Water Impalement Resistance and Drag Reduction of the Superhydrophobic Surface with Hydrophilic Strips.

Superhydrophobic surfaces (SHS) offer versatile applications by trapping an air layer within microstructures, while water jet impact can destabilize this air layer and deactivate the functions of the SHS. The current work presents for the first time that introducing parallel hydrophilic strips to SHS (SHS-s) can simultaneously improve both water impalement resistance and drag reduction (DR). Compared with SHS, SHS-s demonstrates a 125% increase in the enduring time against the impact of water jet with velocity of 11.9 m/s and a 97% improvement in DR at a Reynolds number of 1.4 × 104. The key mechanism lies in the enhanced stability of the air layer due to air confinement by the adjacent three-phase contact lines. These lines not only impede air drainage through the surface microstructures during water jet impact, entrapping the air layer to resist water impalement, but also prevent air floating up due to buoyancy in Taylor-Couette flow, ensuring an even spread of the air layer all over the rotor, boosting DR. Moreover, failure modes of SHS under water jet impact are revealed to be related to air layer decay and surface structure destruction. This mass-producible structured surface holds the potential for widespread use in DR for hulls, autonomous underwater vehicles, and submarines.

Anti-tumor effect and mechanism of the total biflavonoid extract from S doederleinii on human cervical cancer cells in vitro and in vivo.

In this study, the therapeutic effect and possible mechanism of the total biflavonoid extract of Selaginella doederleinii Hieron (SDTBE) against cervical cancer were originally investigated in vitro and in vivo. First, the inhibition of SDTBE on proliferation of cervical cancer HeLa cells was evaluated, followed by morphological observation with AO/EB staining, Annexin V/PI assay, and autophagic flux monitoring to evaluate the possible effect of SDTBE on cell apoptosis and autophagy. Cell cycle, as well as mitochondrial membrane potential (ΔÑ°m), was detected with flow cytometry. Further, the apoptosis related protein expression and the autophagy related gene LC3 mRNA transcription level were analyzed by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. Finally, the anti-cervical cancer effect of the SDTBE was also validated in vivo in HeLa cells grafts mice. As results, SDTBE inhibited HeLa cells proliferation with the IC50 values of 49.05 ± 6.76 and 44.14 ± 4.75 µg/mL for 48 and 72 h treatment, respectively. The extract caused mitochondrial ΔÑ° loss, induced cell apoptosis by upregulating Bax, downregulating Bcl-2, activating Caspase-9 and Caspase-3, promoting cell autophagy and blocking the cell cycle in G0/G1 phase. Furthermore, 100, 200, and 300 mg/kg SDTBE suppressed the growth of HeLa cells xenografts in mice with the mean inhibition rates, 25.3 %, 57.5 % and 62.9 %, respectively, and the change of apoptosis related proteins and microvascular density was confirmed in xenografts by immunohistochemistry analysis. The results show that SDTBE possesses anti-cervical cancer effect, and the mechanism involves in activating Caspase-dependent mitochondrial apoptosis pathway.

Geometric constraint-triggered collagen expression mediates bacterial-host adhesion.

Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.

Quaternized carbon dots with enhanced antimicrobial ability towards Gram-negative bacteria for the treatment of acute peritonitis caused by E. coli.

Infections caused by Gram-negative bacteria still pose a clinical challenge. Although nanomaterials have been developed for antibacterial treatments, a systematic evaluation of the mechanisms and intervention models of antibacterial materials toward Gram-negative bacteria is still lacking. Herein, antibacterial quaternized carbon dots (QCDs) were synthesized via a one-step melting method using anhydrous citric acid and diallyl dimethyl ammonium chloride (DDA). The QCDs exhibited effective broad-spectrum antibacterial activity and enhanced inhibitory ability towards Gram-negative bacteria. The antibacterial mechanism of the QCDs with respect to Gram-negative bacteria was investigated through the characterization of bacterial morphology changes, the absorption modes of the QCDs on bacteria, and the potential generation of reactive oxygen species by the QCDs. The QCDs showed low toxicity in different cells, and did not cause hemolysis. The QCDs were administered via intraperitoneal injection to treat acute peritonitis in mice infected with E. coli. Routine blood examination, magnetic resonance imaging, and pathological analysis were undertaken and it was found that, similar to the positive control group treated with gentamicin sulfate, the QCDs exhibited a therapeutic effect that eliminated infection and inflammation. This study explores a controllable synthetic strategy for the synthesis of active carbon dots with antibacterial activity, a material that is a promising candidate for new treatments of Gram-negative bacterial infections.

High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

Cell invasion/migration through three-dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D-CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real-time, label-free, nondestructive, and high-throughput way. In combination with 3D topological networks and complex impedance detection technology, this work shows that 3D-CIMA can quantitively characterize collective invasion/migration dynamics of cancer cells in 3D extracellular matrix (ECM) with controllable biophysical/biomechanical properties. More importantly, this work further reveals that it has the capability to not only carry out quantitative evaluation of anti-tumor drugs in 3D microenvironments that minimize the impact of cell culture dimensions, but also grade clinical cancer specimens. The proposed 3D-CIMA offers a new quantitative methodology for investigating cell interactions with 3D extracellular microenvironments, which has potential applications in various fields like mechanobiology, drug screening, and even precision medicine.

A High-Temperature Superconducting Bandpass Dual-Mode Filter with Tunable Relative Bandwidth and Center Frequency.

This study proposes a high-temperature superconducting (HTS) bandpass filter with a continuously tunable bandwidth and center frequency. The proposed filter combines several gallium arsenide varactors and a dual-mode resonator (DMR). The even and odd modes of the DMR can be tuned simultaneously using a single bias voltage. The capacitive value of varactors in the circuit is tuned continuously under continuous voltage and frequency tunability. External couplings and the interstage can be realized using an interdigital coupling structure; a fixed capacitor is added to the feeder to improve its coupling strength. A low-insertion loss within the band is obtained using HTS technology. Additionally, the proposed filter is etched on a 0.5 mm-thick MgO substrate and combined with YBCO thin films for demonstration. For the as-fabricated device, the tuning frequency range of 1.22~1.34 GHz was 9.4%; the 3-dB fractional bandwidth was 12.95~17.39%, and the insertion loss was 2.28~3.59 dB. The simulation and experimental measurement results were highly consistent.

Extracellular Matrix Rigidities Regulate the Tricarboxylic Acid Cycle and Antibiotic Resistance of Three-Dimensionally Confined Bacterial Microcolonies.

As a major cause of clinical chronic infection, microbial biofilms/microcolonies in host tissues essentially live in 3D-constrained microenvironments, which potentially modulate their spatial self-organization and morphodynamics. However, it still remains unclear whether and how mechanical cues of 3D confined microenvironments, for example, extracellular matrix (ECM) stiffness, exert an impact on antibiotic resistance of bacterial biofilms/microcolonies. With a high-throughput antibiotic sensitivity testing (AST) platform, it is revealed that 3D ECM rigidities greatly modulate their resistance to diverse antibiotics. The microcolonies in 3D ECM with human tissue-specific rigidities varying from 0.5 to 20 kPa show a ≈2-10 000-fold increase in minimum inhibitory concentration, depending on the types of antibiotics. The authors subsequently identified that the increase in 3D ECM rigidities leads to the downregulation of the tricarboxylic acid (TCA) cycle, which is responsible for enhanced antibiotic resistance. Further, it is shown that fumarate, as a potentiator of TCA cycle activity, can alleviate the elevated antibiotic resistance and thus remarkably improve the efficacy of antibiotics against bacterial microcolonies in 3D confined ECM, as confirmed in the chronic infection mice model. These findings suggest fumarate can be employed as an antibiotic adjuvant to effectively treat infections induced by bacterial biofilms/microcolonies in a 3D-confined environment.

Purse-string contraction guides mechanical gradient-dictated heterogeneous migration of epithelial monolayer.

Mechanical heterogeneity has been recognized as an important role in mediating collective cell migration, yet the related mechanism has not been elucidated. Herein, we fabricate heterogeneous stiffness gradients by leveraging microelastically-patterned hydrogels with varying periodic distance. We observe that a decrease in the periodic distance of the mechanical heterogeneity is accompanied by an overall increase in the velocity and directionality of the migrating monolayer. Moreover, inhibition of ROCK- and myosin ⅡA- but not Rac1-mediated contraction reduces monolayer migration on the mechanically heterogeneous substrates. Furthermore, we find that F-actin and myosin ⅡA form purse-string at the leading edge on the mechanically heterogeneous substrates. Together, these findings not only show that the orientational cell-cell contraction promotes collective cell migration under the mechanical heterogeneity, but also demonstrate that the mechanosensation arising from large-scale cell-cell interactions through purse-string formation mediated cell-cell orientational contraction can feed back to regulate the reorganization of epithelial tissues. STATEMENT OF SIGNIFICANCE: By detecting the links between heterogenous rigidity and collective cell migration behavior at the molecular level, we reveal that collective cell migration in the mechanical heterogeneity is driven by ROCK- and myosin-ⅡA-dependent cytoskeletal tension. We confirm that cytoskeletal tension across the epithelial tissue is holistically linked through F-actin and myosin-ⅡA, which cooperate to form purse-string structures for modulating collective tissue behavior on the exogenous matrix with mechanical heterogeneity. Mechanical heterogeneity initiates tissue growth, remodelling, and morphogenesis by orientating cell contractility. Therefore, tensional homeostasis across large-scale cell interactions appears to be necessary and sufficient to trigger collective tissue behavior. Overall, these findings shed light on the role of mechanical heterogeneity in tissue microenvironment for reorganization and morphogenesis.

Catch bond-inspired hydrogels with repeatable and loading rate-sensitive specific adhesion.

Biological receptor-ligand adhesion governed by mammalian cells involves a series of mechanochemical processes that can realize reversible, loading rate-dependent specific interfacial bonding, and even exhibit a counterintuitive behavior called catch bonds that tend to have much longer lifetimes when larger pulling forces are applied. Inspired by these catch bonds, we designed a hydrogen bonding-meditated hydrogel made from acrylic acid-N-acryloyl glycinamide (AA-NAGA) copolymers and tannic acids (TA), which formed repeatable specific adhesion to polar surfaces in an ultra-fast and robust way, but hardly adhered to nonpolar materials. It demonstrated up to five-fold increase in shear adhesive strength and interfacial adhesive toughness with external loading rates varying from 5 to 500 mm min-1. With a mechanochemical coupling model based on Monte Carlo simulations, we quantitatively revealed the nonlinear dependence of rate-sensitive interfacial adhesion on external loading, which was in good agreement with the experimental data. Likewise, the developed hydrogels were biocompatible, possessed antioxidant and antibacterial properties and promoted wound healing. This work not only reports a stimuli-responsive hydrogel adhesive suitable for multiple biomedical applications, but also offers an innovative strategy for bionic designs of smart hydrogels with loading rate-sensitive specific adhesion for various emerging areas including flexible electronics and soft robotics.

Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal.

Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9+ progenitors by activating the Wnt/ß-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.

Controlled magnesium ion delivery system for in situ bone tissue engineering.

Magnesium cation (Mg2+) has been an emerging therapeutic agent for inducing vascularized bone regeneration. However, the therapeutic effects of current magnesium (Mg) -containing biomaterials are controversial due to the concentration- and stage-dependent behavior of Mg2+. Here, we first provide an overview of biochemical mechanism of Mg2+ in various concentrations and suggest that 2-10 mM Mg2+in vitro may be optimized. This review systematically summarizes and discusses several types of controlled Mg2+ delivery systems based on polymer-Mg composite scaffolds and Mg-containing hydrogels, as well as their design philosophy and several parameters that regulate Mg2+ release. Given that the continuous supply of Mg2+ may prevent biomineral deposition in the later stage of bone regeneration and maturation, we highlight the controlled delivery of Mg2+ based dual- or multi-ions system, especially for the hierarchical therapeutic ion release system, which shows enhanced biomineralization. Finally, the remaining challenges and perspectives of Mg-containing biomaterials for future in situ bone tissue engineering are discussed as well.

DNA hydrogels as selective biomaterials for specifically capturing DNA, protein and bacteria.

The ability to selectively capture biomacromolecules and other components from solution has many important applications in biotechnology. However, capturing targets from solution while minimizing interference with the sample solution is still challenging. Here, we describe the design and assembly of a group of DNA hydrogels consisting of long single-stranded DNA produced by rolling amplification reaction (RCA) and crosslinked by DNA duplexes. The developed DNA hydrogels can selectively capture and separate oligonucleotides, proteins and bacteria from solution in situ without complex separation processes. Since such DNA hydrogels can capture their targets in the solution independently, multiple DNA hydrogels that target different compounds can be employed to separate different compounds in the solution at the same time. The work not only expands the application of DNA hydrogels, but also paves the way for developing novel selective biomaterials. STATEMENT OF SIGNIFICANCE: Biomaterials capable of selectively capturing various components have great potential in the field of biotechnology. Here, we proposed a new class of hydrogel composed of crosslinked long DNA strands for selectively capturing DNA, protein and bacteria. Unlike traditional polymeric hydrogels that have small meshes and limit macromolecule diffusion owing to the short distance between two adjacent crosslinks, the described DNA hydrogel has a much larger distance between its crosslinks because of the sequence designability of DNA, which allows easy diffusion of biomacromolecules through its networks and greatly expand its specific surface area. Moreover, the developed DNA hydrogel can also easily combine different aptamers to target different components via the Watson-Crick base pairing without making significant changes in its original design.

Construction of multifunctional cell aggregates in angiogenesis and osteogenesis through incorporating hVE-cad-Fc-modified PLGA/ß-TCP microparticles for enhancing bone regeneration.

Multicellular aggregates have been widely utilized for regenerative medicine; however, the heterogeneous structure and undesired bioactivity of cell-only aggregates hinder their clinical translation. In this study, we fabricated an innovative kind of microparticle-integrated cellular aggregate with multifunctional activities in angiogenesis and osteogenesis, by combining stem cells from human exfoliated deciduous teeth (SHEDs) and bioactive composite microparticles. The poly(lactide-co-glycolide) (PLGA)-based bioactive microparticles (PTV microparticles) were ∼15 µm in diameter, with dispersed ß-tricalcium phosphate (ß-TCP) nanoparticles and surface-modified vascular endothelialcadherin fusion protein (hVE-cad-Fc). After co-culturing with microparticles in U-bottomed culture plates, SHEDs could firmly attach to the microparticles with a homogeneous distribution. The PTV microparticle-integrated SHED aggregates (PTV/SHED aggregates) showed significant positive CD31 and ALP expression, as well as the significantly upregulated osteogenesis makers (Runx2, ALP, and OCN) and angiogenesis makers (Ang-1 and CD31), compared with PLGA, PLGA/ß-TCP (PT) and PLGA/hVE-cad-Fc (PV) microparticle-integrated SHED aggregates. Finally, in mice, 3 mm calvarial defects filled with the PTV microparticle-integrated SHED aggregates achieved abundant vascularized neo-bone regeneration within 4 weeks. Overall, we believe that these multifunctional PTV/SHED aggregates could be used as modules for bottom-up regenerative medicine, and provide a promising method for vascularized bone regeneration.

Mechanical transmission enables EMT cancer cells to drive epithelial cancer cell migration to guide tumor spheroid disaggregation.

Cell phenotype heterogeneity within tumor tissue, especially which due to the emergence of epithelial-mesenchymal transition (EMT) in cancer cells, is associated with cancer invasion and metastasis. However, our understanding of the cellular mechanism(s) underlying the cooperation between EMT cell and epithelial cancer cell migration remains incomplete. Herein, heterotypic tumor spheroids containing both epithelial and EMT cancer cells were generated in vitro. We observed that EMT cells dominated the peripheral region of the self-organized heterotypic tumor spheroid. Furthermore, our results demonstrated that EMT cells could serve as leader cells to improve the collective migration efficiency of epithelial cancer cells and promote dispersion and invasion of the tumor spheroids, which was regulated by the force transition between EMT cells and epithelial cancer cells. Mechanistically, our data further suggest that force transmission is mediated by heterophilic N-cadherin/E-cadherin adhesion complexes between EMT and epithelial cancer cells. Impairment of N-cadherin/E-cadherin adhesion complex formation abrogated the ability of EMT cells to guide epithelial cancer cell migration and blocked the dispersion of tumor spheroids. Together, our data provide new insight into the mechanical interaction between epithelial and EMT cancer cells through heterophilic cadherin adhesion, which enables cooperative tumor cell migration, highlighting the role of EMT cells in tumor invasion.

Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration.

Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy.

Deep-learning-based 3D cellular force reconstruction directly from volumetric images.

The forces exerted by single cells in the three-dimensional (3D) environments play a crucial role in modulating cellular functions and behaviors closely related to physiological and pathological processes. Cellular force microscopy (CFM) provides a feasible solution for quantifying mechanical interactions, which usually regains cellular forces from deformation information of extracellular matrices embedded with fluorescent beads. Owing to computational complexity, traditional 3D-CFM is usually extremely time consuming, which makes it challenging for efficient force recovery and large-scale sample analysis. With the aid of deep neural networks, this study puts forward a novel, data-driven 3D-CFM to reconstruct 3D cellular force fields directly from volumetric images with random fluorescence patterns. The deep-learning-based network is established through stacking deep convolutional neural networks (DCNN) and specific function layers. Some necessary physical information associated with constitutive relation of extracellular matrix material is coupled to the data-driven network. The mini-batch stochastic-gradient-descent and back-propagation algorithms are introduced to ensure its convergence and training efficiency. The networks not only have good generalization ability and robustness but also can recover 3D cellular forces directly from the input fluorescence image pairs. Particularly, the computational efficiency of the deep-learning-based network is at least one to two orders of magnitude higher than that of traditional 3D-CFM. This study provides a novel scheme for developing high-performance 3D-CFM to quantitatively characterize mechanical interactions between single cells and surrounding extracellular matrices, which is of vital importance for quantitative investigations in biomechanics and mechanobiology.

Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth.

Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide-co-glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O1/W/O2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.

Electrically Programmable Interfacial Adhesion for Ultrastrong Hydrogel Bonding.

Adjustable interfacial adhesion is of great significance in smart-hydrogel-related engineering fields. This study presents an electroadhesion strategy for universal and ultrastrong hydrogel bonding with electrically programmable strength. An ionic hydrogel containing lithium ions is designed to achieve hydrated-ion-diffusion-mediated interfacial adhesion, where external electric fields are employed to precisely control spatiotemporal dynamics of the ion diffusion across ionic adhesion region (IAR). The hydrogel can realize a universal, ultrastrong, efficient, tough, reversible, and environmentally tolerant electroadhesion to diverse hydrogels, whose peak adhesion strength and interfacial adhesion toughness are as high as 1.2 MPa and 3750 J m-2 , respectively. With a mechanoelectric coupling model, the dominant role of the hydrated ions in IAR played in the interfacial electroadhesion is further quantitatively revealed. The proposed strategy opens a door for developing high-performance adhesion hydrogels with electrically programmable functions, which are indispensable for various emerging fields like flexible electronics and soft robotics.

Recent progress (2015-2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb1, a main active ingredient in Panax ginseng Meyer.

Ginsenoside Rb1 (Rb1), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb1 against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb1 on these diseases are referring to HMGB1, GLUT4, 11ß-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-ß1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb1 and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb1 and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb1 and its clinical applications.