GBCdb: RNA expression landscapes and ncRNA-mRNA interactions in gallbladder carcinoma.

Gallbladder carcinoma (GBC), an aggressive malignant tumor of the biliary system, is characterized by high cellular heterogeneity and poor prognosis. Fewer data have been reported in GBC than other common cancer types. Multi-omics data will contribute to the understanding of the molecular mechanisms of cancer, cancer diagnosis and prognosis. Herein, to provide better understanding of the molecular events in GBC pathogenesis, we developed GBCdb ( http://tmliang.cn/gbc/ ), a user-friendly interface for the query and browsing of GBC-associated genes and RNA interaction networks using published multi-omics data, which also included experimentally supported data from different molecular levels. GBCdb will help to elucidate the potential biological roles of different RNAs and allow for the exploration of RNA interactions in GBC. These resources will provide an opportunity for unraveling the potential molecular features of Gallbladder carcinoma.

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR.

Circular RNAs (circRNAs), a class of new endogenous non-coding RNAs (ncRNAs), are closely related to the carcinogenic process and play a critical role in tumor metastasis. CircRNAs can lay the foundation for tumor metastasis via promoting tumor angiogenesis, make tumor cells gain the ability of migration and invasion by regulating epithelial-mesenchymal transition (EMT), interact with immune cells, cytokines, chemokines, and other non-cellular components in the tumor microenvironment, damage the normal immune function or escape the immunosuppressive network, and further promote cell survival and metastasis. Herein, based on the characteristics and biological functions of circRNA, we elaborated on the effect of circRNA via circRNA-associated competing endogenous RNA (ceRNA) network by acting as miRNA/isomiR sponges on tumor angiogenesis, cancer cell migration and invasion, and interaction with the tumor microenvironment (TME), then explored the potential interactions across different RNAs, and finally discussed the potential clinical value and application as a promising biomarker. These results provide a theoretical basis for the further application of metastasis-related circRNAs in cancer treatment. In summary, we briefly summarize the diverse roles of a circRNA-associated ceRNA network in cancer metastasis and the potential clinical application, especially the interaction of circRNA and miRNA/isomiR, which may complicate the RNA regulatory network and which will contribute to a novel insight into circRNA in the future.

Averaging speckle patterns to improve the robustness of compressive multimode fiber imaging against fiber bend.

Fiber bend is a major challenge of multimode fiber (MMF) imaging. More robustness against fiber bend is demonstrated in compressive MMF imaging using mean speckle patterns captured at multiple potential bending configurations beforehand, rather than sticking to single patterns at initial configuration. Experiments demonstrate an overall quality improvement on recovered images than previous work, which is important for robust endoscopic application.

Challenges and recent advances in MOF-based gas separation membranes.

Membrane-based gas separation, characterized by a small footprint, low energy consumption and no pollution, has gained widespread attention as an environmentally friendly alternative to traditional gas separation. Metal-organic-frameworks (MOFs) are considered to be one of the most promising membrane-based gas separation materials because of their large specific surface area and high porosity. One of the hottest studies at the moment is how to utilize the characteristics of MOFs to prepare higher performance gas separation membranes. This paper provides a review of gas separation membranes used in recent years. Firstly, the synthesis methods of MOFs and MOF membranes are briefly introduced. Then, methods to improve the membrane properties of MOFs are described in detail, and include applications of lamellar MOFs, ionic liquid (IL) spin coating, functionalization of MOFs, defect engineering and mixed fillers. In addition, the challenges of MOF-based gas separation membranes are presented, including pore size, environmental disturbances, plasticization, interfacial compatibility, and so on. Finally, based on the current development status of the MOF membranes, the development prospects of MOF gas separation membranes are discussed. It is hoped to provide reliable and complete ideas for researchers to prepare high-performance gas separation membranes in the future.

Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models.

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 µM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.

Systematic analysis of cancer-specific synthetic lethal interactions provides insight into personalized anticancer therapy.

The concept of synthetic lethality has great potential for anticancer therapy as a new strategy to specifically kill cancer cells while sparing normal cells. To further understand the potential molecular interactions and gene characteristics involved in synthetic lethality, we performed a comprehensive analysis of predicted cancer-specific genetic interactions. Many genes were identified as cancer-associated genes that contributed to multiple biological processes and pathways, and the gene features were not random, indicating their potential roles in human carcinogenesis. Some relevant genes detected in multiple cancers were prone to be enriched in specific biological progresses and pathways, especially processes associated with DNA damage, chromosome-related functions and cancer pathways. These findings strongly implicated potential roles for these genes in cancer pathophysiology and functional relationships, as well as applications for future anticancer drug discovery. Further experimental validation indicated that the synthetic lethal interaction of APC and GFER may provide a potential anticancer strategy for patients with APC-mutant colon cancer. These results will contribute to further exploration of synthetic lethal interactions and broader application of the concept of synthetic lethality in anticancer therapeutics.

Design of large-span stick-slip freely switchable hydrogels via dynamic multiscale contact synergy.

Solid matter that can rapidly and reversibly switch between adhesive and non-adhesive states is desired in many technological domains including climbing robotics, actuators, wound dressings, and bioelectronics due to the ability for on-demand attachment and detachment. For most types of smart adhesive materials, however, reversible switching occurs only at narrow scales (nanoscale or microscale), which limits the realization of interchangeable surfaces with distinct adhesive states. Here, we report the design of a switchable adhesive hydrogel via dynamic multiscale contact synergy, termed as DMCS-hydrogel. The hydrogel rapidly switches between slippery (friction ~0.04 N/cm2) and sticky (adhesion ~3 N/cm2) states in the solid-solid contact process, exhibits large span, is switchable and dynamic, and features rapid adhesive switching. The design strategy of this material has wide applications ranging from programmable adhesive materials to intelligent devices.

Molecular Engineering Super-Robust Dry/Wet Adhesive with Strong Interface Bonding and Excellent Mechanical Tolerance.

Despite the fact that synthetic adhesives have achieved great progress, achieving robust dry/wet adhesion under harsh operating environments is still challenging. Herein, inspired from the extraordinary adhesion mechanism of nature mussel protein adhesive, the balanced design concept of co-adhesion and interfacial adhesion is proposed to prepare one kind of novel copolymer adhesive of [poly(dopamine methacrylamide-co-methoxethyl acrylate-co-adamantane-1-carboxylic acid 2-(2-methyl-acryloyloxy)-ethyl ester)] [p(DMA-co-MEA-co-AD)], named as super-robust adhesive (SRAD). The SRAD exhibits ultra-high interface bonding strengths in air (∼7.66 MPa) and underwater (∼2.78 MPa) against an iron substrate. Especially, a greatly tough and stable adhesion strength (∼2.11 MPa) can be achieved after immersing the bonded sample in water for half a year. Furthermore, the SRAD demonstrates surprising wet bonding robustness/tolerance even encountering harsh conditions such as fluid shearing, dynamic loading, and cyclic mechanical fretting. The great advantages of SRAD, such as strong interface bonding, stable wet adhesion underwater, and good mechanical tolerance, makes it demonstrate huge application potential in engineering sealants and underwater adhesion.

Toward a Multifunctional Light-Driven Biomimetic Mudskipper-Like Robot for Various Application Scenarios.

The systematicness, flexibility, and complexity of natural biological organisms are a constant stream of inspiration for researchers. Therefore, mimicking the natural intelligence system to develop microrobotics has attracted broad interests. However, developing a multifunctional device for various application scenarios has great challenges. Herein, we present a bionic multifunctional actuation device─a light-driven mudskipper-like actuator that is composed of a porous silicone elastomer and graphene oxide. The actuator exhibits a reversible and well-integrated response to near-infrared (NIR) light due to the photothermal-induced contractile stress in the actuation film, which promotes generation of cyclical and rapid locomotion upon NIR light being switched on and off, such as bending in air and crawling in liquid. Furthermore, through rational device design and modulation of light, the mechanically versatile device can float and swim controllably following a predesigned route at the liquid/air interface. More interestingly, the actuator can jump from liquid medium to air with an extremely short response time (400 ms), a maximum speed of 2 m s-1, and a height of 14.3 cm under the stimulation of near-infrared light. The present work possesses great potential in the applications of bioinspired actuators in various fields, such as microrobots, sensors, and locomotion.

SLOAD: a comprehensive database of cancer-specific synthetic lethal interactions for precision cancer therapy via multi-omics analysis.

Synthetic lethality has been widely concerned because of its potential role in cancer treatment, which can be harnessed to selectively kill cancer cells via identifying inactive genes in a specific cancer type and further targeting the corresponding synthetic lethal partners. Herein, to obtain cancer-specific synthetic lethal interactions, we aimed to predict genetic interactions via a pan-cancer analysis from multiple molecular levels using random forest and then develop a user-friendly database. First, based on collected public gene pairs with synthetic lethal interactions, candidate gene pairs were analyzed via integrating multi-omics data, mainly including DNA mutation, copy number variation, methylation and mRNA expression data. Then, integrated features were used to predict cancer-specific synthetic lethal interactions using random forest. Finally, SLOAD (http://www.tmliang.cn/SLOAD) was constructed via integrating these findings, which was a user-friendly database for data searching, browsing, downloading and analyzing. These results can provide candidate cancer-specific synthetic lethal interactions, which will contribute to drug designing in cancer treatment that can promote therapy strategies based on the principle of synthetic lethality. Database URL http://www.tmliang.cn/SLOAD/.

Characterization of Immune-Based Molecular Subtypes and Prognostic Model in Prostate Adenocarcinoma.

Prostate adenocarcinoma (PRAD), also named prostate cancer, the most common visceral malignancy, is diagnosed in male individuals. Herein, in order to obtain immune-based subtypes, we performed an integrative analysis to characterize molecular subtypes based on immune-related genes, and further discuss the potential features and differences between identified subtypes. Simultaneously, we also construct an immune-based risk model to assess cancer prognosis. Our findings showed that the two subtypes, C1 and C2, could be characterized, and the two subtypes showed different characteristics that could clearly describe the heterogeneity of immune microenvironments. The C2 subtype presented a better survival rate than that in the C1 subtype. Further, we constructed an immune-based prognostic model based on four screened abnormally expressed genes, and they were selected as predictors of the robust prognostic model (AUC = 0.968). Our studies provide reference for characterization of molecular subtypes and immunotherapeutic agents against prostate cancer, and the developed robust and useful immune-based prognostic model can contribute to cancer prognosis and provide reference for the individualized treatment plan and health resource utilization. These findings further promote the development and application of precision medicine in prostate cancer.

A comprehensive multi-omics analysis reveals molecular features associated with cancer via RNA cross-talks in the Notch signaling pathway.

The Notch signaling has an important role in multiple cellular processes and is related to carcinogenic process. To understand the potential molecular features of the crucial Notch pathway, a comprehensive multi-omics analysis is performed to explore its contributions in cancer, mainly including analysis of somatic mutation landscape, pan-cancer expression, ncRNA regulation and potential prognostic power. The screened 22 Notch core genes are relative stable in DNA variation. Dynamic expression patterns are associated with the Notch activity, which are mainly regulated by multiple ncRNAs via interactions of ncRNA:mRNA and ceRNA networks. The Notch pathway shows a potential prognostic ability through integrating multi-omics features as well as their targets, and it is correlated with immune infiltration and maybe available drug targets, implying the potential role in individualized treatment. Collectively, all of these findings contribute to exploring crucial role of the key pathway in cancer pathophysiology and gaining mechanistic insights into cross-talks among RNAs and biological pathways, which indicates the possible application of the well-conserved Notch signaling pathway in precision medicine.

Embedded polyzwitterionic brush-modified nanofibrous membrane through subsurface-initiated polymerization for highly efficient and durable oil/water separation.

HYPOTHESIS: Developing separation membranes functionalized by polymer brushes with high separation efficiency and good cycling stability is of great importance for oil/water separation, yet is still challenged. EXPERIMENTS: In this work, the covalently embedded polyzwitterionic brush-functionalized nanofibrous membrane was developed for efficient and durable oil/water separation. The nanofibrous membrane was prepared by the electrospinning method using initiator-embedded polyacrylonitrile (PAN) resin, followed by novel subsurface-initiated atom transfer radical polymerization (SSI-ATRP) to graft embedded poly(sulfobetaine methacrylate) brushes (PSBMA). The hydration ability, underwater oil adhesion, oil/water separation performance as well as self-cleaning properties of the as prepared membrane (PAN-sg-PSBMA) were systematically studied. FINDINGS: The PAN-sg-PSBMA membrane exhibited extraordinary hydration ability and underwater superoleophobicity with extremely low oil adhesion, which outperformed conventional polymer brush-modified membrane (PAN-g-PSBMA). The PAN-sg-PSBMA membrane was able to separate both oil/water mixture and surfactant-stabilized emulsions with ultrahigh permeation flux and separation efficiency. Moreover, compared with PAN-g-PSBMA, PAN-sg-PSBMA membrane exhibited unprecedented recycling stability in both permeation flux and separation efficiency, which is attributed to mechanical robustness of embedded polymer brushes and outstanding antifouling ability. The current findings revealed that embedded polymer brushes from SSI-ATRP could offer a promising design of functionalized nanofibrous membrane for highly efficient and durable oil/water separation.

Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy.

Myeloid-derived suppressor cells(MDSCs)are one of the most important immunosuppressive cells in tumor microenvironment, which also promote the development and progression of tumor cells. Nevertheless, due to the different distribution features of MDSCs and tumor cells, selective elimination of MDSCs and tumor cells in tumor microenvironment remain a great challenge. Here we have designed a dual-pH-sensitivity conjugated micelle system (PAH/RGX-104@PDM/PTX) that could deliver liver-X nuclear receptor (LXR) agonist RGX-104 and paclitaxel (PTX) to the perivascular region and tumor cells, respectively. Upon arrival at the acidic tumor microenvironment, the PAH/RGX-104@PDM/PTX undergo structure disintegration and capacitate coinstantaneous release of RGX-104 in the perivascular regions, leaving the intact PTX containing micelles PDM/PTX for tumor deep penetration. The released RGX-104 can be preferentially taken up by leukocytes, endothelial cells and macrophages which are nicely enriched in perivascular regions to active the LXR, and further reduces immunosuppressive MDSC levels. The remained small micelles carrying PTX enable deep tumor penetration as well as rapid specific drug release in the endosomal/lysosomal to kill tumor cells. PAH/RGX-104@PDM/PTX exhibits superior tumor accumulation as well as tumor penetration, and suppresses 74.88% in vivo tumor growth. More importantly, PAH/RGX-104@PDM/PTX has significantly alleviated tumor immunosuppression by eliminating MDSCs and increasing cytotoxic T lymphocytes infiltration. Our studies suggest that the dual-pH-sensitive codelivery nanocarrier not only cause apoptosis of cancer cells but also regulate the tumor immune environment to ultimately enhance the antitumor effect of CTLs through MDSCs depletion.

Houshiheisan promotes angiogenesis via HIF-1α/VEGF and SDF-1/CXCR4 pathways: in vivo and in vitro.

RATIONALE: Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has remarkable efficacy in the treatment of ischemic stroke. OBJECTIVE: To investigate the pro-angiogenic effect and molecular mechanism of HSHS for stroke recovery. METHODS AND RESULTS: The rat permanent middle cerebral artery occlusion (pMCAO) model was constructed by suture method, HSHS (5.25 or 10.5 g/kg) and Ginaton (28 mg/kg) treatment was intragastrically administrated at 6 h after modeling which remained for 7 consecutive days. Pathological evaluation conducted by Hematoxylin-Eosin (HE) staining and the results showed that HSHS alleviated blood vessel edema, reduced the damage to blood vessels and neurons in the ischemic areas. Immunostaining, quantitative real-time fluorescence PCR results showed that HSHS up-regulated pro-angiogenic factors including platelet endothelial cell adhesion molecule-1 (cluster of differentiation 31 (CD31)), vascular endothelial growth factor (VEGF), vascular endothelial growth factor A (VEGFA), VEGF receptor 2 (VEGFR2), angiopoietin-1 (Ang-1), while down-regulated angiopoietin-2 (Ang-2), stromal cell derived factor-1 (SDF-1), and cxc chemokine receptor 4 (CXCR4) expression in infarct rat cortex, and similar results were obtained in subsequent Western blot experiment. Furthermore, CCK8 assay and transwell migration assay were performed to assess cell proliferation, migration, and tube formation. The medicated serum (MS) of HSHS appeared to have beneficial effects for immortalized human umbilical vein cells (Im-HUVECs) on proliferation and migration after persistence hypoxia. Western blot analysis revealed that the expression of hypoxia inducible factor-1α (HIF-1α), VEGFA, Ang-1, Ang-2, and CXCR4 were significantly up-regulated while Ang-2 was down-regulated by HSHS MS treatment compared with vehicle group in vitro. CONCLUSION: The present study suggests a novel application of HSHS as an effective angiogenic formula for stroke recovery.

Reversely Orthogonal Actuation of a Janus-Faced Film Based on Asymmetric Polymer Brush Modification.

The actuation phenomena of materials upon external stimulus have attracted much attention for the development of excellent sensors and devices. Herein, we present a smart Janus-faced film that exhibits novel behavior of reverse orthogonal actuation under high humidity and a positive actuation under low humidity, which is achieved by asymmetric polymer brushes on polydimethysiloxane as a substrate through surface-initiated atom transfer radical polymerization. The classical theory of plates and shells and finite element simulations are also applied to understand the orthogonal actuation mechanism of the actuator. This Janus-faced film can reversely grab objects rapidly under high humidity, which provides significant potential to design a more intelligent actuator. In addition, this film is highly sensitive to humidity that even the approaching finger can make it to bend, which is just like the actuation behavior of Mimosa pudica. Based on the above phenomena, we also design the sensing devices to realize the detection of humidity. Interestingly, the film intelligently identifies different solvents (e.g., water and ethanol). This work may demonstrate significant potential in smart surface modifications, flexible robots, bionic sensors, and other fields.