449a, CDC42, and CYP11A1, among others, may be involved in testicular spermatogenesis. Concurrently, various circRNA-miRNA interaction pairs were observed. CONCLUSION: Our findings provide a database of circRNAs, miRNAs, and mRNAs expression profiles in testicular tissue of yaks at different developmental stages and a detailed understanding of the regulatory network of ncRNAs in yak testicular development and provide data that can help elucidate the molecular mechanisms underlying yak testicular development.

Study of volatile flavor derived from lipids degeneration in yak Milk based on Semiquantitative Lipidomics.

Milk lipids greatly affect the volatile flavor of milk, and the relationship between lipids and volatile flavor in yak milk was explored in this study. The volatile flavor compounds (VFCs), lipids profile, fatty acids in yak ordinary milk and colostrum were detected with HP/SPME-GC-MS, the semiquantitative lipidomics based on LC-MS/MS, GC-MS, respectively. The VFCs differences in yak milk were closely related to 1-((1 s,3ar,4r,7 s,7as)-4-hydroxy-7-isopropyl-4-methyloctahloctahydro-1h-inden-1-Yl)-ethanone,2,6,6-trimethyl-2,4-cycloheptadien-1-one, pentanal, 2-phenylethyl propionate, octanoic acid methyl ester, diphosphoric acid diisooctyl ester, (Z)-3,4,4-trimethyl-5-oxo-2-hexenoic acid and acetic acid. The volatile flavor in yak milk was well correlated with milk lipids, and TG(4:0_12:3_18:1), TG(6:0_8:0_18:1), TG(4:0_12:3_18:1), TG(12:0_18:2_18:3) and TG(16:0e_18:1_22:5) were the crucial lipid molecules affecting volatile flavor. The degeneration of above lipids by hydrolysis produced some fatty acids and alcohol, then these compounds were further derived into other VFCs especially above crucial 8 molecules. This study provided a theoretical basis for improving the volatile flavor by controlling lipids in yak milk.

Taxonomic revision of Geotrichum and Magnusiomyces, with the descriptions of five new Geotrichum species from China.

The arthroconidial yeast-like species currently classified in the asexual genera Geotrichum and Saprochaete and the sexual genera Dipodascus, Galactomyces and Magnusiomyces are frequently associated with dairy and cosmetics production, fruit rot and human infection. However, the taxonomic system of these fungi has not been updated to accommodate the new nomenclature code adopting the "one fungus, one name" principle. Here, we performed phylogenetic analyses of these yeast-like species based on the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit of the rRNA gene. Two monophyletic groups were recognised from these species. One group contained Dipodascus, Galactomyces, and Geotrichum species and the other Magnusiomyces and Saprochaete species. We thus assigned the species in each group into one genus and selected the genus name Geotrichum for the first group and Magnusiomyces for the second one based on the principle of priority of publication. Five new Geotrichum species were identified from arthroconidial yeast strains recently isolated from various sources in China. The new species are described as Ge. dehoogii sp. nov., Ge. fujianense sp. nov., Ge. maricola sp. nov., Ge. smithiae sp. nov., and Ge. sinensis sp. nov.

TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.

Long-term monitoring dataset of plankton assemblages in western Taiwan coastal water.

Plankton plays important roles in the marine ecosystems as important producers for primary production, major components in the global biogeochemical cycles, and the foundation of the marine food web. Despite their importance, long-term monitoring data about marine plankton are fairly limited, especially in the Asia-Pacific region. We fill this knowledge gap by providing a 29-year long-term monitoring data on the coastal areas of western Taiwan quarterly from 1993 to 2021. This long-term monitoring data can be used to set proper baseline for detecting human-induced impacts on the plankton, as well as modelling future scenarios under global changes.

Spliceosomal GTPase Eftud2 deficiency-triggered ferroptosis leads to Purkinje cell degeneration.

Spliceosomal GTPase elongation factor Tu GTP binding domain containing 2 (EFTUD2) is a causative gene for mandibulofacial dysostosis with microcephaly (MFDM) syndrome comprising cerebellar hypoplasia and motor dysfunction. How EFTUD2 deficiency contributes to these symptoms remains elusive. Here, we demonstrate that specific ablation of Eftud2 in cerebellar Purkinje cells (PCs) in mice results in severe ferroptosis, PC degeneration, dyskinesia, and cerebellar atrophy, which recapitulates phenotypes observed in patients with MFDM. Mechanistically, Eftud2 promotes Scd1 and Gch1 expression, upregulates monounsaturated fatty acid phospholipids, and enhances antioxidant activity, thereby suppressing PC ferroptosis. Importantly, we identified transcription factor Atf4 as a downstream target to regulate anti-ferroptosis effects in PCs in a p53-independent manner. Inhibiting ferroptosis efficiently rescued cerebellar deficits in Eftud2 cKO mice. Our data reveal an important role of Eftud2 in maintaining PC survival, showing that pharmacologically or genetically inhibiting ferroptosis may be a promising therapeutic strategy for EFTUD2 deficiency-induced disorders.

The metabolic activation of and platelet response to vicagrel vary with P-glycoprotein deficiency, rather than P-glycoprotein inhibition, in mice.

This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved.Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions.Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar.P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice.

The Combined Analysis of GC-IMS and GC-MS Reveals the Differences in Volatile Flavor Compounds between Yak and Cattle-Yak Meat.

In order to investigate the composition and differences in volatile organic compounds (VOCs) in yak and cattle-yak meat and determine the key metabolites and metabolic pathways related to flavor formation. In this study, the VOCs and non-volatile metabolites in Longissimus dorsi muscle of two groups of samples were detected and analyzed by gas chromatography-ion migration spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS). The results showed that 31 VOCs were identified by GC-IMS, including 5 alcohols, 5 ketones, 5 esters, 3 aldehydes, 2 furans, 2 hydrocarbons, 1 amine, 1 acid, 1 thiazole, 1 pyrazine, and 5 others. Most of them were alcohols, ketones, esters, and aldehydes. A total of 75 non-volatile metabolites with significant differences were obtained by GC-MS screening, among which amino acid contents such as serine, glycine, phenylalanine, and aspartic acid were significantly up-regulated in cattle-yak, and glutamic acid and tyrosine were significantly up-regulated in yak. The non-volatile differential metabolites in the two groups were significantly enriched in the metabolic pathways of arginine biosynthesis and oxidative phosphorylation. By combining GC-IMS and GC-MS, this study comprehensively and intuitively reflected the differences in VOCs between yak and cattle-yak meat, and clarified the metabolomic reasons for the differences in VOCs, so as to provide a theoretical basis for meat quality improvement.

Species-level understanding of the bacterial community in Daqu based on full-length 16S rRNA gene sequences.

Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.

Biosafety assessments of hexafluoropropylene trimer derivative as a fluorinated cooling fluid for electronics.

The Internet Data Center (IDC) is one of the most important infrastructures in the field of information technology. The cooling system for heat dissipation of IDC is indispensable due to it generates a large amount of heat during its calculation process, which may potentially harm its normal operation. Electronic fluorinated fluids have been widely used in cooling systems of IDC with stable physical and chemical properties. However, the biological toxicity of electronic fluorinated fluids has not been fully evaluated and there is a lack of unified safety standards, which may pose potential risks to the environment and human health. Here, hexafluoropropylene terpolymer (HFPT) as an example has been systematically studied, fully considering the application scenarios of data centers. Also, the emergency effects of fluorinated coolants in mammalian models from the perspectives of inhalation, skin contact, accidental entry into eyes, accidental ingestion, and chronic toxicity, are evaluated. Multiple in vivo experiments have proven that HFPT not only has stable physical and chemical properties, that can maintain the safe operation of IDC, but also has low physiological toxicity to mammals and can provide health benefits to data center staff and the assurance of surrounding environment. This study proves the good biological safety of electronic fluorinated fluids and provides a reference for environmental assessment and risk management of liquid cooling technology in IDC. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00234-3.

Enhancement of silicon vacancy fluorescence intensity in silicon carbide using a dielectric cavity.

Over the past decades, spin qubits in silicon carbide (SiC) have emerged as promising platforms for a wide range of quantum technologies. The fluorescence intensity holds significant importance in the performance of quantum photonics, quantum information process, and sensitivity of quantum sensing. In this work, a dual-layer Au/SiO2 dielectric cavity is employed to enhance the fluorescence intensity of a shallow silicon vacancy ensemble in 4H-SiC. Experimental results demonstrate an effective fourfold augmentation in fluorescence counts at saturating laser power, corroborating our theoretical predictions. Based on this, we further investigate the influence of dielectric cavities on the contrast and linewidth of optically detected magnetic resonance (ODMR). There is a 1.6-fold improvement in magnetic field sensitivity. In spin echo experiments, coherence times remain constant regardless of the thickness of dielectric cavities. These experiments pave the way for broader applications of dielectric cavities in SiC-based quantum technologies.

Comprehensive analysis of differentially expressed mRNAs, circRNAs, and miRNAs and their ceRNA network in the testis of cattle-yak, yak, and cattle.

Cattle-yak is a hybrid offspring resulting from the crossbreeding of yak and cattle, and it exhibits substantial heterosis in production performance. However, male sterility in cattle-yak remains a concern. Reports suggest that noncoding RNAs are involved in the regulation of spermatogenesis. Therefore, in this study, we comprehensively compared testicular transcription profiles among cattle, yak, and cattle-yak. Numerous differentially expressed genes (DEGs), differentially expressed circRNAs (DECs), and differentially expressed miRNAs (DEMs) were identified in the intersection of two comparison groups, namely cattle versus cattle-yak and yak versus cattle-yak, with the number of DEGs, DECs, and DEMs being 4968, 360, and 59, respectively. The DEGs in cattle-yaks, cattle, and yaks were mainly associated with spermatogenesis, male gamete generation, and sexual reproduction. Concurrently, GO and KEGG analyses indicated that DEC host genes and DEM source genes were involved in the regulation of spermatogenesis. The construction of a potential competing endogenous RNA network revealed that some differentially expressed noncoding RNAs may be involved in regulating the expression of genes related to testicular spermatogenesis, including miR-423-5p, miR-449b, miR-34b/c, and miR-15b, as well as previously unreported miR-6123 and miR-1306, along with various miRNA-circRNA interaction pairs. This study serves as a valuable reference for further investigations into the mechanisms underlying male sterility in cattle-yaks.

Genetic diversity, phylogeography, and maternal origin of yak (Bos grunniens).

BACKGROUND: There is no consensus as to the origin of the domestic yak (Bos grunniens). Previous studies on yak mitochondria mainly focused on mitochondrial displacement loop (D-loop), a region with low phylogenetic resolution. Here, we analyzed the entire mitochondrial genomes of 509 yaks to obtain greater phylogenetic resolution and a comprehensive picture of geographical diversity. RESULTS: A total of 278 haplotypes were defined in 509 yaks from 21 yak breeds. Among them, 28 haplotypes were shared by different varieties, and 250 haplotypes were unique to specific varieties. The overall haplotype diversity and nucleotide diversity of yak were 0.979 ± 0.0039 and 0.00237 ± 0.00076, respectively. Phylogenetic tree and network analysis showed that yak had three highly differentiated genetic branches with high support rate. The differentiation time of clades I and II were about 0.4328 Ma, and the differentiation time of clades (I and II) and III were 0.5654 Ma. Yushu yak is shared by all haplogroups. Most (94.70%) of the genetic variation occurred within populations, and only 5.30% of the genetic variation occurred between populations. The classification showed that yaks and wild yaks were first clustered together, and yaks were clustered with American bison as a whole. Altitude had the highest impact on the distribution of yaks. CONCLUSIONS: Yaks have high genetic diversity and yak populations have experienced population expansion and lack obvious phylogeographic structure. During the glacial period, yaks had at least three or more glacial refugia.

Transforming growth factor-ß1-loaded RADA-16 hydrogel scaffold for effective cartilage regeneration.

Cartilage repair remains a major challenge in clinical trials. These current cartilage repair materials can not effectively promote chondrocyte generation, limiting their practical application in cartilage repair. In this work, we develop an implantable scaffold of RADA-16 peptide hydrogel incorporated with TGF-ß1 to provide a microenvironment for stem cell-directed differentiation and chondrocyte adhesion growth. The longest release of growth factor TGF-ß1 release can reach up to 600 h under physiological conditions. TGF-ß1/RADA-16 hydrogel was demonstrated to be a lamellar porous structure. Based on the cell culture with hBMSCs, TGF-ß1/RADA-16 hydrogel showed excellent ability to promote cell proliferation, directed differentiation into chondrocytes, and functional protein secretion. Within 14 days, 80% of hBMSCs were observed to be directed to differentiate into vigorous chondrocytes in the co-culture of TGF-ß1/RADA-16 hydrogels with hBMSCs. Specifically, these newly generated chondrocytes can secrete and accumulate large amounts of collagen II within 28 days, which can effectively promote the formation of cartilage tissue. Finally, the exploration of RADA-16 hydrogel-based scaffolds incorporated with TGF-ß1 bioactive species would further greatly promote the practical clinical trials of cartilage remediation, which might have excellent potential to promote cartilage regeneration in areas of cartilage damage.

Complete characterization of the yak testicular development using accurate full-length transcriptome sequencing.

Alternative splicing is a prevalent phenomenon in testicular tissues. Due to the low assembly accuracy of short-read RNA sequencing technology in analyzing post-transcriptional regulatory events, full-length (FL) transcript sequencing is highly demanded to accurately determine FL splicing variants. In this study, we performed FL transcriptome sequencing of testicular tissues from 0.5, 1.5, 2.5, and 4-year-old yaks and 4-year-old cattle-yaks using Oxford Nanopore Technologies. The obtained sequencing data were predicted to have 47,185 open reading frames (ORFs), including 26,630 complete ORFs, detected 7645 fusion transcripts, 15,355 alternative splicing events, 25,798 simple sequence repeats, 7628 transcription factors, and 35,503 long non-coding RNAs. A total of 40,038 novel transcripts were obtained from the sequencing data, and the proportion was almost close to the number of known transcripts identified. Structural analysis and functional annotation of these novel transcripts resulted in the successful annotation of 9568 transcripts, with the highest and lowest annotation numbers in the Nr and KOG databases, respectively. Weighted gene co-expression network analysis revealed the key regulatory pathways and hub genes at various stages of yak testicular development. Our findings enhance our comprehension of transcriptome complexity, contribute to genome annotation refinement, and provide foundational data for further investigations into male sterility in cattle-yaks.

Long-Term Changes of Urinary Exosomal Peptide Levels After Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational Study.

Background: The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Methods: Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. Results: A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Conclusion: Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. Trial Registration: ClinicalTrials.gov: NCT03488134.

Role of Exercise on Inflammation Cytokines of Neuropathic Pain in Animal Models.

Neuropathic pain (NP) resulting from a lesion or disease of the somatosensory system can lead to loss of function and reduced life quality. Neuroinflammation plays a vital role in the development and maintenance of NP. Exercise as an economical, effective, and nonpharmacological treatment, recommended by clinical practice guidelines, has been proven to alleviate chronic NP. Previous studies have shown that exercise decreases NP by modifying inflammation; however, the exact mechanisms of exercise-mediated NP are unclear. Therefore, from the perspective of neuroinflammation, this review mainly discussed the effects of exercise on inflammatory cytokines in different parts of NP conduction pathways, such as the brain, spinal cord, dorsal root ganglion, sciatic nerve, and blood in rat/mice models. Results suggested that exercise training could modulate neuroinflammation, inhibit astrocyte glial cell proliferation and microglial activation, alter the macrophage phenotype, reduce the expression of proinflammatory cytokines, increase anti-inflammatory cytokine levels, and positively modulate the state of the immune system, thereby relieving NP.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.