Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

Transcriptional landscape of intestinal environment in DSS-induced ulcerative colitis mouse model.

Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.

Sodium humate ameliorates LPS-induced liver injury in mice by inhibiting TLR4/NF-κB and activating NRF2/HO-1 signaling pathways.

BACKGROUND: Acute liver damage is a type of liver disease that has a significant global occurrence and a lack of successful treatment and prevention approaches. Sodium humate (HNa), a natural organic substance, has extensive applications in traditional Chinese medicine due to its antibacterial, anti-diarrheal, and anti-inflammatory characteristics. The purpose of this research was to examine the mitigating impacts of HNa on liver damage induced by lipopolysaccharide (LPS) in mice. METHODS AND RESULTS: A total of 30 female mice were randomly assigned into Con, Mod, L-HNa, M-HNa, and H-HNa groups. Mice in the Con and Mod groups were gavaged with PBS, whereas L-HNa, M-HNa, and H-HNa groups mice were gavaged with 0.1%, 0.3%, and 0.5% HNa, daily. On day 21, Mod, L-HNa, M-HNa, and H-HNa groups mice were challenged with LPS (10 mg/kg). We discovered that pretreatment with HNa improved liver pathological damage and inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway, enhancing the polarization of liver M2 macrophages, and reducing the levels of inflammatory cytokines. Our further study found that pretreatment with HNa enhanced the liver ability to combat oxidative stress and reduced hepatocyte apoptosis by activating the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway and enhancing the activities of antioxidant enzymes. CONCLUSIONS: In conclusion, HNa could alleviate LPS-induced liver damage through inhibiting TLR4/NF-κB and activating NRF2/HO-1 signaling pathways. This study is the first to discover the therapeutic effects of HNa on liver damage induced by LPS.

2D Ordered Mesoporous Lamellar Hetero-Nanochannels with Asymmetric Wettability for Controllable Ion Transport.

Heterogeneous membranes play a crucial role in osmotic energy conversion by effectively reducing concentration polarization. However, most heterogeneous membranes mitigate concentration polarization through an asymmetric charge distribution, resulting in compromised ion selectivity. Herein, hetero-nanochannels with asymmetric wettability composed of 2D mesoporous carbon and graphene oxide are constructed. The asymmetric wettability of the membrane endows it with the ability to suppress the concentration polarization without degrading the ion selectivity, as well as achieving a diode-like ion transport feature. As a result, enhanced osmotic energy harvesting is achieved with a power density of 6.41 W m-2 . This represents a substantial enhancement of 102.80-137.85% when compared to homogeneous 2D membranes, surpassing the performance of the majority of reported 2D membranes. Importantly, the membrane can be further used for high-performance ionic power harvesting by regulating ion transport, exceeding previously reported data by 89.1%.

Genome-wide analysis of ALDH gene family in jujube and identification of ZjALDH3F3 for its important role in high-temperature tolerance.

Aldehyde dehydrogenases (ALDHs) are NAD(P)-dependent enzymes that oxidize aliphatic and aromatic aldehydes. They play crucial roles in various biological processes and plant responses to stress. The impact of high temperatures on jujube quality and yield has been well documented. Nevertheless, the involvement of ALDHs in the response to heat stress remains poorly understood. This study aimed to identify ZjALDHs in the jujube genome (Ziziphus jujuba var. spinosa) and conducted in silico analyses. Phylogenetic analyses indicated that ALDHs in plants, including jujube, can be divided into ten families, and members from the same family share conserved gene and protein structures. Quantitative real-time PCR (qRT-PCR) and ß-glucuronidase (GUS) histochemical staining were used to analyze the expression patterns of ZjALDHs in response to elevated temperatures. We identified a ZjALDH (ZjALDH3F3) gene displaying a significant upregulation and down-regulation, respectively in heat-resistant (HR) and heat-sensitive (HS) jujube in response to heat treatments. Such specific responses are probably attributed to the different heat-responsive cis-elements of ZjALDH3F3 in HR and HS jujubes. ZjALDH3F3 over-expressed in tobacco increased heat tolerance, as evidenced by the reduced accumulation of reactive oxygen species (ROS) and elevated activity of antioxidant enzymes. The qRT-PCR results indicated that the expression of antioxidant enzymes, abscisic acid (ABA), and stress-responsive genes was enhanced in transgenic tobacco. This study sheds novel light on the function of ZjALDHs in heat resistance of jujube.

Site-Selective Superassembly of a Multilevel Asymmetric Nanomotor with Wavelength-Modulated Propulsion Mechanisms.

Micro-/nanomotors with advanced motion manipulation have recently received mounting interest; however, research focusing on the motion regulation strategies is still limited, as the simple construction and composition of micro-/nanomotors restrict the functionality. Herein, a multifunctional TiO2-SiO2-mesoporous carbon nanomotor is synthesized via an interfacial superassembly strategy. This nanomotor shows an asymmetric matchstick-like structure, with a head composed of TiO2 and a tail composed of SiO2. Mesoporous carbon is selectively grown on the surface of TiO2 through surface-charge-mediated assembly. The spatially anisotropic distribution of the photocatalytic TiO2 domain and photothermal carbon domain enables multichannel control of the motion, where the speed can be regulated by energy input and the directionality can be regulated by wavelength. Upon UV irradiation, the nanomotor exhibits a head-leading self-diffusiophoretic motion, while upon NIR irradiation, the nanomotor exhibits a tail-leading self-thermophoretic motion. As a proof-of-concept, this mechanism-switchable nanomotor is employed in wavelength-regulated targeted cargo delivery on a microfluidic chip. From an applied point of view, this nanomotor holds potential in biomedical applications such as active drug delivery and phototherapy. From a fundamental point of view, this research can provide insight into the relationship between the nanostructures, propulsion mechanisms, and motion performance.

Sodium humate alleviates LPS-induced intestinal barrier injury by improving intestinal immune function and regulating gut microbiota.

Sodium humate (HNa), known for its abundant functional active groups, is extensively utilized in food dietary supplements due to its versatile properties. Furthermore, HNa possesses notable anti-inflammatory, antioxidant, and anti-diarrheal properties. This research endeavor aimed to elucidate the protective effects of HNa against intestinal barrier injury induced by lipopolysaccharide (LPS). The findings of this study demonstrated that pretreatment with HNa effectively mitigated intestinal barrier injury in the jejunum. HNa exhibited inhibitory effects on the activation of the NLRP3 inflammasome and the production of inflammatory factors within the intestine. HNa supplementation also contributed to the upregulation of mucin and tight junctions (TJs) expression, consequently enhancing the integrity of the intestinal barrier. Notably, our investigation revealed that HNa shared comparable efficacy with the TLR4 inhibitor TAK-242 in inhibiting the TLR4/NFκB signaling pathway. Furthermore, an in-depth analysis of the gut microbiota demonstrated that HNa exerted a regulatory influence on LPS-induced microflora disturbance. In conclusion, these findings collectively indicate that HNa mitigates LPS-induced mucosal damage in the jejunum and preserves the integrity of the intestinal barrier by modulating intestinal immune function and regulating gut microbiota.

Integrative multilevel exploration of the mechanism by which Er-Zhi-Wan alleviates the Parkinson's disease (PD)-like phenotype in the MPTP-induced PD mouse model.

The neuroprotective effects of Er-Zhi-Wan (EZW), a well-known traditional Chinese formulation, in MPTP-induced Parkinson's disease (PD) models are poorly understood and require evaluation. A model of PD induced by MPTP was used to evaluate the neuroprotective effects of EZW in mice. The underlying pharmacological mechanisms of EZW for the prevention and treatment of PD were then explored using a combination of multilevel databases, network pharmacology, biological experiments, and LCMS/MS. In vivo data showed that pretreatment with EZW can be neuroprotective against MPTP-induced motor dysfunction and can effectively rescue dopaminergic neurons from MPTP-induced degeneration in mice. Furthermore, data from combined multilevel databases and network pharmacology analysis strategies suggested that the neuroprotective activity of EZW in the treatment of PD is mediated by a complicated multicomponent, multitarget network. Genes such as Grm2, Grm5, Drd2, and Grik2 were identified as important therapeutic targets. Subsequent experimental validation showed that EZW can broadly regulate the mRNA levels of these receptor genes as well as BDNF, and consequently increase the phosphorylation levels of CREB to stimulate CREB signaling. These targets and signaling systems may be responsible for the reversal of neuronal death by EZW after MPTP exposure. The LC-MS/MS results also identified a wide range of chemical components of EZW, including at least 53 precise compounds, further demonstrating the complexity of the network in which EZW exerts its neuroprotective activity. Our work provides evidence for the mechanism of EZW in MPTP-PD models and supports the neuroprotective function of EZW in neurodegenerative diseases.

Interfacial Super-Assembly of Intertwined Nanofibers toward Hybrid Nanochannels for Synergistic Salinity Gradient Power Conversion.

Capturing the abundant salinity gradient power into electric power by nanofluidic systems has attracted increasing attention and has shown huge potential to alleviate the energy crisis and environmental pollution problems. However, not only the imbalance between permeability and selectivity but also the poor stability and high cost of traditional membranes limit their scale-up realistic applications. Here, intertwined "soft-hard" nanofibers/tubes are densely super-assembled on the surface of anodic aluminum oxide (AAO) to construct a heterogeneous nanochannel membrane, which exhibits smart ion transport and improved salinity gradient power conversion. In this process, one-dimensional (1D) "soft" TEMPO-oxidized cellulose nanofibers (CNFs) are wrapped around "hard" carbon nanotubes (CNTs) to form three-dimensional (3D) dense nanochannel networks, subsequently forming a CNF-CNT/AAO hybrid membrane. The 3D nanochannel networks constructed by this intertwined "soft-hard" nanofiber/tube method can significantly enhance the membrane stability while maintaining the ion selectivity and permeability. Furthermore, benefiting from the asymmetric structure and charge polarity, the hybrid nanofluidic membrane displays a low membrane inner resistance, directional ionic rectification characteristics, outstanding cation selectivity, and excellent salinity gradient power conversion performance with an output power density of 3.3 W/m2. Besides, a pH sensitive property of the hybrid membrane is exhibited, and a higher power density of 4.2 W/m2 can be achieved at a pH of 11, which is approximately 2 times more compared to that of pure 1D nanomaterial based homogeneous membranes. These results indicate that this interfacial super-assembly strategy can provide a way for large-scale production of nanofluidic devices for various fields including salinity gradient energy harvesting.

Dual-Functional Super-Assembled Mesoporous Carbon-Titania/AAO Hetero-Channels for Bidirectionally Photo-Regulated Ion Transport.

Photo-regulated nanofluidic devices have attracted great attention in recent years due to their adjustable ion transport in real time. However, most of the photo-responsive nanofluidic devices can only adjust the ionic current unidirectionally, and cannot simultaneously increase or decrease the current signal intelligently by one device. Herein, a mesoporous carbon-titania/ anodized aluminum hetero-channels (MCT/AAO) is constructed by super-assembly strategy, which exhibits dual-function of cation selectivity and photo response. The polymer and TiO2 nanocrystals jointly build the MCT framework. Polymer framework with abundant negatively charged sites endows MCT/AAO with excellent cation selectivity, and TiO2 nanocrystals are responsible for the photo-regulated ion transport. High photo current densities of 1.8 mA m-2 (increase) and 1.2 mA m-2 (decrease) are realized by MCT/AAO benefiting from the ordered hetero-channels. Significantly, MCT/AAO can also achieve the bidirectionally adjustable osmotic energy by alternating the configurations of concentration gradient. Theoretical and experimental results reveal that the superior photo-generated potential is responsible for the bidirectionally adjustable ion transport. Consequently, MCT/AAO performs the function of harvesting ionic energy from the equilibrium electrolyte solution, which greatly expands its practical application field. This work provides a new strategy in constructing dual-functional hetero-channels toward bidirectionally photo-regulated ionic transport and energy harvesting.

Sodium Humate-Derived Gut Microbiota Ameliorates Intestinal Dysfunction Induced by Salmonella Typhimurium in Mice.

Salmonella is a foodborne pathogen that is one of the main causes of gastroenteric disease in humans and animals. As a natural organic substance, sodium humate (HNa) possesses antibacterial, antidiarrheal, and anti-inflammatory properties. However, it is unclear whether the HNa and HNa-derived microbiota exert alleviative effects on Salmonella enterica serovar Typhimurium-induced enteritis. We found that treatment with HNa disrupted the cell wall of S. Typhimurium and decreased the virulence gene expression. Next, we explored the effect of HNa presupplementation on S. Typhimurium-induced murine enteritis. The results revealed that HNa ameliorated intestinal pathological damage. In addition, we observed that presupplementation with HNa enhanced intestinal barrier function via modulating gut microbiota, downregulating toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3) signaling pathways, regulating intestinal mucosal immunity, and enhancing tight junction protein expression. To further validate the effect of HNa-derived microbiota on S. Typhimurium-induced enteritis, we performed fecal microbiota transplantation and found that HNa-derived microbiota also alleviated S. Typhimurium-induced intestinal damage. It is noteworthy that both HNa and HNa-derived microbiota improved the liver injury caused by S. Typhimurium infection. Collectively, this is the first study to confirm that HNa could alleviate S. Typhimurium-induced enteritis in a gut microbiota-dependent manner. This study provides a new perspective on HNa as a potential drug to prevent and treat salmonellosis. IMPORTANCE Salmonella Typhimurium is an important zoonotic pathogen, widely distributed in nature. S. Typhimurium is one of the leading causes of foodborne illnesses worldwide, and more than 350,000 people died from Salmonella infection each year, which poses a substantial risk to public health and causes a considerable economic loss. Here, we found that the S. Typhimurium infection caused severe intestinal and liver damage. In addition, we first found that sodium humate (HNa) and HNa-derived gut microbiota can alleviate S. Typhimurium infection-induced intestinal damage. These findings extend the knowledge about the public health risk and pathogenic mechanisms of S. Typhimurium.

Cytokinin-inducible response regulator SlRR6 controls plant height through gibberellin and auxin pathways in tomato.

Plant height is a key agronomic trait regulated by several phytohormones such as gibberellins (GAs) and auxin. However, little is known about how cytokinin (CK) participates in this process. Here, we report that SlRR6, a type-A response regulator in the CK signaling pathway, positively regulates plant height in tomato. SlRR6 was induced by exogenous kinetin and GA3, but inhibited by indole-3-acetic acid (IAA). Knock out of SlRR6 reduced tomato plant height through shortening internode length, while overexpression of SlRR6 caused taller plants due to increased internode number. Cytological observation of longitudinal stems showed that both knock out and overexpression of SlRR6 generated larger cells, but significantly reduced cell numbers in each internode. Further studies demonstrated that overexpression of SlRR6 enhanced GA accumulation and lowered IAA content, along with expression changes in GA- and IAA-related genes. Exogenous paclobutrazol and IAA treatments restored the increased plant height phenotype in SlRR6-overexpressing lines. Yeast two-hybrid, bimolecular fluorescence complementation, and co-immunoprecipitation assays showed that SlRR6 interacts with a small auxin up RNA protein, SlSAUR58. Moreover, SlSAUR58-overexpressing plants were dwarf with decreased internode length. Overall, our findings establish SlRR6 as a vital component in the CK signaling, GA, and IAA regulatory network that controls plant height.

Paricalcitol Ameliorates Acute Kidney Injury in Mice by Suppressing Oxidative Stress and Inflammation via Nrf2/HO-1 Signaling.

Effective and targeted prevention and treatment methods for acute kidney injury (AKI), a common clinical complication, still needs to be explored. Paricalcitol is a biologically active chemical that binds to vitamin D receptors in the body to exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanism of the effect of paricalcitol on AKI remains unclear. The current study uses a paricalcitol pretreatment with a mouse AKI model induced by cisplatin to detect changes in renal function, pathology and ultrastructure. Results showed that paricalcitol significantly improved renal function in mice and reduced inflammatory cell infiltration and mitochondrial damage in renal tissue. Furthermore, paricalcitol markedly suppressed reactive oxygen species and malondialdehyde levels in the kidneys of AKI mice and increased the levels of glutathione, superoxide dismutase, Catalase and total anti-oxidant capacity. In addition, we detected renal necrosis and inflammation-related proteins in AKI mice by immunofluorescence and Western blot, and found that their levels were markedly decreased after paricalcitol pretreatment. Moreover, paricalcitol promotes nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus and activates the Nrf2/heme oxygenase-1 (HO-1) signaling pathway; while HO-1 is inhibited, the protective effect of paricalcitol on the kidney is attenuated. In conclusion, paricalcitol exerts a renoprotective effect by decreasing renal oxidative injury and inflammation through Nrf2/HO-1 signaling, providing a new insight into AKI prevention.

In Situ Interfacial Super-Assembly of Nanobiohybrids through Plant for Food-Grade Oral Medicine.

Developing a next-generation oral drug delivery system with enhanced efficacy and limited side effects is highly desired for refractory diseases treatment such as colitis. The bioinspired assembly of drugs within food-grade plants highlights its potential value of this unique hybrid material. Herein, we report the preparation of drug-encapsulated vegetable nanobiohybrid superassembled frameworks as an oral food-grade drug delivery system (SAF-FGDD). The in situ superassembly of SAF-FGDD driven by natural transpiration from living plants is carried out through a sustainable and low-carbon manner, allowing for the assembly of distinct precursors inside edible living plants. As an example, mesalazine, an anti-inflammatory drug, is encapsulated in the frameworks for colitis treatment. The cell activity and feeding experiments of zebrafish and mice demonstrate the excellent efficacy of this SAF-FGDD. Compared with those of the control groups, the disease activity index scores and histological scores of the SAF-FGDD group were significantly decreased by 80% and 98%, respectively. The improved performance is attributed to the biocompatibility and protective effect of SAF-FGDD, allowing for abundant mesalazine to be released and act at the site of the intestine during the process of food digestion. In combination with mature soilless cultivation technology, plant-based organisms with natural structure-forming abilities possess broad commercial prospects in large-scale production of various food-grade functional materials.

Engineering 2D Aligned Nanowires Assembled Porous Hetero-Membrane for Smart Ion Transport.

Engineering 2D nanosheets with well-defined porous structures and their assembled heterostructure membrane is a promising method to improve osmotic energy conversion. However, it is still a great challenge to directly fabricate 2D nanosheets with regular parallel nanochannels in aqueous media. Here, the desired functional nanosheets and heterostructure membrane device are successfully prepared through a simple interfacial assembly strategy. In this method, monolayer cylindrical monomicelles closely arrange and assemble on the surfaces of graphene oxide, and the resulting nanosheets with monolayered aligned nanowire polymer arrays parallel to the substrate surfaces are then obtained. Subsequently, a heterostructured membrane is constructed by assembling these 2D nanosheets on macroporous alumina. The nanofluidic membrane device with asymmetric geometry and charge polarity exhibits smart ion transport properties, and the output osmotic power density is ≈1.22 and 1.63 times over the reported pure 2D graphene oxide and biomass-derived membranes, respectively. In addition, theoretical calculations are carried out to reveal the mechanisms for ion selectivity and salinity gradient energy conversion. This monolayered interfacial assembly approach can open up new avenues for the synthesis of functional porous low-dimensional nanomaterials and membrane devices, and expand the palette of materials selection for many applications.

A Novel Design Concept of Cemented Paste Backfill (CPB) Materials: Biobjective Optimization Approach by Applying an Evolved Random Forest Model.

For cemented paste backfill (CPB), uniaxial compressive strength (UCS) is the key to ensuring the safety of stope construction, and its cost is an important part of the mining cost. However, there are a lack of design methods based on UCS and cost optimization. To address such issues, this study proposes a biobjective optimization approach by applying a novel evolved random forest (RF) model. First, the evolved RF model, based on the beetle search algorithm (BAS), was constructed to predict the UCS of CPB. The consistency between the predicted value and the actual value is high, which proves that the hybrid machine learning model has a good effect on the prediction of the UCS of CPB. Then, considering the linear relationship between the costs and the components of CPB, a mathematical model of the cost is constructed. Finally, based on the weighted sum method, the biobjective optimization process of the UCS and cost of CPB is conducted; the Pareto front optimal solutions of UCS and the cost of CPB can be obtained by the sort of solution set. When the UCS or the cost of CPB is constant, the Pareto front optimal solutions can always have a lower cost or a higher UCS compared with the actual dataset, which proves that the biobjective optimization approach has a good effect.

Mixture Optimization of Cementitious Materials Using Machine Learning and Metaheuristic Algorithms: State of the Art and Future Prospects.

The hybrid optimization of modern cementitious materials requires concrete to meet many competing objectives (e.g., mechanical properties, cost, workability, environmental requirements, and durability). This paper reviews the current literature on optimizing mixing ratios using machine learning and metaheuristic optimization algorithms based on past studies on varying methods. In this review, we first discuss the conventional methods for mixing optimization of cementitious materials. Then, the problem expression of hybrid optimization is discussed, including decision variables, constraints, machine learning algorithms for modeling objectives, and metaheuristic optimization algorithms for searching the best mixture ratio. Finally, we explore the development prospects of this field, including, expanding the database by combining field data, considering more influencing variables, and considering more competitive targets in the production of functional cemented materials. In addition, to overcome the limitation of the swarm intelligence-based multi-objective optimization (MOO) algorithm in hybrid optimization, this paper proposes a new MOO algorithm based on individual intelligence (multi-objective beetle antenna search algorithm). The development of computationally efficient robust MOO models will continue to make progress in the field of hybrid optimization. This review is adapted for engineers and researchers who want to optimize the mixture proportions of cementitious materials using machine learning and metaheuristic algorithms.

Esophageal low-grade intraepithelial neoplasia overlying multiple leiomyomas: A case report and review of the literature.

Background: Esophageal leiomyoma is the most common benign submucosal mesenchymal tumor. Esophageal intraepithelial neoplasia includes low-grade and high-grade intraepithelial neoplasia. The coexistence of epithelial lesions and the subepithelial lesion is rare. We recorded a case of esophageal low-grade intraepithelial neoplasia (LGIN) overlying multiple esophageal leiomyomas and followed with a review of the literature. Case presentation: A 49-year-old female patient came for the treatment of esophageal lesions. The submucosal eminences were observed in the right posterior wall and the left anterior wall of the esophagus by Esophagogastroduodenoscopy (EGD). Additionally, we noticed the mucosa of the right wall with brown background color and the dilated, tortuous vessels by narrow-band imaging (NBI). Then we ensured that the submucosal lesions originated from the esophageal mucosal muscle by endoscopic ultrasonography (EUS) and enhanced CT. Subsequently, the submucosal eminence of the right posterior wall and the overlying mucosal lesion were removed together by endoscopic submucosal dissection (ESD). Postoperative pathological diagnosed esophageal submucosal leiomyoma with focal LGIN. Review EGD showed white scars on the right wall of the upper esophagus three months later, while pathological biopsy showed slight squamous epithelial hyperplasia in the left wall. We decided that the left submucosal lesion can be resected at a selective-time operation, and we continue to follow up as planned. Conclusions: The case of intraepithelial neoplasia overlying the submucosal tumor is rare. Either missed diagnosis or overdiagnosis should be avoided through EGD and pathological biopsy.

Exploring the mechanisms underlying the therapeutic effect of the Radix Bupleuri-Rhizoma Cyperi herb pair on hepatocellular carcinoma using multilevel data integration and molecular docking.

Traditional Chinese medicine (TCM) is a promising and effective treatment for cancer with minimal side effects through a multi-active ingredient multitarget network. Radix Bupleuri and Rhizoma Cyperi are listed as herbs dispersing stagnated liver Qi in China. They have been used clinically to treat liver diseases for many years and recent pharmacological studies have shown that they inhibit the proliferation of hepatocellular carcinoma (HCC). However, the pharmacological mechanisms, potential targets, and clinical value of the Radix Bupleuri-Rhizoma Cyperi herb pair (CXP) for suppressing HCC growth have not been fully elucidated. We identified 44 CXP targets involved in the treatment of HCC using the GEO dataset and HERB database. An analysis of the Traditional Chinese Medicine System Pharmacology Database (TCMSP) showed that CXP exerts synergistic effects through 4 active ingredients, including quercetin, stigmasterol, isorhamnetin, and kaempferol. GO and KEGG analyses revealed that CXP mainly regulates HCC progression through metabolic pathways, the p53 signaling pathway, and the cell cycle. Additionally, we applied The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) database to perform the expression patterns, clinical features, and prognosis of 6 genes (CCNB1, CDK1, CDK4, MYC, CDKN2A, and CHEK1) in cell cycle pathways to reveal that CXP suppresses HCC clinical therapeutic value. Moreover, based on molecular docking, we further verified that CXP exerts its anti-HCC activity through the interaction of multiple active components with cell cycle-related genes. We systematically revealed the potential pharmacological mechanisms and targets of CXP in HCC using multilevel data integration and molecular docking strategies.