[Retracted] Emodin alleviates gemcitabine resistance in pancreatic cancer by inhibiting MDR1/P­glycoprotein and MRPs expression.

[This retracts the article DOI: 10.3892/ol.2020.12030.].

Understanding the relationship between pore size, surface charge density, and Cu2+ adsorption in mesoporous silica.

This research delved into the influence of mesoporous silica's surface charge density on the adsorption of Cu2+. The synthesis of mesoporous silica employed the hydrothermal method, with pore size controlled by varying the length of trimethylammonium bromide (CnTAB, n = 12, 14, 16) chains. Gas adsorption techniques and transmission electron microscopy characterized the mesoporous silica structure. Surface charge densities of the mesoporous silica were determined through potentiometric titration, while surface hydroxyl densities were assessed using the thermogravimetric method. Subsequently, batch adsorption experiments were conducted to study the adsorption of Cu2+ in mesoporous silica, and the process was comprehensively analyzed using Atomic absorption spectrometry (AAS), Fourier transform infrared (FTIR), and L3 edge X-ray absorption near edge structure (XANES). The research findings suggest a positive correlation between the pore size of mesoporous silica, its surface charge density, and the adsorption capacity for Cu2+. More specifically, as the pore size increases within the 3-4.1 nm range, the surface charge density and the adsorption capacity for Cu2+ also increase. Our findings provide valuable insights into the relationship between the physicochemical properties of mesoporous silica and the adsorption behavior of Cu2+, offering potential applications in areas such as environmental remediation and catalysis.

Machine learning-based prediction models affecting the recovery of postoperative bowel function for patients undergoing colorectal surgeries.

PURPOSE: The debate surrounding factors influencing postoperative flatus and defecation in patients undergoing colorectal resection prompted this study. Our objective was to identify independent risk factors and develop prediction models for postoperative bowel function in patients undergoing colorectal surgeries. METHODS: A retrospective analysis of medical records was conducted for patients who undergoing colorectal surgeries at Peking University People's Hospital from January 2015 to October 2021. Machine learning algorithms were employed to identify risk factors and construct prediction models for the time of the first postoperative flatus and defecation. The prediction models were evaluated using sensitivity, specificity, the Youden index, and the area under the receiver operating characteristic curve (AUC) through logistic regression, random forest, Naïve Bayes, and extreme gradient boosting algorithms. RESULTS: The study included 1358 patients for postoperative flatus timing analysis and 1430 patients for postoperative defecation timing analysis between January 2015 and December 2020 as part of the training phase. Additionally, a validation set comprised 200 patients who undergoing colorectal surgeries from January to October 2021. The logistic regression prediction model exhibited the highest AUC (0.78) for predicting the timing of the first postoperative flatus. Identified independent risk factors influencing the time of first postoperative flatus were Age (p < 0.01), oral laxatives for bowel preparation (p = 0.01), probiotics (p = 0.02), oral antibiotics for bowel preparation (p = 0.02), duration of operation (p = 0.02), postoperative fortified antibiotics (p = 0.02), and time of first postoperative feeding (p < 0.01). Furthermore, logistic regression achieved an AUC of 0.72 for predicting the time of first postoperative defecation, with age (p < 0.01), oral antibiotics for bowel preparation (p = 0.01), probiotics (p = 0.01), and time of first postoperative feeding (p < 0.01) identified as independent risk factors. CONCLUSIONS: The study suggests that he use of probiotics and early recovery of diet may enhance the recovery of bowel function in patients undergoing colorectal surgeries. Among the various analytical methods used, logistic regression emerged as the most effective approach for predicting the timing of the first postoperative flatus and defecation in this patient population.

Dual-Responsive Nanomedicine Activates Programmed Antitumor Immunity through Targeting Lymphatic System.

Effective antitumor immunotherapy depends on evoking a cascade of cancer-immune cycles with lymph nodes (LNs) as the initial sites for activating antitumor immunity, making drug administration through the lymphatic system highly attractive. Here, we describe a nanomedicine with dual responsiveness to pH and enzyme for a programmed activation of antitumor immune through the lymphatic system. The proposed nanomedicine can release the STING agonist diABZI-C2-NH2 in the LNs' acidic environment to activate dendritic cells (DCs) and T cells. Then, the remaining nanomedicine hitchhikes on the activated T cells (PD-1+ T cells) through binding to PD-1, resulting in an effective delivery into tumor tissues owing to the tumor-homing capacity of PD-1+ T cells. The enzyme matrix metalloproteinase-2 (MMP-2) being enriched in tumor tissue triggers the release of PD-1 antibody (aPD-1) which exerts immune checkpoint blockade (ICB) therapy. Eventually, the nanomedicine delivers a DNA methylation inhibitor GSK-3484862 (GSK) into tumor cells, and then the latter combines with granzyme B (GZMB) to trigger tumor cell pyroptosis. Consequently, the pyroptotic tumor cells induce robust immunogenic cell death (ICD) enhancing the DCs maturation and initiating the cascading antitumor immune response. Study on a 4T1 breast tumor mouse model demonstrates the prominent antitumor therapeutic outcome of this nanomedicine through creating a positive feedback loop of cancer-immunity cycles including immune activation in LNs, T cell-mediated drug delivery, ICB therapy, and tumor cell pyroptosis-featured ICD.

Urine-derived stem cells: Promising advancements and applications in regenerative medicine and beyond.

Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.

Stepwisely Assembled Multicomponent Fiber with High Water Content and Superior Mechanical Properties for Artificial Ligament.

The ligament, which connects bones at the joints, has both high water content and excellent mechanical properties in living organisms. However, it is still challenging to fabricate fibrous materials that possess high water content and ligament-like mechanical characteristics simultaneously. Herein, the design and preparation of a ligament-mimicking multicomponent fiber is reported through stepwise assembly of polysaccharide, calcium, and dopamine. In simulated body fluid, the resulting fiber has a water content of 40 wt%, while demonstrating strength of ≈120 MPa, a Young's modulus of ≈3 GPa, and a toughness of ≈25 MJ m-3. Additionally, the multicomponent fiber exhibits excellent creep and fatigue resistance, as well as biocompatibility to support cell growth in vitro. These findings suggest that the fiber has potential for engineering high-performance artificial ligament.

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways.

Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration.

Glycogen synthase kinase 3 signaling in neural regeneration in vivo.

Glycogen synthase kinase 3 (GSK3) signaling plays important and broad roles in regulating neural development in vitro and in vivo. Here, we reviewed recent findings of GSK3-regulated axon regeneration in vivo in both the peripheral and central nervous systems and discussed a few controversial findings in the field. Overall, current evidence indicates that GSK3ß signaling serves as an important downstream mediator of the PI3K-AKT pathway to regulate axon regeneration in parallel with the mTORC1 pathway. Specifically, the mTORC1 pathway supports axon regeneration mainly through its role in regulating cap-dependent protein translation, whereas GSK3ß signaling might be involved in regulating N6-methyladenosine (m6A) mRNA methylation-mediated cap-independent protein translation. In addition, GSK3 signaling also plays key roles in reshaping the neuronal transcriptomic landscape during neural regeneration. Finally, we proposed some research directions to further elucidate the molecular mechanisms underlying the regulatory function of GSK3 signaling and discover novel GSK3 signaling-related therapeutic targets. Together, we hope to provide an updated and insightful overview of how GSK3 signaling regulates neural regeneration in vivo.

Interfacial Behaviors of Giant Amphiphilic Molecules Composed of Hydrophobic Isobutyl POSS and Hydrophilic POSS Bearing Carboxylic Acid Groups at the Air-Water Interface.

The behavior of giant amphiphilic molecules at the air-water interface has become a subject of concern to researchers. Small changes in the molecular structure can cause obvious differences in the molecular arrangement and interfacial properties of the monolayer. In this study, we have systematically investigated the interfacial behaviors of the giant amphiphilic molecules with different number of hydrophobic BPOSS blocks and one hydrophilic ACPOSS block ((BPOSS)n-ACPOSS (n = 1-5)) at the air-water interface by the surface pressure-area (π-A) isotherm, Brewster angle microscopy (BAM), compression modulus measurement, and hysteresis measurement. We found that both the number of BPOSS blocks and the compression rate can significantly influence the interfacial behaviors of giant molecules. The π-A isotherms of giant molecules (BPOSS)n-ACPOSS (n = 2-5) exhibit a "cusp" phenomenon which can be attributed to the transition from monolayer to multilayer. However, the cusp is dramatically different from the "collapse" of the monolayer studied in other molecular systems, which is highly dependent on the compression rate of the monolayer. In addition, the compression modulus and hysteresis measurements reveal that the number of BPOSS blocks of (BPOSS)n-ACPOSS plays an important role in the static elasticity, stability, and reversibility of the Langmuir films.

X chromosome encoded histone demethylase UTX regulates mammalian axon regeneration via microRNA-124.

Neurons in the mammalian central nervous system (CNS) gradually lose their intrinsic regeneration capacity during maturation mainly because of altered transcription profile. Recent studies have made great progress by identifying genes that can be manipulated to enhance CNS regeneration. However, as a complex process involving many genes and signaling networks, it is of great importance to deciphering the underlying neuronal chromatin and transcriptomic landscape coordinating CNS regeneration. Here we identify UTX, an X-chromosome associated gene encoding a histone demethylase, as a novel regulator of mammalian neural regeneration. We demonstrate that UTX acts as a repressor of spontaneous axon regeneration in the peripheral nerve system (PNS). In the CNS, either knocking out or pharmacological inhibiting UTX in retinal ganglion cells (RGCs) leads to significantly enhanced neuronal survival and optic nerve regeneration. RNA-seq profiling revealed that deleting UTX switches the RGC transcriptomics into a developmental-like state. Moreover, microRNA-124, one of the most abundant microRNAs in mature neurons, is identified as a downstream target of UTX and blocking endogenous microRNA124-5p results in robust optic nerve regeneration. These findings revealed a novel histone modification-microRNA epigenetic signaling network orchestrating transcriptomic landscape supporting CNS neural regeneration.

Polymer Complex Multilayers for Drug Delivery and Medical Devices.

Polymer complex multilayers (PCMs) can be engineered into various structures with tunable properties via layer-by-layer (LBL) assembly driven by noncovalent forces. Due to their ease of preparation, capability of integrating multiple functional components, and excellent substrate compliance, biocompatible PCMs as coating materials or individual entities have attracted extensive attention in biomedical applications. This Spotlight on Applications presents recent progress on PCMs applied for drug delivery and medical devices. We provide several examples to address the importance of using PCM platforms to achieve controlled drug delivery including stimuli-triggered release, sustained release, and spatiotemporal sequential release. The effects of PCM coatings on the bioresponse regulation and performance enhancement of implantable devices are also highlighted. Moreover, the design and fabrication of flexible electrical and optical elements modified with LBL PCMs have been discussed, which demonstrates the great potential to advance emerging wearable devices for disease monitoring and health management.

Genomic insight into domestication of rubber tree.

Understanding the genetic basis of rubber tree (Hevea brasiliensis) domestication is crucial for further improving natural rubber production to meet its increasing demand worldwide. Here we provide a high-quality H. brasiliensis genome assembly (1.58 Gb, contig N50 of 11.21 megabases), present a map of genome variations by resequencing 335 accessions and reveal domestication-related molecular signals and a major domestication trait, the higher number of laticifer rings. We further show that HbPSK5, encoding the small-peptide hormone phytosulfokine (PSK), is a key domestication gene and closely correlated with the major domestication trait. The transcriptional activation of HbPSK5 by myelocytomatosis (MYC) members links PSK signaling to jasmonates in regulating the laticifer differentiation in rubber tree. Heterologous overexpression of HbPSK5 in Russian dandelion (Taraxacum kok-saghyz) can increase rubber content by promoting laticifer formation. Our results provide an insight into target genes for improving rubber tree and accelerating the domestication of other rubber-producing plants.

[Network Meta-analysis of oral Chinese patent medicines in treatment of acute exacerbation of chronic obstructive pulmonary disease].

This study aimed to evaluate the effectiveness and safety of eight oral Chinese patent medicines in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) by network Meta-analysis. Randomized controlled trial(RCT) on the treatment of AECOPD with eight oral Chinese patent medicines was retrieved from databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library from database inception to August 6, 2022. The information was extracted from the included literature and the quality of the included studies was evaluated using the Cochrane risk of bias assessment tool. The data were analyzed using Stata SE 15.1 and ADDIS 1.16.8 software. Finally, 53 RCTs were included, with 5 289 patients involved, including 2 652 patients in the experimental group and 2 637 patients in the control group. Network Meta-analysis showed that Lianhua Qingwen Capsules+conventional western medicine were optimal in improving clinical effective rate, Shufeng Jiedu Capsules+conventional western medicine in improving FEV1/FVC, Qingqi Huatan Pills+conventional western medicine in improving FEV1%pred, Feilike Mixture(Capsules)+conventional western medicine in improving PaO_2, Lianhua Qingwen Capsules+conventional western medicine in reducing PaCO_2, and Qingqi Huatan Pills+conventional western medicine in reducing C-reactive protein(CRP). In terms of safety, most of them were gastrointestinal symptoms, and no serious adverse reactions were reported. When the clinical effective rate was taken as the comprehensive index of efficacy evaluation, Lianhua Qingwen Capsules+conventional western medicine were the most likely to be the best treatment for AECOPD. There are some limitations in the conclusion of this study. It only provides references for clinical medication.

Construction of pH-Sensitive Nanovaccines Encapsulating Tumor Cell Lysates and Immune Adjuvants for Breast Cancer Therapy.

The current immunotherapy strategies for triple negative breast cancer (TNBC) are greatly limited due to the immunosuppressive tumor microenvironment (TME). Immunization with cancer vaccines composed of tumor cell lysates (TCL) can induce an effective antitumor immune response. However, this approach also has the disadvantages of inefficient antigen delivery to the tumor tissues and the limited immune response elicited by single-antigen vaccines. To overcome these limitations, a pH-sensitive nanocalcium carbonate (CaCO3 ) carrier loaded with TCL and immune adjuvant CpG (CpG oligodeoxynucleotide 1826) is herein constructed for TNBC immunotherapy. This tailor-made nanovaccine, termed CaCO3 @TCL/CpG, not only neutralizes the acidic TME through the consumption of lactate by CaCO3 , which increases the proportion of the M1/M2 macrophages and promotes infiltration of effector immune cells but also activates the dendritic cells in the tumor tissues and recruits cytotoxic T cells to further kill the tumor cells. In vivo fluorescence imaging study shows that the pegylated nanovaccine could stay longer in the blood circulation and extravasate preferentially into tumor site. Besides, the nanovaccine exhibits high cytotoxicity in 4T1 cells and significantly inhibits tumor growth of tumor-bearing mice. Overall, this pH-sensitive nanovaccine is a promising nanoplatform for enhanced immunotherapy of TNBC.

Ambient Environment Adaptive Elastomer Constructed by Microphase Separation and Segment Complexation of Triblock Copolymers.

Elastomers with environmental adaption have attracted considerable attention for advanced applications in various areas. Here, we fabricate an ambient environment adaptive elastomer by assembling triblock copolymers polystyrene-b-poly(acrylic acid)-b-polystyrene (SAS) and polystyrene-b-poly(ethylene oxide)-b-polystyrene (SES). Owing to the microphase separation of triblock polymers and hydrogen-bonding complexation of their middle segments, the SAS/SES complex presents dichotomy of vitrified hard PS domains and soft PAA/PEO domains, which presents major relaxation transition in the temperature zone 10-30 °C and relative humidity (RH) 40-60%. The SAS/SES elastomer presents quick adaption to the ambient environment change with temperature and humidity coupling. Moreover, after a loading-unloading cycle training, the SAS/SES elastomer exhibits domain orientation, low energy dissipation, high recovery ratio, and distinct strain stiffening compared with the pristine complex. The SAS/SES elastomer has potential to be used as a sensing and adaption component for complicated intelligent systems.

Nanodrug Inducing Autophagy Inhibition and Mitochondria Dysfunction for Potentiating Tumor Photo-Immunotherapy.

Anticancer immunotherapy is hampered by the poor tumor immunogenicity and immunosuppressive tumor microenvironment (TME). Herein, a liposome nanodrug co-encapsulating doxycycline hydrochloride (Doxy) and chlorin e6 (Ce6) to simultaneously induce autophagy inhibition and mitochondria dysfunction for potentiating tumor photo-immunotherapy is developed. Under near infrared laser irradiation, Ce6 generates cytotoxic reactive oxygen species (ROS) and elicits robust photodynamic therapy (PDT)-induced immunogenic cell death (ICD) for immunosuppressive TME remodeling. In addition, Doxy induced mitochondria dysfunction, which increases ROS generation and enhances PDT to exert more potent killing effect and more powerful ICD. Meanwhile, Doxy increases MHC-I expression on tumor cells surface by efficient autophagy inhibition, leading to more efficient antigen presentation and CTLs recognition to increase tumor immunogenicity. The nanodrugs elicit remarkable antitumor therapy by combining Ce6-mediated PDT and Doxy-induced autophagy inhibition and mitochondria dysfunction. The developed nanodrugs represent a highly efficient strategy for improving cancer immunotherapy.

Leveraging Macromolecular Isomerism for Phase Complexity in Janus Nanograins.

It remains intriguing whether macromolecular isomerism, along with competing molecular interactions, could be leveraged to create unconventional phase structures and generate considerable phase complexity in soft matter. Herein, we report the synthesis, assembly, and phase behaviors of a series of precisely defined regioisomeric Janus nanograins with distinct core symmetry. They are named B2DB2 where B stands for iso-butyl-functionalized polyhedral oligomeric silsesquioxanes (POSS) and D stands for dihydroxyl-functionalized POSS. While BPOSS prefers crystallization with a flat interface, DPOSS prefers to phase-separate from BPOSS. In solution, they form 2D crystals owing to strong BPOSS crystallization. In bulk, the subtle competition between crystallization and phase separation is strongly influenced by the core symmetry, leading to distinct phase structures and transition behaviors. The phase complexity was understood based on their symmetry, molecular packing, and free energy profiles. The results demonstrate that regioisomerism could indeed generate profound phase complexity.

Impact of iron/aluminum (hydr)oxide and clay minerals on heteroaggregation and transport of nanoplastics in aquatic environment.

Nanoplastics (NPs) are emerging contaminants in the environment, where the transport and fate of NPs would be greatly affected by interactions between NPs and minerals. In the present study, the interactions of two types of polystyrene nanoplastics (PSNPs), i.e., bare-PSNPs and carboxylated PSNPs-COOH, with iron (hydr)oxides (hematite, goethite, magnetite, and ferrihydrite), aluminum (hydr)oxides (boehmite and gibbsite), and clay minerals (kaolinite, montmorillonite, and illite) were investigated. The positively charged iron/aluminum (hydr)oxide minerals could form heteroaggregates with negatively charged PSNPs. Electrostatic and hydrophobic interaction dominate for the heteroaggregation of bare-PSNPs with iron/aluminum (hydr)oxide minerals, while ligand exchange and electrostatic interaction are involved in the heteroaggregation of PSNPs-COOH with iron/aluminum (hydr)oxides minerals. However, heteroaggregation between PSNPs and negatively charged clay minerals was negligible. Humic acid markedly suppressed such heteroaggregation between PSNPs and minerals due to enhanced electrostatic repulsion, steric hindrance, and competition of surface attachment sites. The heteroaggregation rates of both bare-PSNPs and PSNPs-COOH with hematite decreased with increasing solution pH. Increased ionic strength enhanced the heteroaggregation of PSNPs-COOH but inhibited that of bare-PSNPs. The results of the present study suggested that the heteroaggregation of PSNPs in environments could be strongly affected by minerals, solution pH, humic acid, and ionic strength.

Polymer Complex Fiber: Property, Functionality, and Applications.

Polymer complex fibers (PCFs) are a novel kind of fiber material processed from polymer complexes that are assembled through noncovalent interactions. These can realize the synergy of functional components and miscibility on the molecular level. The dynamic character of noncovalent interactions endows PCFs with remarkable properties, such as reversibility, stimuli responsiveness, self-healing, and recyclability, enabling them to be applied in multidisciplinary fields. The objective of this article is to provide a review of recent progress in the field of PCFs. The classification based on chain interactions will be first introduced followed by highlights of the fabrication technologies and properties of PCFs. The effects of composition and preparation method on fiber properties are also discussed, with some emphasis on utilizing these for rational design. Finally, we carefully summarize recent advanced applications of PCFs in the fields of energy storage and sensors, water treatment, biomedical materials, artificial actuators, and biomimetic platforms. This review is expected to deepen the comprehension of PCF materials and open new avenues for developing PCFs with tailor-made properties for advanced application.

Stretchable Optical Diffuser Constructed by Alternate Procedure of Interfacial Complexation and Thermal Crosslinking.

Stretchable optical diffuser is an indispensable photon management element in wearable display devices. Herein, a novel optical diffuser constructed by interfacial hydrogen bonding complexation of methylcellulose (MC), poly(ethylene oxide) (PEO), and polymer complex nanoparticles (PCNP) on transparent polydimethylsiloxane (PDMS) substrate is proposed. The introduction of PEO can toughen the complex film and endow the coating with stretchability. With proper thermal treatment, the polymer complex can be crosslinked through esterification which shows an improved optical diffusion performance and durability. The optimized film exhibits 92% of transmittance (T), 93% of haze (H), and 73% of elongation. It also presents a desirable optical diffusion effect about 88% of T and 93% of H in the stretching state. Moreover, the resulting complex film shows excellent anti-fatigue capacity which maintains 90% of T and 90% of H after 10 000 stretching cycles. The reported polymer complex film broadens the application of interfacial complexation and demonstrates potential to apply in the integrated wearable optical devices.