CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Determinants of microbiome composition: Insights from free-ranging hybrid zebras (Equus quagga × grevyi).

The composition of mammalian gut microbiomes is highly conserved within species, yet the mechanisms by which microbiome composition is transmitted and maintained within lineages of wild animals remain unclear. Mutually compatible hypotheses exist, including that microbiome fidelity results from inherited dietary habits, shared environmental exposure, morphophysiological filtering and/or maternal effects. Interspecific hybrids are a promising system in which to interrogate the determinants of microbiome composition because hybrids can decouple traits and processes that are otherwise co-inherited in their parent species. We used a population of free-living hybrid zebras (Equus quagga × grevyi) in Kenya to evaluate the roles of these four mechanisms in regulating microbiome composition. We analysed faecal DNA for both the trnL-P6 and the 16S rRNA V4 region to characterize the diets and microbiomes of the hybrid zebra and of their parent species, plains zebra (E. quagga) and Grevy's zebra (E. grevyi). We found that both diet and microbiome composition clustered by species, and that hybrid diets and microbiomes were largely nested within those of the maternal species, plains zebra. Hybrid microbiomes were less variable than those of either parent species where they co-occurred. Diet and microbiome composition were strongly correlated, although the strength of this correlation varied between species. These patterns are most consistent with the maternal-effects hypothesis, somewhat consistent with the diet hypothesis, and largely inconsistent with the environmental-sourcing and morphophysiological-filtering hypotheses. Maternal transmittance likely operates in conjunction with inherited feeding habits to conserve microbiome composition within species.

Dynamic polarization fusion network (DPFN) for imaging in different scattering systems.

Deep learning has broad applications in imaging through scattering media. Polarization, as a distinctive characteristic of light, exhibits superior stability compared to light intensity within scattering media. Consequently, the de-scattering network trained using polarization is expected to achieve enhanced performance and generalization. For getting optimal outcomes in diverse scattering conditions, it makes sense to train expert networks tailored for each corresponding condition. Nonetheless, it is often unfeasible to acquire the corresponding data for every possible condition. And, due to the uniqueness of polarization, different polarization information representation methods have different sensitivity to different environments. As another of the most direct approaches, a generalist network can be trained with a range of polarization data from various scattering situations, however, it requires a larger network to capture the diversity of the data and a larger training set to prevent overfitting. Here, in order to achieve flexible adaptation to diverse environmental conditions and facilitate the selection of optimal polarization characteristics, we introduce a dynamic learning framework. This framework dynamically adjusts the weights assigned to different polarization components, thus effectively accommodating a wide range of scattering conditions. The proposed architecture incorporates a Gating Network (GTN) that efficiently integrates multiple polarization features and dynamically determines the suitable polarization information for various scenarios. Experimental result demonstrates that the network exhibits robust generalization capabilities across continuous scattering conditions.

Polarization motivating high-performance weak targets' imaging based on a dual-discriminator GAN.

High-level detection of weak targets under bright light has always been an important yet challenging task. In this paper, a method of effectively fusing intensity and polarization information has been proposed to tackle this issue. Specifically, an attention-guided dual-discriminator generative adversarial network (GAN) has been designed for image fusion of these two sources, in which the fusion results can maintain rich background information in intensity images while significantly completing target information from polarization images. The framework consists of a generator and two discriminators, which retain the texture and salient information as much as possible from the source images. Furthermore, attention mechanism is introduced to focus on contextual semantic information and enhance long-term dependency. For preserving salient information, a suitable loss function has been introduced to constrain the pixel-level distribution between the result and the original image. Moreover, the real scene dataset of weak targets under bright light has been built and the effects of fusion between polarization and intensity information on different weak targets have been investigated and discussed. The results demonstrate that the proposed method outperforms other methods both in subjective evaluations and objective indexes, which prove the effectiveness of achieving accurate detection of weak targets in bright light background.

Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling.

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.

Crystal-Site Engineering of Novel Na3KMg7(PO4)6-x(BO3)x:Eu2+ Phosphors for Full-Spectrum Lighting.

The "cyan gap" is the bottleneck problem in violet-driven full-spectrum white-light-emitting diodes (wLEDs) in healthy lighting. Accordingly, we develop a novel broadband-blue-cyan emission Na3KMg7(PO4)6-x(BO3)x:Eu2+ (NKMPB:Eu2+) phosphor via crystal-site engineering. This phosphor is derived from the Na3KMg7(PO4)6:Eu2+ phosphor, which shows desired abundant cyan emissive components. A comparative study is conducted to reveal the microstructure-property relationship and the key influential factors to its spectrum distribution. It can be found that the introduced (BO3)3- units can manipulate the site-selective occupation of Eu2+ activators, asymmetrically broadening the emission spectrum in NKMPB:Eu2+. Considering detailed luminescence performance analysis and the density functional theory calculations, a new substitution pathway of Eu2+ is created by substituting (PO4)3- with (BO3)3- units, making partial Eu2+ ions enter the Mg2+ (CN = 5, CN = 6) crystallographic sites, and yielding an extra emission band at 600 nm (16667 cm-1) and especially 501 nm (19960 cm-1). Meanwhile, a high-color-quality full-spectrum-emitting wLEDs was fabricated, upon 100 mA forward-bias current driven. Due to the achieved extra cyan emissive components of NKMPB:Eu2+, the constructed NKMPB:Eu2+-based wLEDs show better color rendering ability (∼90.9) than that of Na3KMg7(PO4)6:Eu2+-based wLEDs (∼86.3), and also demonstrate its great potential in full-spectrum healthy lighting.

Stable Mg Single-Atom Solid Base Catalysts Anchored on Metal-Organic Framework-Derived Nitrogen-Doped Carbon.

Solid base catalysts are widely used in the chemical industry owing to their advantages of environmental friendliness and easy separation. However, their application is limited by basic site aggregation and poor stability. In this study, we report the preparation of magnesium (Mg) single-atom catalysts with high activity and stability by a sublimation-trapping strategy. The Mg net was sublimated as Mg vapor at 620 °C, subsequently transported through argon, and finally trapped on the defects of nitrogen-doped carbon derived from metal-organic framework ZIF-8, producing Mg1/NC. Because of the atomically dispersed Mg sites, the obtained Mg1/NC exhibits high catalytic activity and stability for Knoevenagel condensation of benzaldehyde with malononitrile, which is a typical base-catalyzed reaction. The Mg1/NC catalyst achieves a high efficiency with a turnover frequency of 49.6 h-1, which is much better than that of the traditional counterpart MgO/NC (7.7 h-1). In particular, the activity of Mg1/NC shows no decrease after five catalytic cycles, while that of MgO/NC declines due to the instability of basic sites.

Construction of Nickel Single Atoms by Using the Inherent Confined Space in Template-Occupied Mesoporous Silica.

Due to their maximum atomic use of metal sites, single-atom catalysts (SACs) exhibit excellent catalytic activity in a variety of reactions. Although many techniques have been reported for the production of SACs, the construction of single atoms through a convenient strategy is still challenging. Here, we provide a facile method to prepare nickel SACs by utilizing the inherent confined space between the template and silica walls in template-occupied mesoporous silica KIT-6 (TOK). After the introduction of nickel-containing precursors into the inherent confined space of the TOK by solid-phase grinding, Ni SACs can be produced promptly during calcination. Single Ni atoms create a covalent Ni-O-Si structure in the TOK, as indicated by density functional theory (DFT) calculations and experimental data. This synthetic approach is easy to scale up, and 10 g of sample can be effortlessly synthesized using ball milling. The resultant Ni SACs were applied to the oxygen evolution reaction and exhibited higher catalytic activity and stability than the comparative sample synthesized in the absence of confined space.

Fenton-like system of UV/Glucose-oxidase@Kaolin coupled with organic green rust: UV-enhanced enzyme activity and the mechanism of UV synergistic degradation of photosensitive pollutants.

This study introduces the UV/glucose-oxidase@Kaolin (GOD@Kaolin) coupled organic green rust (OGR) system (UV/OGR/GOD@Kaolin) to investigate the promotion of glucose oxidase activity by UV light and its synergistic degradation mechanism for photosensitive pollutants, specifically targeting the efficient degradation of 4-chlorophenol (4-CP). The enzyme system demonstrates its ability to overcome drawbacks associated with traditional Fenton systems, including a narrow pH range and high localized concentration of H2O2, by gradually releasing hydrogen peroxide in situ within a neutral environment. In the presence of UV radiation under specific conditions, enhanced enzyme activity is observed, resulting in increased efficiency in pollutant removal. The gradual release of hydrogen peroxide plays a crucial role in preventing unwanted reactions among active substances. These unique features facilitate the generation of highly reactive species, such as Fe(IV)O, •OH, and •O2-, tailored to efficiently target the organic components of interest. Additionally, the system establishes a positive iron cycle, ensuring a sustained reactive capability throughout the degradation process. The results highlight the UV/OGR/GOD@Kaolin system as an effective and environmentally friendly approach for the degradation of 4-CP, and the resilience of the enzyme extends the system's applicability to a broader range of scenarios.

Deciphering the influence of salinity stress on the biological aniline degradation system: Pollutants degradation performance and microbial response.

In order to evaluate the impact of salinity gradients on the aniline biodegradation system, six reactors at salinity concentrations (0%-5%) were established. The results presented the salinity except for 5% imposed negligible effects on aniline degradation performance. Nitrification had prominent resistance to salinity (0%-1.5%) while were significantly restrained when salinity increased. The total nitrogen (TN) removal efficiency of Z4 (1.5%) was 20.5% higher than Z1 (0%) during the stable operation phase. Moreover, high throughput sequencing analysis showed that halophilic bacterium, such as Halomonas, Rhodococcus, remained greater survival advantages in high salinity system. The substantial enrichment of Flavobacterium, Dokdonella, Paracoccus observed in Z4 ensured its excellent nitrogen removal performance. The close cooperation among dominant functional bacteria was strengthened when salt content was below 1.5% while exceeding 1.5% led to the collapse of metabolic capacity through integrating the toxicity of aniline and high osmotic pressure.

Ochratoxin A detoxification potentials of basil, chan, and chia seeds.

The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds.

Lycium barbarum polysaccharide ameliorates the accumulation of lipid droplets in adipose tissue via an ATF6/SIRT1-dependent mechanism.

Lipid droplets (LDs) are dynamic organelles that store neutral lipids and are closely linked to obesity. Previous studies have suggested that Lycium barbarum polysaccharide (LBP) supplements can ameliorate obesity, but the underlying mechanisms remain unclear. In this study, we hypothesize that LBP alleviates LD accumulation in adipose tissue (AT) by inhibiting fat-specific protein 27 (Fsp27) through an activating transcription factor-6 (ATF6)/small-molecule sirtuin 1 (SIRT1)-dependent mechanism. LD accumulation in AT is induced in high-fat diet (HFD)-fed mice, and differentiation of 3T3-L1 preadipocytes (PAs) is induced. The ability of LBP to alleviate LD accumulation and the possible underlying mechanism are then investigated both in vivo and in vitro. The influences of LBP on the expressions of LD-associated genes ( ATF6 and Fsp27) are also detected. The results show that HFD and PA differentiation markedly increase LD accumulation in ATs and adipocytes, respectively, and these effects are markedly suppressed by LBP supplementation. Furthermore, LBP significantly activates SIRT1 and decreases ATF6 and Fsp27 expressions. Interestingly, the inhibitory effects of LBP are either abolished or exacerbated when ATF6 is overexpressed or silenced, respectively. Furthermore, SIRT1 level is transcriptionally regulated by LBP through opposite actions mediated by ATF6. Collectively, our findings suggest that LBP supplementation alleviates obesity by ameliorating LD accumulation, which might be partially mediated by an ATF6/SIRT1-dependent mechanism.

Biochemical and Transcriptome Analysis Reveals Pigment Biosynthesis Influenced Chlorina Leaf Formation in Anoectochilus roxburghii (Wall.) Lindl.

Anoectochilus roxburghii (Wall.) Lindl is a perennial herb of the Orchidaceae family; a yellow-green mutant and a yellow mutant were obtained from the wild type, thereby providing good material for the study of leaf color variation. Pigment content analysis revealed that chlorophyll, carotenoids, and anthocyanin were lower in the yellow-green and yellow mutants than in the wild type. Transcriptome analysis of the yellow mutant and wild type revealed that 78,712 unigenes were obtained, and 599 differentially expressed genes (120 upregulated and 479 downregulated) were identified. Using the Kyoto Encyclopedia of Genes and Genomes pathway analysis, candidate genes involved in the anthocyanin biosynthetic pathway (five unigenes) and the chlorophyll metabolic pathway (two unigenes) were identified. Meanwhile, the low expression of the chlorophyll and anthocyanin biosynthetic genes resulted in the absence of chlorophylls and anthocyanins in the yellow mutant. This study provides a basis for similar research in other closely related species.

Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.

Nitazoxanide inhibits acetylated KLF5-induced bone metastasis by modulating KLF5 function in prostate cancer.

BACKGROUND: Castration-resistant prostate cancer often metastasizes to the bone, and such bone metastases eventually become resistant to available therapies, leading to the death of patients. Enriched in the bone, TGF-ß plays a pivotal role in bone metastasis development. However, directly targeting TGF-ß or its receptors has been challenging for the treatment of bone metastasis. We previously found that TGF-ß induces and then depends on the acetylation of transcription factor KLF5 at K369 to regulate multiple biological processes, including the induction of EMT, cellular invasiveness, and bone metastasis. Acetylated KLF5 (Ac-KLF5) and its downstream effectors are thus potential therapeutic targets for treating TGF-ß-induced bone metastasis in prostate cancer. METHODS: A spheroid invasion assay was applied to prostate cancer cells expressing KLF5K369Q, which mimics Ac-KLF5, to screen 1987 FDA-approved drugs for invasion suppression. Luciferase- and KLF5K369Q-expressing cells were injected into nude mice via the tail artery to model bone metastasis. Bioluminescence imaging, micro-CT), and histological analyses were applied to monitor and evaluate bone metastases. RNA-sequencing, bioinformatic, and biochemical analyses were used to understand nitazoxanide (NTZ)-regulated genes, signaling pathways, and the underlying mechanisms. The binding of NTZ to KLF5 proteins was evaluated using fluorescence titration, high-performance liquid chromatography (HPLC), and circular dichroism (CD) analysis. RESULTS: NTZ, an anthelmintic agent, was identified as a potent invasion inhibitor in the screening and validation assays. In KLF5K369Q-induced bone metastasis, NTZ exerted a potent inhibitory effect in preventive and therapeutic modes. NTZ also inhibited osteoclast differentiation, a cellular process responsible for bone metastasis induced by KLF5K369Q. NTZ attenuated the function of KLF5K369Q in 127 genes' upregulation and 114 genes' downregulation. Some genes' expression changes were significantly associated with worse overall survival in patients with prostate cancer. One such change was the upregulation of MYBL2, which functionally promotes bone metastasis in prostate cancer. Additional analyses demonstrated that NTZ bound to the KLF5 protein, KLF5K369Q bound to the promoter of MYBL2 to activate its transcription, and NTZ attenuated the binding of KLF5K369Q to the MYBL2 promoter. CONCLUSIONS: NTZ is a potential therapeutic agent for bone metastasis induced by the TGF-ß/Ac-KLF5 signaling axis in prostate cancer and likely other cancers.

Endowing Covalent Organic Frameworks with Photoresponsive Active Sites for Controllable Propylene Adsorption.

Photoresponsive covalent organic frameworks (PCOFs) have emerged as attractive candidates for adsorption, but it is challenging to construct PCOF adsorbents due to structural order loss of covalent organic frameworks (COFs) after introducing photoresponsive motifs and/or tedious steps of postmodification. Here, a facile strategy is developed, by dispersing photoresponsive metal-organic polyhedra (PMOP) into COFs, to endow COFs with photoresponsive adsorption sites. As a proof-of-concept study, a COF with pore size of 4.5 nm and PMOP with suitable molecular size (4.0 and 3.1 nm for trans and cis configuration, respectively) are selected to meet the requirements of proper accommodation space, good guest dispersion, and free isomerization. The structure of COF is well preserved after introducing PMOPs. Interestingly, the obtained photoresponsive host-guest composite (PHGC) adsorbents exhibit photomodulated adsorption capacity on propylene (C3 H6 ) and the change in adsorption capacity can reach up to 43.3% and is stable during multiple cycles. Density functional theory calculations reveal that visible-light irradiation drives the azobenzene motifs in PHGCs to the trans configuration and the adsorption sites are fully open and interact with C3 H6 . UV-light irradiation makes the azobenzene motifs transform to the cis configuration, leading to the shield of the adsorption sites and the consequent release of C3 H6 .

Photo-Induced Construction and Recovery of Cu+ Sites in Metal-Organic Frameworks.

The adjustment of the valence state of metal ions is crucial for various applications because peculiar activity originates from metal ions with specific valence. Cu+ can interact with molecules possessing unsaturated bonds like CO via π-complexation, while Cu2+ doesn't have such ability. Meanwhile, Cu+ sites are easily oxidized to Cu2+ , leading to the loss of activity. Despite great efforts, the development of a facile method to construct and recover Cu+ sites remains a pronounced challenge. Here, for the first time a facile photo-induced strategy is reported to fabricate Cu+ sites in metal-organic frameworks (MOFs) and recover Cu+ after oxidation. The Cu2+ precursor was loaded on NH2 -MIL-125, a typical visible-light responsive Ti-based MOF. Visible light irradiation triggers the formation of Ti3+ from Ti4+ in framework, which reduces the supported Cu2+ in the absence of any additional reducing agent, thus simplifying the process for Cu+ generation significantly. Due to π-complexation interaction, the presence of Cu+ results in remarkably enhanced CO capture capacity (1.16 mmol g-1 ) compared to NH2 -MIL-125 (0.49 mmol g-1 ). More importantly, Cu+ can be recovered conveniently via re-irradiation when it is oxidized to Cu2+ , and the oxidation-recovery process is reversible.

A machine learning framework develops a DNA replication stress model for predicting clinical outcomes and therapeutic vulnerability in primary prostate cancer.

Recent studies have identified DNA replication stress as an important feature of advanced prostate cancer (PCa). The identification of biomarkers for DNA replication stress could therefore facilitate risk stratification and help inform treatment options for PCa. Here, we designed a robust machine learning-based framework to comprehensively explore the impact of DNA replication stress on prognosis and treatment in 5 PCa bulk transcriptomic cohorts with a total of 905 patients. Bootstrap resampling-based univariate Cox regression and Boruta algorithm were applied to select a subset of DNA replication stress genes that were more clinically relevant. Next, we benchmarked 7 survival-related machine-learning algorithms for PCa recurrence using nested cross-validation. Multi-omic and drug sensitivity data were also utilized to characterize PCa with various DNA replication stress. We found that the hyperparameter-tuned eXtreme Gradient Boosting model outperformed other tuned models and was therefore used to establish a robust replication stress signature (RSS). RSS demonstrated superior performance over most clinical features and other PCa signatures in predicting PCa recurrence across cohorts. Lower RSS was characterized by enriched metabolism pathways, high androgen activity, and a favorable prognosis. In contrast, higher RSS was significantly associated with TP53, RB1, and PTEN deletion, exhibited increased proliferation and DNA replication stress, and was more immune-suppressive with a higher chance of immunotherapy response. In silico screening identified 13 potential targets (e.g. TOP2A, CDK9, and RRM2) from 2249 druggable targets, and 2 therapeutic agents (irinotecan and topotecan) for RSS-high patients. Additionally, RSS-high patients were more responsive to taxane-based chemotherapy and Poly (ADP-ribose) polymerase inhibitors, whereas RSS-low patients were more sensitive to androgen deprivation therapy. In conclusion, a robust machine-learning framework was used to reveal the great potential of RSS for personalized risk stratification and therapeutic implications in PCa.

Process-Oriented Smart Adsorbents: Tailoring the Properties Dynamically as Demanded by Adsorption/Desorption.

Adsorptive separation plays a critical role in chemical, food, pharmaceutical, and environmental industries, as well as in many other industrial areas. Adsorbents are most important for adsorptive separation and undergo adsorption and desorption processes to accomplish the specific tasks of separation. In the process of adsorption, adsorbates diffuse into the pore spaces of adsorbents through pore openings, adsorb on active sites via physical or chemical interactions, and subsequently are regenerated by temperature or pressure swings during desorption. In the process of adsorption and desorption, however, the requirements for pore structures and surface properties of adsorbents are different. In general, adsorbents with small pore openings can realize selective adsorption and do not favor desorption; on the other hand, adsorbents with large pore openings are efficient in desorption but at the expense of adsorption selectivity. Remarkably, active sites possessing strong interactions with adsorbates contribute to high selectivity for adsorption, while desorption becomes difficult. The trade-off between adsorption and desorption presents an enormous challenge to develop high-efficiency adsorbents. Restricted by their fixed structures and surface properties, conventional adsorbents are unable to meet the demands of adsorption and desorption processes simultaneously.To confront the obstacles, the development of advanced adsorbents to meet the demand of adsorptive separation are urgent. A key strategy to address such issues lies in dynamically adjusting the pore structures or the surface properties of adsorbents with controllability according to the demands of adsorption/desorption. For instance, pursuant to the requirements of varying pore structures during adsorption/desorption, the pore openings of adsorbents can be customized through dynamic structural change of the decorated stimuli-sensitive motifs by suitable external intervention. In addition, the active sites within the adsorbents can be exposed to enhance the adsorption selectivity or sheltered to accelerate the desorption through stimuli-triggered adsorbent-adsorbate interactions. Hence, we proposed a concept of process-oriented smart adsorbents (POSAs) on the basis of the requirements of the adsorption/desorption processes. The design and development of such POSAs are based on three aspects, namely, pore openings, pore spaces, and adsorption sites of adsorbents.In this Account, we present the progress in the development of POSAs according to the demands of adsorption/desorption processes. A series of POSAs with incorporated stimuli-sensitive motifs were successfully achieved. The versatility of incorporated motifs allows them to tune the pore structures and surface properties of adsorbents dynamically and further to enhance the adsorption and desorption efficiency simultaneously. Based on the concept of POSAs, we hope that this Account could contribute to the development of high-efficiency adsorbents and ultimately promote their applications in practical industrial separation. Moreover, we present an outlook on future trends and challenges on the road toward the development and applications of POSAs.

Self-attention module in a multi-scale improved U-net (SAM-MIU-net) motivating high-performance polarization scattering imaging.

Polarization imaging has outstanding advantages in the field of scattering imaging, which still encounters great challenges in heavy scattering media systems even though there are helps from deep learning technology. In this paper, we propose a self-attention module (SAM) in multi-scale improved U-net (SAM-MIU-net) for the polarization scattering imaging, which can extract a new combination of multidimensional information from targets effectively. The proposed SAM-MIU-net can focus on the stable feature carried by polarization characteristics of the target, so as to enhance the expression of the available features, and make it easier to extract polarization features which help to recover the detail of targets for the polarization scattering imaging. Meanwhile, the SAM's effectiveness has been verified in a series of experiments. Based on proposed SAM-MIU-net, we have investigated the generalization abilities for the targets' structures and materials, and the imaging distances between the targets and the ground glass. Experimental results demonstrate that our proposed SAM-MIU-net can achieve high-precision reconstruction of target information under incoherent light conditions for the polarization scattering imaging.