Multispectral Thermometry Method Based on Optimisation Ideas.

Multispectral thermometry is based on the law of blackbody radiation and is widely used in engineering practice today. Temperature values can be inferred from radiation intensity and multiple sets of wavelengths. Multispectral thermometry eliminates the requirements for single-spectral and spectral similarity, which are associated with two-colour thermometry. In the process of multispectral temperature inversion, the solution of spectral emissivity and multispectral data processing can be seen as the keys to accurate thermometry. At present, spectral emissivity is most commonly estimated using assumption models. When an assumption model closely matches an actual situation, the inversion of the temperature and the accuracy of spectral emissivity are both very high; however, when the two are not closely matched, the inversion result is very different from the actual situation. Assumption models of spectral emissivity exhibit drawbacks when used for thermometry of a complex material, or any material whose properties dynamically change during a combustion process. To address the above problems, in the present study, we developed a multispectral thermometry method based on optimisation ideas. This method involves analysing connections between measured temperatures of each channel in a multispectral temperature inversion process; it also makes use of correlations between multispectral signals at different temperatures. In short, we established a multivariate temperature difference correlation function based on the principles of multispectral radiometric thermometry, using information correlations between data for each channel in a temperature inversion process. We then established a high-precision thermometry model by optimising the correlation function and correcting any measurement errors. This method simplifies the modelling process so that it becomes an optimisation problem of the temperature difference function. This also removes the need to assume the relationships between spectral emissivity and other physical quantities, simplifying the process of multispectral thermometry. Finally, this involves correction of the spectral data so that any impact of measurement error on the thermometry is reduced. In order to verify the feasibility and reliability of the method, a simple eight-channel multispectral thermometry device was used for experimental validation, in which the temperature emitted from a blackbody furnace was identified as the standard value. In addition, spectral data from the 468-603 nm band were calibrated within a temperature range of 1923.15-2273.15 K, resulting in multispectral thermometry based on optimisation principles with an error rate of around 0.3% and a temperature calculation time of less than 3 s. The achieved level of inversion accuracy was better than that obtained using either a secondary measurement method (SMM) or a neural network method, and the calculation speed achieved was considerably faster than that obtained using the SMM method.

A transposon insertion in the promoter of OsUBC12 enhances cold tolerance during japonica rice germination.

Low-temperature germination (LTG) is an important agronomic trait for rice (Oryza sativa). Japonica rice generally has greater capacity for germination at low temperatures than the indica subpopulation. However, the genetic basis and molecular mechanisms underlying this complex trait are poorly understood. Here, we report that OsUBC12, encoding an E2 ubiquitin-conjugating enzyme, increases low-temperature germinability in japonica, owing to a transposon insertion in its promoter enhancing its expression. Natural variation analysis reveals that transposon insertion in the OsUBC12 promoter mainly occurs in the japonica lineage. The variation detected in eight representative two-line male sterile lines suggests the existence of this allele introgression by indica-japonica hybridization breeding, and varieties carrying the japonica OsUBC12 locus (transposon insertion) have higher low-temperature germinability than varieties without the locus. Further molecular analysis shows that OsUBC12 negatively regulate ABA signaling. OsUBC12-regulated seed germination and ABA signaling mainly depend on a conserved active site required for ubiquitin-conjugating enzyme activity. Furthermore, OsUBC12 directly associates with rice SUCROSE NON-FERMENTING 1-RELATED PROTEIN KINASE 1.1 (OsSnRK1.1), promoting its degradation. OsSnRK1.1 inhibits LTG by enhancing ABA signaling and acts downstream of OsUBC12. These findings shed light on the underlying mechanisms of UBC12 regulating LTG and provide genetic reference points for improving LTG in indica rice.

Transcriptome Profiling Reveals the Gene Network Responding to Low Nitrogen Stress in Wheat.

As one of the essential nutrients for plants, nitrogen (N) has a major impact on the yield and quality of wheat worldwide. Due to chemical fertilizer pollution, it has become increasingly important to improve crop yield by increasing N use efficiency (NUE). Therefore, understanding the response mechanisms to low N (LN) stress is essential for the regulation of NUE in wheat. In this study, LN stress significantly accelerated wheat root growth, but inhibited shoot growth. Further transcriptome analysis showed that 8468 differentially expressed genes (DEGs) responded to LN stress. The roots and shoots displayed opposite response patterns, of which the majority of DEGs in roots were up-regulated (66.15%; 2955/4467), but the majority of DEGs in shoots were down-regulated (71.62%; 3274/4565). GO and KEGG analyses showed that nitrate reductase activity, nitrate assimilation, and N metabolism were significantly enriched in both the roots and shoots. Transcription factor (TF) and protein kinase analysis showed that genes such as MYB-related (38/38 genes) may function in a tissue-specific manner to respond to LN stress. Moreover, 20 out of 107 N signaling homologous genes were differentially expressed in wheat. A total of 47 transcriptome datasets were used for weighted gene co-expression network analysis (17,840 genes), and five TFs were identified as the potential hub regulatory genes involved in the response to LN stress in wheat. Our findings provide insight into the functional mechanisms in response to LN stress and five candidate regulatory genes in wheat. These results will provide a basis for further research on promoting NUE in wheat.

Brassinosteroid-dependent phosphorylation of PHOSPHATE STARVATION RESPONSE2 reduces its DNA-binding ability in rice.

Brassinosteroids (BRs) are widely used as plant growth regulators in modern agriculture. Understanding how BRs regulate nutrient signaling is crucial for reducing fertilizer usage. Here we elucidate that the central BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 (GSK2) interacts directly with and phosphorylates PHOSPHATE STARVATION RESPONSE2 (OsPHR2), the key regulator of phosphate (Pi) signaling, to suppress its transcription factor activity in rice (Oryza sativa). We identify a critical phosphorylation site at serine residue S269 of OsPHR2 and demonstrate that phosphorylation by GSK2 or phosphor-mimic mutation of S269 substantially impairs the DNA-binding activity of OsPHR2, and thus diminishes expression of OsPHR2-induced genes and reduces Pi levels. Like BRs, Pi starvation noticeably induces GSK2 instability. We further show that this site-specific phosphorylation event is conserved in Arabidopsis (Arabidopsis thaliana), but varies among the PHR-family members, being present only in most land plants. These results unveil a distinctive post-transcriptional regulatory mechanism in Pi signaling by which BRs promote Pi acquisition, with a potential contribution to the environmental adaptability of plants during their evolution.

Tea polyphenols alleviate TBBPA-induced inflammation, ferroptosis and apoptosis via TLR4/NF-κB pathway in carp gills.

The extensive application of Tetrabromobisphenol A (TBBPA) leads to the pollution of part of the water environment and brings great safety risks to aquatic animals. As a natural extract, tea polyphenols (TPs) have antioxidant and anti-inflammatory effects. Gills are one of the immune organs of fish and constitute the first line of defense of the immune system. However, it was unclear whether TPs could mitigate TBBPA-induced gills injury. Therefore, an animal model was established to investigate the effect of TPs on TBBPA-induced gills. The results indicated that TBBPA changed the coefficient and tissue morphology of carp gills. In addition, TBBPA induced oxidative stress and inflammation, leading to ferroptosis and apoptosis in carp gills. Dietary addition of TPs significantly improved the antioxidant capacity of carp, effectively inhibited the overexpression of TLR4/NF-κB and its mediated inflammatory response. Moreover, TPs restored iron metabolism, reduced the expression of pro-apoptotic factors thereby alleviating ferroptosis and apoptosis in carp gills. This study enriched the protective effect of TPs and provided a new way to improve the innate immunity of carp.

Polyethylene microplastics cause apoptosis via the MiR-132/CAPN axis and inflammation in carp ovarian.

Microplastics (MPs) are widely distributed pollutants in the environment and accumulate in the aquatic environment due to human activities. Carp, a common edible aquatic organism, has been found to accumulate MPs in body. MicroRNA (miRNAs) is a non-coding short RNA that regulates protein expression by binding to target genes in various physiological processes such as proliferation, differentiation and apoptosis. The ovary is a crucial role in carp reproduction. In this study, we established a model of carp exposed to polyethylene microplastics (PE-MPs) in the aquatic environment to investigate the specific mechanism of PE-MPs causing ovarian injury and the involvement of miR-132/calpain (CAPN) axis. H&E stained sections revealed that PE-PMs induced inflammation in ovarian tissues and impaired oocyte development. TUNEL analysis showed an increased rate of apoptosis in ovarian cells treated with PE-PMs. RT-PCR and Western Blot assays confirmed that exposure to PE-MPs significantly decreased miR-132 expression while increasing CAPN expression at both mRNA and protein levels. The concentration of calcium ions was significantly increased in tissues, leading to CAPN enzyme activity increase. The expression of mitochondrial damage-related genes (bax, AIF, cyt-c, caspase-7, caspase-9, and caspase-3) was higher while the expression of anti-apoptotic genes (bcl-2 and bcl-xl) was lower. Protein levels of bax, AIF, caspase-3, bcl-2 and bcl-xl changed accordingly with the genetic alterations. Additionally, we discovered that PE-MPs can activate the p65 factor through the TRAF6/NF-kB pathway resulting in elevated production of pro-inflammatory factors IL-6, IL-1ß and TNF-a which contribute to ovarian inflammation development. This study investigates the impact of PE-MPs on carp ovarian function and provides insights into miRNAs' role and their target genes.

Synthesis and application of a compound microbial inoculant for effective soil remediation.

Currently, there is a noticeable scarcity of applications that harness composite microbial inoculants to stimulate straw decomposition, nitrogen fixation, and crop growth. This study addresses this gap by selecting and coculturing three bacterial strains to create a composite microbial inoculant named HY-1. This innovative inoculant exhibits multifunctional capabilities, including nitrogen fixation, straw decomposition, and crop growth promotion. Furthermore, we aimed to explore its impact on soil microbial communities. The results showed that the optimal preparation conditions for the compound microbial inoculant HY-1 were 28.5 ± 0.6 °C, pH = 7.34 ± 0.40, and bacteriophage ratio 1:2:1 (Microbacterium: Streptomyces fasciatus: Bacillus amyloliquefaciens). Compared to single strains, the combination exhibited higher levels of cellulose-degrading and nitrogen-fixing enzyme activity, increased the straw degradation rate by 37.91% within 180 days, and significantly promoted the growth of corn seedlings. Under the condition of straw return, the compound bio-fungicide HY-1 effectively improved the soil microbial diversity. At that time, the soil had the highest number of unique bacterial operational taxonomic units (166), and the abundance of Proteobacteria in the soil increased by 7.24%, while that of Acidobacteriota decreased by 2.27%. The biosynthetic function of the cell wall/membrane/periplasm and the metabolic function of transporting inorganic ions were significantly enhanced. In this study, we discovered that employing coculturing techniques to produce the composite microbial inoculant HY-1 and applying it in the field effectively compensates for the limitations of single-strain inoculants, which often exhibit fewer functions and less pronounced effects. This approach demonstrates significant potential for enhancing the quality of agricultural soils.

Pangenome analysis reveals genomic variations associated with domestication traits in broomcorn millet.

Broomcorn millet (Panicum miliaceum L.) is an orphan crop with the potential to improve cereal production and quality, and ensure food security. Here we present the genetic variations, population structure and diversity of a diverse worldwide collection of 516 broomcorn millet genomes. Population analysis indicated that the domesticated broomcorn millet originated from its wild progenitor in China. We then constructed a graph-based pangenome of broomcorn millet based on long-read de novo genome assemblies of 32 representative accessions. Our analysis revealed that the structural variations were highly associated with transposable elements, which influenced gene expression when located in the coding or regulatory regions. We also identified 139 loci associated with 31 key domestication and agronomic traits, including candidate genes and superior haplotypes, such as LG1, for panicle architecture. Thus, the study's findings provide foundational resources for developing genomics-assisted breeding programs in broomcorn millet.

Dural Reconstruction Materials for the Repairing of Spinal Neoplastic Cerebrospinal Fluid Leaks.

Spinal tumors often lead to more complex complications than other bone tumors. Nerve injuries, dura mater defect, and subsequent cerebrospinal fluid (CSF) leakage generally appear in spinal tumor surgeries and are followed by serious adverse outcomes such as infections and even death. The use of suitable dura mater replacements to achieve multifunctionality in fluid leakage plugging, preventing adhesions, and dural reconstruction is a promising therapeutic approach. Although there have been innovative endeavors to manage dura mater defects, only a handful of materials have realized the targeted multifunctionality. Here, we review recent advances in dura repair materials and techniques and discuss the relative merits in both preclinical and clinical trials as well as future therapeutic options. With these advances, spinal tumor patients with dura mater defects may be able to benefit from novel treatments.

Triggering Gaussian-to-Exponential Transition of Displacement Distribution in Polymer Nanocomposites via Adsorption-Induced Trapping.

In many disordered systems, the diffusion of classical particles is described by a displacement distribution P(x, t) that displays exponential tails instead of Gaussian statistics expected for Brownian motion. However, the experimental demonstration of control of this behavior by increasing the disorder strength has remained challenging. In this work, we explore the Gaussian-to-exponential transition by using diffusion of poly(ethylene glycol) (PEG) in attractive nanoparticle-polymer mixtures and controlling the volume fraction of the nanoparticles. In this work, we find "knobs", namely nanoparticle concentration and interaction, which enable the change in the shape of P(x,t) in a well-defined way. The Gaussian-to-exponential transition is consistent with a modified large deviation approach for a continuous time random walk and also with Monte Carlo simulations involving a microscopic model of polymer trapping via reversible adsorption to the nanoparticle surface. Our work bears significance in unraveling the fundamental physics behind the exponential decay of the displacement distribution at the tails, which is commonly observed in soft materials and nanomaterials.

Dracorhodin targeting CMPK2 attenuates inflammation: A novel approach to sepsis therapy.

BACKGROUND: Despite all modern advances in medicine, an effective drug for treating sepsis has yet to be found. The discovery of CMPK2 spurred hopes for the treatment of sepsis. However, CMPK2-untapped target inhibitors are still an enormous obstacle that has hindered the CMPK2-centric treatment of sepsis. METHODS: Here, we found that the CMPK2 gene is highly expressed in the whole blood of sepsis patients by RNA-Seq. First, recombinant CMPK2 was purified by a eukaryotic expression purification system, and the activity of recombinant CMPK2 was detected by the ADP-GLO assay. Second, we developed an affinity MS strategy combined with quantitative lysine reactivity profiling to discover CMPK2 ligands from the active ingredients of Chinese herbs. In addition, the dissociation constant Kd of the ligand and the target protein CMPK2 was further detected by microscale thermophoresis technology. Third, we used this strategy to identify a naturally sourced small molecule, dracorhodin (DP). Using mass spectrometry-based quantitative lysine reactivity profiling combined with a series of mutant tests, the results show that K265 acts as a bright hotspot of DP inhibition of CMPK2. Fourth, immune-histochemical staining, ELISAs, RT-qPCR, flow cytometry and immunoblotting were used to illustrate the potential function and related mechanism of DP in regulating sepsis injury. RESULTS: Our results suggest that DP exerts powerful anti-inflammatory effects by regulating the NLRP3 inflammasome via the lipopolysaccharide (LPS)-induced CMPK2 pathway. Strikingly, DP significantly attenuated LPS-induced sepsis in a mouse model, but its effect was weakened in mice with myeloid-specific Cmpk2 ablation. CONCLUSION: We provide a new framework that provides more valuable information for new therapeutic approaches to sepsis, including the establishment of screening strategies and the development of target drugs to provide a theoretical basis for ultimately improving clinical outcomes for sepsis patients. Collectively, these findings reveal that DP is a promising CMPK2 inhibitor for the treatment of sepsis.

Engineered rare-earth nanomaterials for fluorescence imaging and therapy.

Early diagnosis and treatment are of great significance for hindering the progression of brain disease. The limited effects of available treatments and poor prognosis are currently the most pressing problems faced by clinicians and their patients. Therefore, developing new diagnosis and treatment programs for brain diseases is urgently needed. Near-infrared (NIR)-light-responsive, lanthanide-doped upconversion nanoparticles (UCNPs) provide great advantages both in diagnosis and therapy. Hence, we synthesised nanoparticles comprised of a UCNPs core with surface functionalization. UCNPs@Au was used for NIR fluorescence imaging in the brain and inhibiting the growth of mouse glioma 261 (GL261) cells depending on photothermal properties. In addition, a UCNPs core and a mesoporous silica layer as the outer shell with a tannic acid-Al3+ ions (TA-Al) complex as a "gatekeeper" were used for pH-triggered doxorubicin/small interfering ribonucleic acid delivery in vitro. Based on our preliminary results, we expect to develop more multifunctional nanoscale diagnostic and therapeutic agents based on UCNPs for the diagnosis and treatment of brain diseases, including Alzheimer's disease, Parkinson's disease, and brain tumours.

Glycolysis-related biomarker TCIRG1 participates in regulation of renal cell carcinoma progression and tumor immune microenvironment by affecting aerobic glycolysis and AKT/mTOR signaling pathway.

BACKGROUND: Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC). METHODS: Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments. RESULTS: It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4+T cell Th1, CD8+T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines. CONCLUSIONS: Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.

Two complementary genes in a presence-absence variation contribute to indica-japonica reproductive isolation in rice.

Understanding the evolutionary forces in speciation is a central goal in evolutionary biology. Asian cultivated rice has two subspecies, indica and japonica, but the underlying mechanism of the partial reproductive isolation between them remains obscure. Here we show a presence-absence variation (PAV) at the Se locus functions as an indica-japonica reproductive barrier by causing hybrid sterility (HS) in indica-japonica crosses. The locus comprises two adjacent genes: ORF3 encodes a sporophytic pollen killer, whereas ORF4 protects pollen in a gametophytic manner. In F1 of indica-japonica crosses, pollen with the japonica haplotype, which lacks the sequence containing the protective ORF4, is aborted due to the pollen-killing effect of ORF3 from indica. Evolutionary analysis suggests ORF3 is a gene associated with the Asian cultivated rice species complex, and the PAV has contributed to the reproductive isolation between the two subspecies of Asian cultivated rice. Our analyses provide perspectives on rice inter-subspecies post-zygotic isolation, and will promote efforts to overcome reproductive barriers in indica-japonica hybrid rice breeding.

Simulation of pollutant diffusion in vegetation open channel based on LBM-CA method.

This paper proposes a pollution diffusion model that accurately assesses changes in instantaneous river pollution in vegetation open channels. The model is established based on cellular automata and lattice Boltzmann method (LBM-CA). Flow influence coefficients are incorporated into cellular automata (CA) to represent the effect of vegetation on pollutant diffusion, while the lattice Boltzmann method (LBM) is utilized to simulate flow in vegetation open channels and obtain the flow influence coefficients for each cellular. The results show that the LBM-CA model has high accuracy and that pollutants tend to accumulate in vegetation areas, thereby extending the residence time of pollutants. The model incorporates pollution limits, allowing the prediction of basin pollution levels at specific times. The LBM-CA model provides a method for simulating pollutant diffusion in natural rivers.

Construction and validation of a prognostic model for predicting clear cell renal cell carcinoma based on complement-related genes.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous tumor and is the most common subtype of renal cell carcinoma (RCC). Surgery is used to cure most early ccRCC, but the 5-year overall survival (OS) of ccRCC patients is far from satisfactory. Thus, new prognostic features and therapeutic targets for ccRCC need to be identified. Since complement factors can influence tumor development, we aimed to develop a model to predict the prognosis of ccRCC through complement-related genes. Methods: Differentially expressed genes were screened from an International Cancer Genome Consortium (ICGC) data set, and the genes associated with prognosis were screened by univariate regression and least absolute shrinkage and selection operator-Cox regression, and column line plots were generated using the rms R package to predict OS. The C-index was used to show the accuracy of the survival prediction and the prediction effects were verified using a data set from The Cancer Genome Atlas (TCGA). An immuno-infiltration analysis was performed with CIBERSORT analysis, and a drug sensitivity analysis was performed using the Gene Set Cancer Analysis (GSCA) (http://bioinfo.life.hust.edu.cn/GSCA/#/) database. Results: We identified 5 complement-related genes (i.e., A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4) for risk-score modeling to predict OS at 1, 2, 3, and 5 years, and the C-index of the prediction mode was 0.795. In addition, the model was successfully validated in TCGA data set. The CIBERSORT analysis showed that M1 macrophages were downregulated in the high-risk group. The GSCA database analysis showed that DOCK4, COL4A2, and A2M were positively correlated with the half maximal inhibitory concentration (IC50) of 10 drugs and small molecules, and COL4A2, NOTCH4, A2M, and APOBEC3G were negatively correlated with the IC50 of dozens of different drugs and small molecules. Conclusions: We developed and validated a survival prognostic model based on 5 complement-related genes for ccRCC. We also elucidated the relationship with tumor immune status and developed a new predictive tool for clinical purposes. In addition, our results showed that A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4 may be potential targets for the treatment of ccRCC in the future.

Genomic decoding of breeding history to guide breeding-by-design in rice.

Deciphering the intrinsic molecular logic of empirical crop breeding from a genomic perspective is a decisive prerequisite for breeding-by-design (BbD), but remains not well established. Here, we decoded the historical features of past rice breeding by phenotyping and haplotyping 546 accessions covering the majority of cultivars bred in the history of Northeast China (NEC). We revealed that three groups founded the genetic diversities in NEC rice with distinct evolution patterns and traced and verified the breeding footprints to known or genome-wide association study (GWAS)-detected quantitative trait loci (QTLs), or introgressions from indica sub-species with chronological changes in allele frequencies. Then we summarized a rice breeding trend/principle in NEC, and combined with the successful example in breeding and application of Zhongkefa5 to demonstrate the guiding value of our conclusion for BbD in practice. Our study provides a paradigm for decoding the breeding history of a specific crop to guide BbD, which may have implications in different crop breeding.

Human genetic history on the Tibetan Plateau in the past 5100 years.

Using genome-wide data of 89 ancient individuals dated to 5100 to 100 years before the present (B.P.) from 29 sites across the Tibetan Plateau, we found plateau-specific ancestry across plateau populations, with substantial genetic structure indicating high differentiation before 2500 B.P. Northeastern plateau populations rapidly showed admixture associated with millet farmers by 4700 B.P. in the Gonghe Basin. High genetic similarity on the southern and southwestern plateau showed population expansion along the Yarlung Tsangpo River since 3400 years ago. Central and southeastern plateau populations revealed extensive genetic admixture within the plateau historically, with substantial ancestry related to that found in southern and southwestern plateau populations. Over the past ~700 years, substantial gene flow from lowland East Asia further shaped the genetic landscape of present-day plateau populations. The high-altitude adaptive EPAS1 allele was found in plateau populations as early as in a 5100-year-old individual and showed a sharp increase over the past 2800 years.

The Discovery and Anti-Colorectal Cancer Activities of Cembranolides from the South China Sea Soft Coral Sinularia pendunculata.

A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (2-9), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.

Gankyrin-mediated interaction between cancer cells and tumor-associated macrophages facilitates prostate cancer progression and androgen deprivation therapy resistance.

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions. In vitro functional experiments and in vivo subcutaneous tumor models were used to explore the biological role and molecular mechanisms of gankyrin in prostate cancer cell-TAM interactions. 234 prostate cancer patients were randomly divided into training and validation cohorts to examine the prognostic value of gankyrin through immunohistochemistry (IHC) and statistical analyses, and high gankyrin expression was correlated with poor prognosis. In addition, gankyrin facilitated the progression and ADT resistance of prostate cancer. Mechanistically, gankyrin recruited and upregulated non-POU-domain-containing octamer-binding protein (NONO) expression, resulting in increased androgen receptor (AR) expression. AR then bound to the high-mobility group box 1 (HMGB1) promoter to trigger HMGB1 transcription, expression, and secretion. Moreover, HMGB1 was found to promote the recruitment and activation of TAMs, which secrete IL-6 to reciprocally promote prostate cancer progression, ADT resistance and gankyrin expression via STAT3, resulting in formation of a gankyrin/NONO/AR/HMGB1/IL-6/STAT3 positive feedback loop. Furthermore, targeting the interaction between tumor cells and TAMs by blocking this loop inhibited ADT resistance in a tumor xenograft model. Taken together, the data show that gankyrin serves as a reliable prognostic indicator and therapeutic target for prostate cancer patients.