Structural basis for the tethered peptide activation of adhesion GPCRs.

Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes1-6. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence7-12. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with Gs: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-ß-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W6.53 and the constitution of a hydrogen-bond network formed by Q7.49/Y7.49 and the P6.47/V6.47φφG6.50 motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and Gs coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common Gs-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with Gs. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their Gs coupling.

Structure, function and pharmacology of human itch receptor complexes.

In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals1,2. As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions3-6. MRGPRX2 has been targeted by drug development efforts to prevent the side effects induced by certain drugs or to treat allergic diseases. Here we report a set of cryo-electron microscopy structures of the MRGPRX2-Gi1 trimer in complex with polycationic compound 48/80 or with inflammatory peptides. The structures of the MRGPRX2-Gi1 complex exhibited shallow, solvent-exposed ligand-binding pockets. We identified key common structural features of MRGPRX2 and describe a consensus motif for peptidic allergens. Beneath the ligand-binding pocket, the unusual kink formation at transmembrane domain 6 (TM6) and the replacement of the general toggle switch from Trp6.48 to Gly6.48 (superscript annotations as per Ballesteros-Weinstein nomenclature) suggest a distinct activation process. We characterized the interfaces of MRGPRX2 and the Gi trimer, and mapped the residues associated with key single-nucleotide polymorphisms on both the ligand and G-protein interfaces of MRGPRX2. Collectively, our results provide a structural basis for the sensing of cationic allergens by MRGPRX2, potentially facilitating the rational design of therapies to prevent unwanted pseudoallergic reactions.

Genome evolution of the ancient hexaploid Platanus × acerifolia (London planetree).

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms.

Proteomic characterization of isolated Arabidopsis clathrin-coated vesicles reveals evolutionarily conserved and plant-specific components.

In eukaryotes, clathrin-coated vesicles (CCVs) facilitate the internalization of material from the cell surface as well as the movement of cargo in post-Golgi trafficking pathways. This diversity of functions is partially provided by multiple monomeric and multimeric clathrin adaptor complexes that provide compartment and cargo selectivity. The adaptor-protein assembly polypeptide-1 (AP-1) complex operates as part of the secretory pathway at the trans-Golgi network (TGN), while the AP-2 complex and the TPLATE complex jointly operate at the plasma membrane to execute clathrin-mediated endocytosis. Key to our further understanding of clathrin-mediated trafficking in plants will be the comprehensive identification and characterization of the network of evolutionarily conserved and plant-specific core and accessory machinery involved in the formation and targeting of CCVs. To facilitate these studies, we have analyzed the proteome of enriched TGN/early endosome-derived and endocytic CCVs isolated from dividing and expanding suspension-cultured Arabidopsis (Arabidopsis thaliana) cells. Tandem mass spectrometry analysis results were validated by differential chemical labeling experiments to identify proteins co-enriching with CCVs. Proteins enriched in CCVs included previously characterized CCV components and cargos such as the vacuolar sorting receptors in addition to conserved and plant-specific components whose function in clathrin-mediated trafficking has not been previously defined. Notably, in addition to AP-1 and AP-2, all subunits of the AP-4 complex, but not AP-3 or AP-5, were found to be in high abundance in the CCV proteome. The association of AP-4 with suspension-cultured Arabidopsis CCVs is further supported via additional biochemical data.

Genome-wide Association Study of Exercise-induced Skeletal Muscle Hypertrophy and the Construction of Predictive Model.

To investigate inter-individual differences in muscle thickness of Rectus Femoris (MTRF) following 12 weeks of Resistance Training (RT) or High-Intensity Interval Training (HIIT) to explore the genetic architecture underlying skeletal muscle hypertrophy and to construct predictive models. We conducted musculoskeletal ultrasound assessments of the MTRF response in 440 physically inactive adults after the 12-week exercise period. A Genome-wide Association study (GWAS) was employed to identify variants associated with MTRF response, separately for RT and HIIT. Utilizing polygenic predictor score (PPS), we estimated the genetic contribution to exercise-induced hypertrophy. Predictive models for MTRF response were constructed using Random Forest (RF), Support Vector Mac (SVM), and Generalized Linear Model (GLM) in 10 cross-validated approach. MTRF increased significantly after both RT (8.8%, P<0.05) and HIIT (5.3%, P<0.05), but with considerable inter-individual differences (RT: -13.5~38.4%, HIIT: -14.2%~30.7%). Eleven lead SNPs in RT and eight lead SNPs in HIIT were identified at a significance level of P<1×10-5. The PPS was associated with MTRF response, explaining 47.2% of the variation in response to RT and 38.3% of the variation in response to HIIT. Notably, the GLM and SVM predictive models exhibited superior performance in comparison to RF models (p<0.05), and the GLM demonstrated optimal performance with an AUC of 0.809 (95%CI:0.669-0.949). Factors such as PPS, baseline MTRF, and exercise protocol exerted influence on the MTRF response to exercise, with PPS being the primary contributor. The GLM and SVM predictive model, incorporating both genetic and phenotypic factors, emerged as promising tools for predicting exercise-induced skeletal muscle hypertrophy.

Small peptides: could they have a big role in metabolism and the response to exercise?

Exercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mechanisms responsible for the many beneficial adaptations to exercise. This has led to increased research into the role of small peptides (<100 amino acids) and mitochondrially derived peptides in metabolism and disease, including those coded within small open reading frames (sORFs; coding sequences that encode small peptides). Recently, it has been hypothesized that sORF-encoded mitochondrially derived peptides and other small peptides play significant roles as exercise-sensitive peptides in exercise-induced physiological adaptation. In this review, we highlight the discovery of mitochondrially derived peptides and newly discovered small peptides involved in metabolism, with a specific emphasis on their functions in exercise-induced adaptations and the prevention of metabolic diseases. In light of the few studies available, we also present data on how both single exercise sessions and exercise training affect expression of sORF-encoded mitochondrially derived peptides. Finally, we outline numerous research questions that await investigation regarding the roles of mitochondrially derived peptides in metabolism and prevention of various diseases, in addition to their roles in exercise-induced physiological adaptations, for future studies.

Transcriptome reveals the roles and potential mechanisms of lncRNAs in the regulation of albendazole resistance in Haemonchus contortus.

BACKGROUND: Haemonchus contortus (H. contortus) is the most common parasitic nematode in ruminants and is prevalent worldwide. H. contortus resistance to albendazole (ABZ) hinders the efficacy of anthelmintic drugs, but little is known about the molecular mechanisms that regulate this of drug resistance. Recent research has demonstrated that long noncoding RNAs (lncRNAs) can exert significant influence as pivotal regulators of the emergence of drug resistance. RESULTS: In this study, transcriptome sequencing was conducted on both albendazole-sensitive (ABZ-sensitive) and albendazole-resistant (ABZ-resistant) H. contortus strains, with three biological replicates for each group. The analysis of lncRNA in the transcriptomic data revealed that there were 276 differentially expressed lncRNA (DElncRNA) between strains with ABZ-sensitive and ABZ-resistant according to the criteria of |log2Foldchange|≥ 1 and FDR < 0.05. Notably, MSTRG.12969.2 and MSTRG.9827.1 exhibited the most significant upregulation and downregulation, respectively, in the resistant strains. The potential roles of the DElncRNAs included catalytic activity, stimulus response, regulation of drug metabolism, and modulation of the immune response. Moreover, we investigated the interactions between DElncRNAs and other RNAs, specifically MSTRG.12741.1, MSTRG.11848.1, MSTRG.5895.1, and MSTRG.14070.1, involved in regulating drug stimulation through cis/trans/antisense/lncRNA‒miRNA-mRNA interaction networks. This regulation leads to a decrease (or increase) in the expression of relevant genes, consequently enhancing the resistance of H. contortus to albendazole. Furthermore, through comprehensive analysis of competitive endogenous RNAs (ceRNAs) involved in drug resistance-related pathways, such as the mTOR signalling pathway and ABC transporter signalling pathway, the relevance of the MSTRG.2499.1-novel-m0062-3p-HCON_00099610 interaction was identified to mainly involve the regulation of catalytic activity, metabolism, ubiquitination and transcriptional regulation of gene promoters. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) validation indicated that the transcription profiles of six DElncRNAs and six DEmRNAs were consistent with those obtained by RNA-seq. CONCLUSIONS: The results of the present study allowed us to better understand the changes in the lncRNA expression profile of ABZ-resistant H. contortus. In total, these results suggest that the lncRNAs MSTRG.963.1, MSTRG.12741.1, MSTRG.11848.1 and MSTRG.2499.1 play important roles in the development of ABZ resistance and can serve as promising biomarkers for further study.

Injectable Hydrogels Including Magnetic Nanosheets for Multidisciplinary Treatment of Hepatocellular Carcinoma via Magnetic Hyperthermia.

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

Improved optical contrast of plasmonic phase change memory using a Fabry-Perot cavity.

As a promising technology to realize multilevel, non-volatile data storage and information processing, optical phase change technologies have attracted extensive attention in recent years. However, existing phase-change photonic devices face significant challenges such as limited switching contrast and high switching energy. This study introduces an innovative approach to tackle these issues by leveraging Fabry-Perot (F-P) cavity resonance and plasmon resonance techniques to enhance the modulation effect of phase change materials (PCMs) on the light. To the best of our knowledge, a novel device structure is proposed, featuring an elliptic nano-antenna placed on an F-P cavity waveguide composed of symmetric Bragg grating. This design exploits the enhanced electric field to achieve low power consumption and high contrast. The device enables crucial functions, including read, write, and erase operations, under all light conditions. Through the synergistic utilization of plasma and F-P cavity effects, an ultra-high switching contrast of around 70.6% is achieved. By varying the pulse power or duration, the proportion between the crystalline and amorphous states of the PCMs is altered, consequently modifying its refractive index. With its wide range of applications in optical storage and computing, the device holds significant potential for advancing these fields.

Nonvolatile multilevel adjustable optical switch based on plasmonic slot waveguide and GST segmented structure.

Optical computing has gradually demonstrated its efficiency in handling increasingly complex computational demands, attracting widespread attention. Optical switches can effectively control and modulate optical signals, providing flexibility and efficiency for optical computing systems. However, traditional optical switches face performance issues such as power consumption, switching speed, and compactness, severely limiting the implementation of large-scale photonic integrated circuits and optical neural networks. This paper proposes an innovative design structure for a non-volatile multi-level adjustable optical switch by combining a plasmonic slot waveguide with segmented phase-change materials. Modulation of waveguide light transmission is achieved by adjusting the phase state of Ge2Sb2Te5(GST). At a wavelength of 1550 nm, a low insertion loss of 0.5dB has been achieved, with approximately an 85% difference in optical transmittance between amorphous state (aGST) and crystalline state (cGST). The high transmittance difference contributes to achieving a wide range of weight variations and supports precise weight updates. Based on this design, we successfully implemented a handwritten digit recognition task with an accuracy of 95%, laying the foundation for future more efficient memory computing neural morphic networks.

Cross-talk between clathrin-dependent post-Golgi trafficking and clathrin-mediated endocytosis in Arabidopsis root cells.

Coupling of post-Golgi and endocytic membrane transport ensures that the flow of materials to/from the plasma membrane (PM) is properly balanced. The mechanisms underlying the coordinated trafficking of PM proteins in plants, however, are not well understood. In plant cells, clathrin and its adaptor protein complexes, AP-2 and the TPLATE complex (TPC) at the PM, and AP-1 at the trans-Golgi network/early endosome (TGN/EE), function in clathrin-mediated endocytosis (CME) and post-Golgi trafficking. Here, we utilized mutants with defects in clathrin-dependent post-Golgi trafficking and CME, in combination with other cytological and pharmacological approaches, to further investigate the machinery behind the coordination of protein delivery and recycling to/from the TGN/EE and PM in Arabidopsis (Arabidopsis thaliana) root cells. In mutants with defective AP-2-/TPC-dependent CME, we determined that clathrin and AP-1 recruitment to the TGN/EE as well as exocytosis are significantly impaired. Likewise, defects in AP-1-dependent post-Golgi trafficking and pharmacological inhibition of exocytosis resulted in the reduced association of clathrin and AP-2/TPC subunits with the PM and a reduction in the internalization of cargoes via CME. Together, these results suggest that post-Golgi trafficking and CME are coupled via modulation of clathrin and adaptor protein complex recruitment to the TGN/EE and PM.

Soluble Periostin is a potential surveillance biomarker for early and long-term response to chemotherapy in advanced breast cancer.

BACKGROUND: Noninvasive biomarkers for the assessment of response to chemotherapy in advanced breast cancer (BCa) are essential for optimized therapeutic decision-making. We evaluated the potential of soluble Periostin (POSTN) in circulation as a novel biomarker for chemotherapy efficacy monitoring. METHODS: Two hundred and thirty-one patients with different stages of BCa were included. Of those patients, 58 patients with inoperable metastatic disease receiving HER2-targeted or non-targeted chemotherapy were enrolled to assess the performances of markers in recapitulating the chemotherapy efficacy assessed by imaging. POSTN, together with CA153 or CEA at different time points (C0, C2, and C4) were determined. RESULTS: POSTN levels were significantly associated with tumor volume (P < 0.0001) and TNM stages (P < 0.0001) of BCa. For early monitoring, dynamics of POSTN could recapitulate the chemotherapy efficacy among all molecular subtypes (Cohen's weighted kappa = 0.638, P < 0.0001), much better than that of carcinoembryonic antigen (CEA) and cancer antigen 153 (CA15-3). For early partial response, superior performance of POSTN was observed (Cohen's weighted kappa = 0.827, P < 0.0001) in cases with baseline levels above 17.19 ng/mL. For long-term monitoring, the POSTN response was observed to be strongly consistent with the course of the disease. Moreover, progression free survival analysis showed that patients experienced a significant early decrease of POSTN tended to obtain more benefits from the treatments. CONCLUSIONS: The current study suggests that soluble POSTN is an informative serum biomarker to complement the current clinical approaches for early and long-term chemotherapy efficacy monitoring in advanced BCa.

Genome dosage alteration caused by chromosome pyramiding and shuffling effects on karyotypic heterogeneity, reproductive diversity, and phenotypic variation in Zea-Tripsacum allopolyploids.

KEY MESSAGE: We developed an array of Zea-Tripsacum tri-hybrid allopolyploids with multiple ploidies. We unveiled that changes in genome dosage due to the chromosomes pyramiding and shuffling of three species effects karyotypic heterogeneity, reproductive diversity, and phenotypic variation in Zea-Tripsacum allopolyploids. Polyploidy, or whole genome duplication, has played a major role in evolution and speciation. The genomic consequences of polyploidy have been extensively studied in many plants; however, the extent of chromosomal variation, genome dosage, phenotypic diversity, and heterosis in allopolyploids derived from multiple species remains largely unknown. To address this question, we synthesized an allohexaploid involving Zea mays, Tripsacum dactyloides, and Z. perennis by chromosomal pyramiding. Subsequently, an allooctoploid and an allopentaploid were obtained by hybridization of the allohexaploid with Z. perennis. Moreover, we constructed three populations with different ploidy by chromosomal shuffling (allopentaploid × Z. perennis, allohexaploid × Z. perennis, and allooctoploid × Z. perennis). We have observed 3 types of sexual reproductive modes and 2 types of asexual reproduction modes in the tri-species hybrids, including 2n gamete fusion (2n + n), haploid gamete fusion (n + n), polyspermy fertilization (n + n + n) or 2n gamete fusion (n + 2n), haploid gametophyte apomixis, and asexual reproduction. The tri-hybrids library presents extremely rich karyotype heterogeneity. Chromosomal compensation appears to exist between maize and Z. perennis. A rise in the ploidy of the trihybrids was linked to a higher frequency of chromosomal translocation. Variation in the degree of phenotypic diversity observed in different segregating populations suggested that genome dosage effects phenotypic manifestation. These findings not only broaden our understanding of the mechanisms of polyploid formation and reproductive diversity but also provide a novel insight into genome pyramiding and shuffling driven genome dosage effects and phenotypic diversity.

Janus Cr2BN Monolayer with Ferroelectricity and Room-Temperature Ferromagnetism.

Janus monolayers, a special kind of two-dimensional materials, offer an exciting platform for the development of novel electronic/spintronic devices because of their out-of-plane asymmetry. Herein, we propose a sandwich liked Janus tetragonal Cr2BN monolayer with ferroelectricity and ferromagnetism through first-principles calculations. The predicted magnetic moment is up to ~3.0 µB/Cr originating from the distorted square crystal field induced by out-of-plane asymmetry. The Cr2BN monolayer possesses an intrinsic ferromagnetism with a high Curie temperature of 383 K and a sizeable magnetic anisotropy energy of 171 µeV/Cr. Its robust ferromagnetism, dominating by the multi-anion mediated super-exchange interactions, can even resist -5 % ~5 % biaxial strain. Its large cohesive energy and high dynamical/thermal stability provide a strong feasibility for experimental synthesis. These intriguing properties render the Cr2BN monolayer a promising material for nanoscale spintronic devices.

Enhancing real-time cell culture monitoring: Automated Raman model optimization with Taguchi method.

Raman spectroscopy has found widespread usage in monitoring cell culture processes both in research and practical applications. However, commonly, preprocessing methods, spectral regions, and modeling parameters have been chosen based on experience or trial-and-error strategies. These choices can significantly impact the performance of the models. There is an urgent need for a simple, effective, and automated approach to determine a suitable procedure for constructing accurate models. This paper introduces the adoption of a design of experiment (DoE) method to optimize partial least squares models for measuring the concentration of different components in cell culture bioreactors. The experimental implementation utilized the orthogonal test table L25(56). Within this framework, five factors were identified as control variables for the DoE method: the window width of Savitzky-Golay smoothing, the baseline correction method, the order of preprocessing steps, spectral regions, and the number of latent variables. The evaluation method for the model was considered as a factor subject to noise. The optimal combination of levels was determined through the signal-to-noise ratio response table employing Taguchi analysis. The effectiveness of this approach was validated through two cases, involving different cultivation scales, different Raman spectrometers, and different analytical components. The results consistently demonstrated that the proposed approach closely approximated the global optimum, regardless of data set size, predictive components, or the brand of Raman spectrometer. The performance of models recommended by the DoE strategy consistently surpassed those built using raw data, underscoring the reliability of models generated through this approach. When compared to exhaustive all-combination experiments, the DoE approach significantly reduces calculation times, making it highly practical for the implementation of Raman spectroscopy in bioprocess monitoring.

Constructing a Titanium Silicon Molecular Sieve-Based Z-Scheme Heterojunction with Enhanced Photocatalytic Activity.

Titanium silicon molecular sieve (TS-1) is an oxidation catalyst that possesses a long lifetime of charge transfer excited state, high Ti utilization efficiency, large specific surface area, and good adsorption property; therefore, TS-1 acts as a Ti-based photocatalyst candidate. In this work, TS-1 coupled Bi2MoO6 (TS-1/BMO) photocatalysts were fabricated via a facile hydrothermal route. Interestingly, the optimized TS-1/BMO-1.0 catalyst exhibited a decent photodegradation property toward tetracycline hydrochloride (85.49% in 120 min) under the irradiation of full spectrum light, which were 4.38 and 1.76 times compared to TS-1 and BMO, respectively. The enhanced photodegradation property of the TS-1/BMO-1.0 catalyst could be attributed to the reinforced light-harvesting capacity of the photocatalyst, high charge mobility, and suitable band structure for tetracycline hydrochloride degradation. In addition, the mechanism of photocatalytic degradation of tetracycline hydrochloride by the TS-1/BMO-1.0 catalyst was reasonably proposed based on the band structure, trapping, and ESR tests. This research provided feasible ideas for the design and construction of high-efficiency photocatalysts for contaminant degradation.

Metal-Organic Frameworks Marry Sponge: New Opportunities for Advanced Water Treatment.

Metal-organic frameworks (MOFs) have garnered attention across various fields due to their noteworthy features like high specific surface area, substantial porosity, and adjustable performance. In the realm of water treatment, MOFs exhibit great potential for eliminating pollutants such as organics, heavy metals, and oils. Nonetheless, the inherent powder characteristics of MOFs pose challenges in terms of recycling, pipeline blockage, and even secondary pollution in practical applications. Addressing these issues, the incorporation of MOFs into sponges proves to be an effective solution. Strategies like one-pot synthesis, in situ growth, and impregnation are commonly employed for loading MOFs onto sponges. This review comprehensively explores the synthesis strategies of MOFs and sponges, along with their applications in water treatment, aiming to contribute to the ongoing advancement of MOF materials.

Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models.

OBJECTIVES: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC). METHODS: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, ßCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability. RESULTS: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877. CONCLUSIONS: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs. CLINICAL RELEVANCE STATEMENT: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue. KEY POINTS: • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.

High-performance presurgical differentiation of glioblastoma and metastasis by means of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics.

OBJECTIVES: To evaluate the performance of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics in distinguishing between glioblastoma (Gb) and solitary brain metastasis (SBM). MATERIALS AND METHODS: In this retrospective study, NODDI images were curated from 109 patients with Gb (n = 57) or SBM (n = 52). Automatically segmented multiple volumes of interest (VOIs) encompassed the main tumor regions, including necrosis, solid tumor, and peritumoral edema. Radiomics features were extracted for each main tumor region, using three NODDI parameter maps. Radiomics models were developed based on these three NODDI parameter maps and their amalgamation to differentiate between Gb and SBM. Additionally, radiomics models were constructed based on morphological magnetic resonance imaging (MRI) and diffusion imaging (diffusion-weighted imaging [DWI]; diffusion tensor imaging [DTI]) for performance comparison. RESULTS: The validation dataset results revealed that the performance of a single NODDI parameter map model was inferior to that of the combined NODDI model. In the necrotic regions, the combined NODDI radiomics model exhibited less than ideal discriminative capabilities (area under the receiver operating characteristic curve [AUC] = 0.701). For peritumoral edema regions, the combined NODDI radiomics model achieved a moderate level of discrimination (AUC = 0.820). Within the solid tumor regions, the combined NODDI radiomics model demonstrated superior performance (AUC = 0.904), surpassing the models of other VOIs. The comparison results demonstrated that the NODDI model was better than the DWI and DTI models, while those of the morphological MRI and NODDI models were similar. CONCLUSION: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM. CLINICAL RELEVANCE STATEMENT: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM, and radiomics features can be incorporated into the multidimensional phenotypic features that describe tumor heterogeneity. KEY POINTS: • The neurite orientation dispersion and density imaging (NODDI) radiomics model showed promising performance for preoperative discrimination between glioblastoma and solitary brain metastasis. • Compared with other tumor volumes of interest, the NODDI radiomics model based on solid tumor regions performed best in distinguishing the two types of tumors. • The performance of the single-parameter NODDI model was inferior to that of the combined-parameter NODDI model.

Regulatory roles of miRNA-530 in the post-transcriptional regulation of NF-κB signaling pathway through targeted modulation of IκBα in Sebastesschlegelii.

MicroRNAs (miRNAs) are a crucial type of non-coding RNAs involved in post-transcriptional regulation. The playing essential regulatory roles in the NF-κB signaling pathway and modulate the host immune response to diverse pathogens by targeting IκBα. However, the regulatory mechanism of miRNAs in relation with IκBα in Sebastes schlegelii remains unclear. In our study, we identified two copies of IkBα gene in black rockfish (Sebastes schlegelii), namely IkBα1 and IkBα2. Moreover, we have discovered that miRNA-530 can activate the NF-κB signaling pathway by inhibiting the expression of IκBα, thereby inducing the inflammatory response. This project comprehensively investigated the interactive regulatory roles of miRNA-530 in the NF-κB signaling pathway at both cellular and in vivo levels, while also elucidating the regulatory relationships between miRNA-530 and IκBα. In conclusion, our research confirmed that miRNA-530 can target the 3'UTR region of IκBα, resulting in a decrease in the expression of IκBα at the post-transcriptional level and inhibiting its translation. The findings contribute to the understanding of the regulatory network of non-coding RNA in teleosts and its subsequent regulation of the NF-κB signaling pathway by miRNAs.