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The high disability, mortality and morbidity of diabetic ulcers make it urgent to explore effective strategies for diabetic wound repair. TrxR1 plays a vital role in regulating redox homeostasis in various pathologies. In the present study, the effect of berberine (BBR) on diabetic wounds was investigated in streptozotocin (STZ)-induced diabetic rats and a high glucose (HG)-induced cell model, and the mechanism of BBR on TrxR1 was elucidated. BBR treatment remarkably accelerated wound healing and enhanced extracellular matrix (ECM) synthesis and significantly inhibited HG-induced HaCaT cell damage. Further analysis indicated that BBR activated TrxR1, suppressed its downstream JNK signaling, thereby inhibiting oxidative stress and apoptosis, promoted cell proliferation, down-regulated matrix metalloproteinase (MMP) 9 (MMP9) and up-regulated transforming growth factor-β1 (TGF-β1) and tissue inhibitors of MMP 1 (TIMP1), resulting in accelerated wound healing. Importantly, the enhancement of BBR on wound repair was further abolished by TrxR1 inhibitor. Moreover, in diabetic wounds induced by a combination of STZ injection and high-fat diet, BBR significantly increased wound closure rate and TrxR1 expression, and this was reversed by TrxR1 inhibitor. These data indicated that topical BBR treatment accelerated diabetic wound healing by activating TrxR1. Targeting TrxR1 may be a novel, effective strategy for restoring redox homeostasis and promoting diabetic wound healing.

Myocardial infarction (MI) is one of the leading causes of death worldwide. However, there is no effective treatment for MI. In this study, trimetazidine (TMZ) and Danhong injection (DHI), representing western medicine and traditional Chinese medicine for MI, were used as tools to identify vital processes in alleviating MI injury. Administration of DHI and TMZ obviously decreased myocardial infarct size, improved ultrasonic heart function, and reduced creatine kinase (CK), lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (AST) levels after MI. RNA-seq results indicated calcium ion handling and negative regulation of apoptotic process were vital processes and DHI and TMZ obviously reduced the expression of CaMK II and inhibited cleaved caspase-3 and Bax. Furthermore, DHI and TMZ increased p-S16-PLB, p-S16T17-PLB, CACNA1C, p-RyR2, and p-PKA expression but did not affect SERCA2a expression. In addition to the enhancement of cardiac myocyte shortening amplitude, maximum shortening velocity, and calcium transients, DHI and TMZ increased sarcoplasmic reticulum calcium content and enhanced SERCA2a calcium uptake capability by upregulating the phosphorylation of PLB but did not affect calcium exclusion by NCX. In conclusion, DHI and TMZ protect against MI through inhibiting apoptosis by downregulating CaMKII pathway and enhancing cardiac myocyte contractile functions possibly through the PKA signaling pathway.

As a relatively new physiological signal of brain, functional near-infrared spectroscopy (fNIRS) is being used more and more in brain–computer interface field, especially in the task of motor imagery. However, the classification accuracy based on this signal is relatively low. To improve the accuracy of classification, this paper proposes a new experimental paradigm and only uses fNIRS signals to complete the classification task of six subjects. Notably, the experiment is carried out in a non-laboratory environment, and movements of motion imagination are properly designed. And when the subjects are imagining the motions, they are also subvocalizing the movements to prevent distraction. Therefore, according to the motor area theory of the cerebral cortex, the positions of the fNIRS probes have been slightly adjusted compared with other methods. Next, the signals are classified by nine classification methods, and the different features and classification methods are compared. The results show that under this new experimental paradigm, the classification accuracy of 89.12% and 88.47% can be achieved using the support vector machine method and the random forest method, respectively, which shows that the paradigm is effective. Finally, by selecting five channels with the largest variance after empirical mode decomposition of the original signal, similar classification results can be achieved.

In this article, boundary control strategy is adopted to suppress the vibration of a flexible three-dimensional (3D) marine riser simultaneously against both sensor and actuator faults. The flexible 3D marine riser is a distributed parameter system modeled as partial differential equations. During normal operation of the system, all the system components will behave optimally. However, if the sensor and actuator appear fault, the system will work abnormally. While the sensor is faulty, the output signal of the sensor will have errors, and this error signal will be the input signal of the actuator. In terms of actuator fault, once the actuator appears fault problem, the actuator should make up for the fault and continue working for the sake of safety. In this work, the fault degree of sensors and actuators are unknown and the boundary control schemes using Nassbaum function are developed for fault compensation. The system stability is proven by introducing an appropriate Lyapunov function. Finally, the simulation results verify the accuracy of the proposed control laws.

An acid-resistant nanofiltration (NF) membrane with high permeability and rejection is of great significance. A NF membrane was prepared via interfacial polymerization with the assistance of surfactants, where three different common surfactants were used: sodium dodecyl sulfate (SDS), sodium lauryl sulfonate, and sodium dodecyl benzenesulfonate. The addition methods of SDS were optimized, with the results showing that using SDS to activate the substrate surface significantly affects the membrane performance. The surfactant was firstly deposited on a poly(ether)sulfone (PES) support layer prior to the interfacial polymerization of polyethyleneimine (PEI) and cyanuric chloride (CC) to form an active layer. The presence of SDS on the surface of the PES support membrane improves the retention of PEI in the process of the membrane preparation, thus affecting the morphology and cross-linking degree of the membrane, and ultimately affecting its performance. The NF membrane prepared under optimized conditions exhibits a water flux of 144.7 L m−2 h−1, while its rejection of MgCl2 was 92.2%, with a decline in the rejection after one-month of acid soaking tests to give a value that is lower by 1.7%. The prepared NF membrane has good water flux and rejection properties, and exhibits long-term acid resistance.

Solar-driven interfacial evaporation is one of the most promising technologies to obtain freshwater using solar energy. Many promising approaches have been proposed for solar steam generation. However, some problems (the lack of scalability, flexibility, convenience, stability, washability, etc.) in most of these approaches severely restrict their future industrial applications. Herein, utilizing a convenient textile weaving technique, we demonstrate a carbon fiber and cotton yarn mixture fabric, which can achieve high-performance solar steam generation because of the stable and high light-absorption of the carbon fiber and the special structure of the fabric. The manipulation of woven fabric structures can regulate the light absorption and water content in this fabric. The optimized fabric can achieve high photothermal efficiency (1.87 kg m−2 h−1) under 1 sun illumination. In particular, an all-in-one and large-scale device with anti-salt clogging is easily obtained by adjusting the number of warp threads and the width of weft threads. This designed fabric demonstrates significant potential in achieving affordable clean water from seawater and other wastewater, thus providing a new pathway for the development of high-efficiency, scalable, and stable solar interfacial evaporators.

A reliable method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to conduct a comprehensive analysis of the chemical constituents of Du-zhi pill (DZP) as well as their metabolites in rat plasma, urine and feces after gastric perfusion. The efficient on-line mass data acquisition modes combined the various off-line mass data mining strategy was applied. A full mass scan was performed, and then accurate MS/MS datasets were obtained through the use of a multiple mass defect filter (MMDF) and dynamic background subtraction (DBS)-dependent data acquisition method. Furthermore, post-acquisition data processing was conducted using various data-mining tools, including extracted ion chromatography (XIC), mass defect filtering (MDF), product ion filtering (PIF), and neutral loss filtering (NLF) (MetabolitePilot™). Finaly, a total of 176 compounds were identified or tentatively characterized in DZP. Moreover, a total of 233 components in vivo, which includes 92 prototype components and 141 metabolites, were unambiguously or tentatively identified in rat plasma, urine and feces. The metabolic pathways, including phase I reactions (hydroxylation, dehydroxylation and hydrogenation) and phase II reactions (acetylation, sulfation, glucuronidation and methylation), for the absorbed constituents, were explored and summarized. This is the first systematic study on the components of DZP and their metabolites in vivo. This study provide a valid analytical strategy for the characterization of chemical compounds and metabolites of TCM formulas. Moreover, an integrative strategy was proposed for the characterization and identification of chemical constituents and metabolites for additional TCM prescriptions.

PurposeThe increasing social media use has been widely recognized for its adverse effects, such as social media fatigue. With the continuously increasing friends on social media, the dissimilarity of individuals in terms of age, personality, and values has increased. It is unclear whether perceived dissimilarity with others is associated with social media fatigue. The authors attempted to bridge this gap by constructing a “perception–emotion–behavioral” research framework. This study investigated the influence of individual perceived dissimilarity on social media fatigue. The authors further investigated the mechanisms mediating the three dimensions of social anxiety in the model.Design/methodology/approachThis study examined the mechanisms by which individual perceived dissimilarity influences social media fatigue, particularly using WeChat application. A field survey study conducted in China with 408 subjects of WeChat app users was used in this study to analyze the study model.FindingsThe obtained results demonstrate that individual perceived dissimilarity has a significant positive effect contributing to social media fatigue, perceived dissimilarity is positively correlated to social anxiety. Social anxiety positively affects social media fatigue, and social anxiety partially mediates the positive effect between perceived dissimilarity and social media fatigue.Originality/valueFirst, the study confirmed the influence of perceived dissimilarity on social media fatigue, which may enrich the antecedent mechanisms of social media fatigue. Second, the authors demonstrated the social anxiety-mediated development of fatigue. The findings provide an in-depth understanding of users' fatigue. Third, the findings of this study provide valuable insights for preventing of social media fatigue.

Identification of the drug target of lead compounds is an important means for rapid and efficient drug discovery. Protein chips are a high-throughput protein function analysis technology that has been widely used in screening drug protein targets in recent years. However, the verification of the results after high-throughput protein chip screening is still cumbersome. Based on our mature protein chip preparation platform, we prepared a protein chip containing 150 important high-frequency protein targets and used antibodies to prove the availability of the protein chip. To improve the accuracy of target screening, we combined the label-free differential scanning fluorimetry (DSF) with the protein chip, proposing the Chip-DSF strategy. Subsequently, we tested the method with small molecular ginsenoside-Rg2 (Rg2). The Chip-DSF strategy was used to successfully screen the potential target protein KRAS(G12C) of Rg2. Consistently, we found that Rg2 could inhibit NCI-H23 cell proliferation by inducing cell cycle arrest. Also, we found that Rg2 could reduce the amount of KRAS protein and inhibit the phosphorylation of KRAS downstream key signaling protein ERK1, RPS6, and P70S6K in NCI-H23 cells. Collectively, our Chip-DSF strategy could achieve rapid target verification which improved the accuracy and efficiency of target screening of protein chips.

The phase equilibria of the ternary system (Li2CO3–Na2CO3–H2O) at 278.15 ≤ T/K ≤ 308.15 K were investigated by isothermal dissolution equilibrium. On the basis of the experimental data, the phase d...

For stroke patients, hand function assessment is an important part of the hand rehabilitation process. The hand function assessment, however, requires the patient to complete a series of actions un...

Summary Modeling and vibration control of a bridge beam system are considered in this article. The beam bridge with both ends fixed can be regarded as an Euler‐Bernoulli beam, which is a typical di...

A sliding mode control method is developed in this study for application to a class of underactuated systems with bounded unknown disturbance and sensor and actuator faults. In the proposed method,...

In this study, we evaluate the coordination tracking control problem of a flexible master–slave teleoperation system. The system under consideration is based on a dynamic model described by a set of partial differential equations. Existing research on bilateral controllers is based on teleoperation systems composed of rigid master robots and rigid or flexible slave robots. In this work, we consider teleoperation systems with flexible master and slave robots. We dynamically model flexible master–slave manipulators using partial differential equations. Based on the dynamic model, a bilateral coordination controller is developed to realize the coordination angle tracking and vibration suppression of flexible master–slave manipulators. The teleoperation system is proven to be asymptotically stable under the control scheme. Numerical simulation results illustrate that the proposed controller is effective.

In order to imitate wood truly in structure and content, a viscose solution was used to prepare a cellulose membrane with the hierarchically porous structure of wood by two-step process of ice-templating and low-temperature phase inversion for a solar steam device. The prepared cellulose membrane with microchannels observed by microscopy, which resembled those of wood, showed excellent wicking and water flux characteristics. The physical properties of cellulose membranes, including mechanical and thermal stability, allow their application in many fields. In evaluating of solar steam performance, the water evaporation rate of 1.56 kg m−2 h−1 from a graphene-coated cellulose membrane at the light density of 1 kW m−2 exceeded that of a cellulose membrane with pure water. The water evaporation rate of the cellulose membrane was higher than that of a wood-derived solar steam device. The conversion efficiency was increased from 40.72 to 95.57% with modification of the prepared cellulose membrane using graphene. The collected data showed that the cellulose membrane with a hierarchically porous structure was a promising alternative to wood-based solar steam devices, which have the limitations in the reproducibility of structure and composition.

In this study, we considered the coordination and vibration control for two sets of flexible satellite systems with input constraints and actuator failures. The parameters of both systems were kept uniform, and one was called the master flexible satellite, and the other one was called slave flexible satellite. The two sets of the flexible satellite systems were modelled as partial differential equations. Coordination control laws were designed to turn the master flexible satellite system to the desired angle and then turn the slave system to the angle of the master satellite system. Furthermore, the hyperbolic tangent function was adopted to realize the control input constraint. The adaptive control laws were designed to ensure that the systems work normally even when the actuator fails. Lyapunov’s direct method was adopted and stability analysis was given. Finally, numerical simulations were conducted to validate the results.

An active robust adaptive fault-tolerant control protocol is studied for reducing vibration of crane bridge system and handling actuator faults and output constraints simultaneously based on a partial differential equation model. The closed-loop system subject to environmental perturbations and actuator failures can be stabilized with proposed control laws. Furthermore, output constraints of trolley can always be ensured via employing barrier Lyapunov function (BLF), and uncertain actuator faults can also be compensated availably using developed adaptive control laws without any knowledge of actuator fault information. Finally, numerical simulation is provided for illustrating performance of the proposed control method.

This paper is concerned with the stabilisation problem of an Euler–Bernoulli beam with uncertain parameters and disturbances. To correctly represent the beam's behaviour, the partial differential e...

A three-dimensional solar steam generation device with a high water evaporation rate and excellent structural stability was developed and characterized. The design consisted of a bilayer membrane composed of polyacrylonitrile (PAN) and PAN/graphene oxide (GO) segments and contained vertically aligned porous structures similar to that of wood. This distinctive design was used to improve the water evaporation rate by increasing the light absorption and specific surface area. The prepared bilayer membrane exhibited excellent water wicking and flux, and it could continuously supply water from the bottom of the solar steam generation device to the top surface. The device's performance was evaluated by exposing the PAN/GO surface to artificial sunlight with a density of 1, 5, and 10 kW m

A large number of reactive oxygen species (ROS) aggravate cerebral damage after ischaemia/reperfusion (I/R). Glutathione (GSH), thioredoxin (Trx) and nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) represent three major antioxidant systems and play vital roles in affecting each other in eliminating ROS. Identification of drugs targeting triple antioxidant systems simultaneously is vital for inhibiting oxidative damage after cerebral I/R. This study investigated the protective effect of safflower extract and aceglutamide (SAAG) against cerebral I/R injury through modulating multiple antioxidant systems of GSH, Trx and Nrf2 and identified each role of its component acegluatminde (AG) and safflower extract (SA) on these systems. Safflower extract and aceglutamide and its two components decreased neurological deficit scores, infarction rate, apoptosis and oxidative damage after cerebral I/R while enhanced cell viability, decreased reactive oxygen species and nitric oxide level in H2O2‐induced PC12 cell model. Importantly, compared to its two components, SAAG demonstrated more effective enhancement of GSH, Nrf2 and Trx systems and a better protection against cerebral I/R injury. The enhanced antioxidant systems prevented ASK1 activation and suppressed subsequent p38 and JNK cascade‐mediated apoptosis. Moreover, inhibition of Trx and Nrf2 systems by auranofin and ML385 abolished SAAG‐mediated protection, respectively. Thus, enhanced triple systems by SAAG played a better protective role than those by SA or AG via inhibition of ASK1 cascades. This research provided evidence for the necessity of combination drugs from the perspective of multiple antioxidant systems. Furthermore, it also offers references for the study of combination drugs and inspires novel treatments for ischaemic stroke.

Commercial or clinical tissue adhesives are currently limited due to their weak bonding strength on wet biological tissue surface, low biological compatibility, and slow adhesion formation. Although catechol-modified hyaluronic acid (HA) adhesives are developed, they suffer from limitations: insufficient adhesiveness and overfast degradation, attributed to low substitution of catechol groups. In this study, we demonstrate a simple and efficient strategy to prepare mussel-inspired HA hydrogel adhesives with improved degree of substitution of catechol groups. Because of the significantly increased grafting ratio of catechol groups, dopamine-conjugated dialdehyde-HA (DAHA) hydrogels exhibit excellent tissue adhesion performance (i.e., adhesive strength of 90.0 ± 6.7 kPa), which are significantly higher than those found in dopamine-conjugated HA hydrogels (∼10 kPa), photo-cross-linkable HA hydrogels (∼13 kPa), or commercially available fibrin glues (2-40 kPa). At the same time, their maximum adhesion energy is 384.6 ± 26.0 J m-2, which also is 40-400-fold, 2-40-fold, and ∼8-fold higher than those of the mussel-based adhesive, cyanoacrylate, and fibrin glues, respectively. Moreover, the hydrogels can gel rapidly within 60 s and have a tunable degradation suitable for tissue regeneration. Together with their cytocompatibility and good cell adhesion, they are promising materials as new biological adhesives.

Dynamic properties are vital for the working reliability of aft stern tube bearings. However, the determination of such properties currently involves several simplifications and assumptions. To obtain its dynamic characteristics accurately, the aft stern tube bearing was divided into several bearing segments. The oil film reaction force was considered in the calculation of shaft alignment, and the journal deflection and actual oil film thickness were obtained accordingly. Subsequently, the perturbed Reynolds equation was solved using the finite difference method when the dynamic characteristics of journal bearings with finite width were evaluated. Then, a calculation program was developed and verified by comparing with the results of other studies. Finally, the dynamic characteristics were calculated under different revolutions. The results showed that the stiffness at the vertical direction of the aft stern tube bearing was several times that of the horizontal direction and varied with the revolutions of the shafting system. These findings can provide the foundation for the precise calculation of the journal trajectory under dynamic conditions, as well as for the evaluation of the oil film thickness. Moreover, the results led to favorable conditions for the accurate calculation of the shafting whirling vibration.

This article studies the stability problem for a three-dimensional string with variable length in the case of input quantization. A nonlinear partial differential equation model is used to depict the dynamic characteristics of the length-varying flexible string with distributed variable parameters. The control signals are effectively mapped from a continuous region to a discrete set of numerical signals before being transmitted through communication channels using quantizers. With no information about quantizers, the vibration of the string is eliminated under the proposed adaptive quantized control despite of the actuator degradation, and the stability of the closed-loop system is demonstrated based on the Lyapunov’s direct method. Simulation results are supplied to show the effectiveness of the presented control strategy.

The present work reports acidity (pH), Ranman spectrum, densities (ρ) and viscosity (η) of aqueous lithium metaborate solution at different temperatures. Polyborate distributions in aqueous LiB(OH)4 solution were calculated using measured pH values and literature equilibrium constants. Combining Raman spectra and polyborate distributions result, the polyborate species were ascertained in solution. The apparent molar volumes (Φv), standard molar volumes ($$\Phi _{v}^{0}$$), apparent molar expansibilities ($$\Phi _{E}^{0}$$), and coefficient of thermal expansion (α) in aqueous lithium metaborate solution have been calculated from the density data. The viscosity data have been analyzed by Jones–Dole equation. Different thermodynamic parameters have been used to explore solute–solute, solute–solvent interactions and effect of concentration and temperature. All the parameters calculated from density and viscosity indicate that the lithium metaborate is water structure breaker.

Despite tremendous efforts to improve solar-driven steam generation, most solar evaporators are limited to unidirectional evaporation due to changes in the direction of solar irradiation under real-world conditions. Hence, the development of non-unidirectional evaporators, ideally allowing omnidirectional evaporation, remains a significant challenge. In this work, the first-ever vertically aligned activated carbon–juncus effusus (AC-JE) evaporator (VACJE) for omnidirectional evaporation is demonstrated. AC-JEs are produced by uniformly decorating activated carbon powder (a cost-lost material with broad efficient solar absorption) on the fibril skeletons of JE with interconnected network architectures. The surprising photothermal performance (the evaporation rate of 2.23 kg m−2 h−1 under 1 sun illumination) of the VACJE is attributed to the unique inbuilt interconnected network architecture of JE. This structural feature multiplies the available evaporation area to promote omnidirectional solar evaporation, while also providing excellent light absorption thermal management and salt-resistant. This unexpected finding reveals the hidden potential of JE as a low-cost biomass material and provides inspiration for the future design and development of high-performance solar-driven steam generators.

Global warming has been linked to declines in tree growth. However, it is unclear how the asymmetry in daytime and nighttime warming influences this response. Here, we use 2947 residual tree-ring width chronologies covering 32 species at 2493 sites, between 1901 and 2018, across the Northern Hemisphere, to analyze the effects of daytime and nighttime temperatures, precipitation, and drought stress on the radial growth of trees. We show that drought stress was primarily triggered by daytime rather than nighttime warming. The radial growth of trees was more sensitive to drought stress in warm regions than in cold regions, especially for angiosperms. Our study provides robust evidence that daytime warming is the primary driver of the observed declines in forest productivity related to drought stress and that daytime and nighttime warming should be considered separately when modelling forest-climate interactions and feedbacks in a future, warmer world.

Cardiovascular disease serves as the leading cause of death worldwide, with stenosis, occlusion, or severe dysfunction of blood vessels being its pathophysiological mechanism. Vascular replacement is the preferred surgical option for treating obstructed vascular structures. Due to the limited availability of healthy autologous vessels as well as the incidence of postoperative complications, there is an increasing demand for artificial blood vessels. From synthetic to natural, or a mixture of these components, numerous materials have been used to prepare artificial vascular grafts. Although synthetic grafts are more appropriate for use in medium to large-diameter vessels, they fail when replacing small-diameter vessels. Tissue-engineered vascular grafts are very likely to be an ideal alternative to autologous grafts in small-diameter vessels and are worthy of further investigation. However, a multitude of problems remain that must be resolved before they can be used in biomedical applications. Accordingly, this review attempts to describe these problems and provide a discussion of the generation of artificial blood vessels. In addition, we deliberate on current state-of-the-art technologies for creating artificial blood vessels, including advances in materials, fabrication techniques, various methods of surface modification, as well as preclinical and clinical applications. Furthermore, the evaluation of grafts both in vivo and in vitro, mechanical properties, challenges, and directions for further research are also discussed.

Hyaluronic acid (HA) hydrogel is preferred for biomedicine applications, as it possesses biodegradability, biocompatibility, and cell-regulated capacity as well as high hydration nature similar to the native extracellular matrix. However, HA hydrogel fabricated via a 3D printing technique often faces poor printing properties. In this study, maleiated sodium hyaluronate (MHA) with a high substituted degree of the acrylate group (i.e., 2.27) and thiolated sodium hyaluronate (SHHA) were synthesized. By blending these modified HAs, the MHA/SHHA hydrogels were prepared via pre-crosslinking through thiol-acrylate Michael addition and subsequently covalent crosslinking using thiol-acrylate and acrylate-acrylate photopolymerization mechanisms. Rheological properties, swelling behaviors, and mechanical properties can be modulated by altering the molar ratio of the thiol group and acrylate group. The results showed that the MHA/SHHA hydrogel precursors have rapidly gelling capacity and improved compressive strength. Based on these results, high-resolution hydrogel scaffolds with good structural stability were prepared by extrusion-based 3D printing. This HA hydrogel is cytocompatible and capable of supporting adherence of L929 cells, indicating its great potential for tissue engineering scaffolds.

Diabetic ulcers bring about high morbidity and mortality in patients and cause a great economic burden to society as a whole. Since existing treatments cannot fulfil patient requirements, it is urgent to find effective therapies. In this study, the wound healing effect of topical notoginsenoside R1 (NR1) treatment on diabetic full-thickness wounds in type II diabetes mellitus (T2DM) was induced by the combination of a high-fat diet and streptozotocin (STZ) injection. NR1 significantly increased the wound closure rate, enhanced extracellular matrix (ECM) secretion, promoted collagen growth, increased platelet endothelial cell adhesion molecule-1 (CD31) expression, and decreased cleaved caspase-3 expression. RNA-Seq analysis identified ECM remodeling and inflammation as critical biological processes and Timp1 and Mmp3 as important targets in NR1-mediated wound healing. Further experiments showed that NR1-treated wounds demonstrated higher expression of tissue inhibitor of metalloproteinase 1 (TIMP1) and transforming growth factor-β1 (TGFβ1) and lower expression of matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 3 (MMP3), interleukin-1β (IL-1β), and interleukin-6 (IL-6) than diabetic wounds. These investigations promote the understanding of the mechanism of NR1-mediated diabetic wound healing and provide a promising therapeutic drug to enhance diabetic wound healing.

Exposure to high concentrations of copper can cause toxic effects on the growth and development of organisms, but the relevant toxic mechanisms are far from fully understood. This study investigated the changes of metabolites, genes, and gut microorganisms in earthworms (Eisenia fetida) exposed to 0 (control), 67.58 (low), 168.96 (medium), and 337.92 (high) mg/kg of Cu in soil for 60 days. Differentially expressed genes (DEGs) and differential metabolites (DMs) at the low-, medium-, and high-level Cu exposure groups were identified and introduced into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Integrated metabolomic and transcriptomic analysis revealed that amino acid metabolism, lipid metabolism, and carbohydrate metabolism are the major metabolic pathways disturbed by Cu exposure. Furthermore, Cu exposure significantly decreased the diversity of the intestinal bacterial community and affected the relative abundance (increased or decreased) of intestinal colonizing bacteria. This resulted in high energy expenditure, inhibited nutrient absorption and fatty acid synthesis, and weakened antioxidant and detoxification abilities, ultimately inhibiting the growth of E. fetida. These findings offer important clues and evidence for understanding the mechanism of Cu-induced growth and development toxicity in E. fetida and provide further data for risk assessment in terrestrial ecosystems.

Self-healing hydrogels can repair their cracks, and restore their original properties. However, self-healing hydrogels usually face low mechanical strength and poor stability. By the dual crosslinking strategy, a self-healing hyaluronic acid-based hydrogel with enhanced strength was fabricated by dynamic acylhydrazone linkages between aldehyde-modified maleic sodium hyaluronate and 3,3'-dithiobis (propionylhydrazide) and subsequent photopolymerization among maleic groups in the hydrogel network. The hydrogels exhibit fast gelation and excellent self-healing capability due to the dynamic and reversible characteristics of acylhydrazone and disulfide linkages. Furthermore, the dual crosslinking increase the mechanical strength of the hydrogels and prolong their stabilization time. Swelling behaviors, morphology, and mechanical properties could be adjusted by altering the molar ratio of -NH-NH

As a complex and challenging complication for the patients with diabetes mellitus, diabetic ulcers are difficult to heal and current strategies cannot fulfill the patients' requirements. Pien Tze Huang (PZH) is a standardized medicine approved for various wounds treatments, and this study systematically investigated the effect and mechanism of intragastric administration of PZH (I-PZH) on diabetic wound healing.The effect of I-PZH on the healing of full-thickness wounds in rats with diabetes mellitus which was induced by high fat diet followed by streptozotocin injection was evaluated, and RNA sequencing (RNA-seq) and targeted central carbon metabolism metabolomics were combined to explore the underlying mechanism. I-PZH promoted wound healing, facilitated extracellular matrix synthesis, and maintained body weight of rats, but did not affect fasting blood glucose levels. Additionally, I-PZH significantly decreased 8-OHdG, cleaved caspase 3 and MMP9 levels, and increased TGF-β1 expression. RNA-seq analysis showed that I-PZH inhibited inflammation and that the vital common targets were TLR2, IL-17A and IL-1β; specifically affected "energy derivation by oxidation of organic compounds" with UQCRC1, NDUFS3 and SDHA as vital specific targets. Further experiments confirmed that I-PZH reduced TLR2, IL-17A and IL-1β, increased UQCRC1, SDHA, NDUFS3, promoted ATP synthesis and restored activity of mitochondrial respiratory chain complexes I and III in diabetic wounds. Metabolomics by HPLC-MS/MS analysis showed that I-PZH reversed multiple energy metabolism-related metabolites such as glucuronic acid, GMP, d-gluconic acid, cis-aconitic acid, ribose 5-phosphate and pantothenate.This study highlights the important role of inflammation and energy generation in diabetic wound healing, reveals wound repair mechanism of PZH and promotes its clinical application in diabetic wound treatment.

Myocardial infarction (MI) is a leading cause of mortality worldwide and it is urgent to discover effective therapies. In this study, the protective effect of salvianolic acid A (SAL) on MI induced by left anterior descending coronary artery ligation surgery and H2O2-induced H9c2 damage was evaluated. Rats were intraperitoneally injected with SAL once a day for 2 days before MI. At 24-h post-MI, the SAL-treated group showed significantly decreased infarct rate and enhanced myocardial function. Meanwhile, myocardial injury enzymes such as aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) were significantly reduced by SAL treatment. Taking advantage of RNA-seq technology, 52 disease targets of MI were associated with differentially expressed genes after SAL treatment in MI, among which 21 inflammation-related genes and 16 MAPK cascade-related genes were found. Further experiment indicated that SAL treatment reduced inflammatory factors such as IL-1β, IL-6, and TNF-α and decreased tunnel-positive cells and pro-apoptotic Bax after MI. Further investigation revealed that SAL treatment elevated thioredoxin (Trx) and inhibited the activation of c-jun N-terminal kinase (JNK) to attenuate apoptosis and inflammation after MI. Consistently, SAL protected cardiomyocytes against H2O2-induced H9c2 damage through increasing cell viability, decreasing cell apoptosis, and activating Trx and inhibiting JNK. Taken together, SAL inhibited cell apoptosis and inflammation through Trx/JNK signaling.

Background Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood. Aims We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). Methods We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT2 Profiler™ PCR array, and quantitative real-time PCR. The differential genes were subjected to Gene Ontology enrichment analysis and protein–protein interaction (PPI) network construction. Results Lipopolysaccharide profoundly aggravated the brain damage after 24 h post-MCAO. At the acute stage (ischemia/reperfusion 90 min/3 h), the brain homogenate gene expression of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and Interferon gamma-induced protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO + LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO + LPS group, which was also in an important position with degrees of ≥ 14 in PPI network. Conclusions It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 h post-MCAO.

Shengmai San Formula (SMS), composed of Ginseng Radix et Rhizoma, Ophiopogon Radix and Schisandra chinensis Fructus, was a famous formula in Tradition Chinese Medicine (TCM). With the expansion of clinical applications, SMS was developed to different dosage forms, including Shengmai Yin Oral liquid (SMY), Shengmai Capsule (SMC), Shengmai Granule (SMG), Shengmai Injection (SMI) and Dengzhan Shengmai Capsule (DZSMC). These above SMS-derived compound prescriptions (SSCPs) play an important role in the clinical treatment. This review is aimed to providing a comprehensive perspective of SSCP.The relevant literatures were collected from classical TCM books and a variety of databases, including PubMed, Google Scholar, Science Direct, Springer Link, Web of Science, China National Knowledge Infrastructure, and Wanfang Data.The chemical constituents of SSCPs, arrived from the individual medicinal materials including Ginseng Radix et Rhizoma, Ophiopogon Radix, Schisandra chinensis Fructus, Erigerontis Herba, were firstly summarized respectively. Then the pharmacokinetics studies, quality control, and pharmacological properties of SSCPs were all reviewed. The active compounds, pharmacokinetics characterizes, quality control markers, the effects and mechanisms of pharmacology of the different dosage forms of SSCPs were summarized. Furthermore, the research deficiencies of SSCPs and an innovative research paradigm for Chinese materia medica (CMM) formula were proposed.SMS, as a famous CMM formula, has great values in drug research and in clinical treatment especially for cardiocerebrovascular diseases. This article firstly make a comprehensive and systematic review on SMS.

Background: Viral pneumonia is one of the most serious respiratory diseases, and multicomponent traditional Chinese medicines have been applied in the management of infected patients. As a representative TCM, HouYanQing (HYQ) oral liquid shows antiviral activity. However, the unclear mechanisms, as well as the ambiguous clinical effects, limit widespread application of this treatment. Therefore, in this study, a proteomics-based approach was utilized to precisely investigate its efficacy.Methods: Based on the efficacy evaluation of HYQ in a mouse model of pneumonia caused by influenza A virus (H1N1) and the subsequent proteomics analysis, specific signatures regulated by HYQ treatment of viral pneumonia were identified.Results: Experimental verifications indicate that HYQ may show distinctive effects in viral pneumonia patients, such as elevated galectin-3-binding protein and glutathione peroxidase 3 levels.Conclusion: This study provides a precise investigation of the efficacy of a multicomponent drug against viral pneumonia and offers a promising alternative for personalized management of viral pneumonia.

Background: Cardiovascular disease is the leading cause of death worldwide and a major barrier to sustainable human development. The objective of this study was to evaluate the global, sex, age, region, and country-related cardiovascular disease (CVD) burden, as well as the trends, risk factors, and implications for the prevention of CVD.Methods: Detailed information from 1990 to 2017, including global, regional, and national rates of CVD, and 11 categories of mortality and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease Study 2017. The time-dependent change in the trends of CVD burdens was evaluated by annual percentage change.Results: More than 17 million people died from CVD in 2017, which was approximately two times as many as cancer, and increased nearly 50% compared with 1990. Ischemic heart disease and stroke accounted for 85% of the total age-standardized death rate (ASDR) of CVD. The ASDR and age-standardized DALYs rate (ASYR) of CVD were 1.5 times greater in men compared with women. People over the age of 50 were especially at risk for developing CVD, with the number of cases and deaths in this age group accounting for more than 90% of all age groups. CVD mortality was related to regional economic development and the social demographic index. In regions with a high economic income or socio-demographic index, there was a greater decline in the ASDR of CVD. The ASDR of CVD in high SDI regions decreased more than 50% from 1990 to 2017. Tobacco use, diets low in whole grains, diets high in sodium, and high systolic blood pressure were the important risk factors related to CVD mortality.Conclusions: CVD remains a major cause of death and chronic disability in all regions of the world. Ischemic heart disease and stroke account for the majority of deaths related to CVD. Although the mortality rate for CVD has declined in recent years from a global perspective, the results of CVD data in 2017 suggest that the mortality and DALYs of CVD varied in different ages, sexes, and countries/regions around the world. Therefore, it is necessary to elucidate the specific characteristics of global CVD burden and establish more effective and targeted prevention strategies.

Cell therapy is the frontier technology of biotechnology innovation and the most promising method for the treatment of refractory diseases such as tumours. However, cell therapy has disadvantages, such as toxicity and poor therapeutic effects. Plant extracts are natural, widely available, and contain active small molecule ingredients that are widely used in the treatment of various diseases. By studying the effect of plant extracts on cell therapy, active plant extracts that have positive significance in cell therapy can be discovered, and certain contributions to solving the current problems of attenuation and adjuvant therapy in cell therapy can be made. Therefore, this article reviews the currently reported effects of plant extracts in stem cell therapy and immune cell therapy, especially the effects of plant extracts on the proliferation and differentiation of mesenchymal stem cells and nerve stem cells and the potential role of plant extracts in chimeric antigen receptor T-cell immunotherapy (CAR-T) and T-cell receptor modified T-cell immunotherapy (TCR-T), in the hope of encouraging further research and clinical application of plant extracts in cell therapy.

Based on the actual test of the “1+1” UPS redundancy system, the causes of some abnormal data are analysed. Subsequently for the purpose of avoiding these abnormalities and improving power supply reliability, the key points are described. The park should pay attention to when to apply the “1+1” UPS redundancy system.

Biocontrol microbes are environment-friendly and safe for humans and animals. To seek biocontrol microbes effective in suppressing tomato gray mold is important for tomato production. Therefore, serial experiments were conducted to characterize the antagonism of Bacillus velezensis HY19, a novel self-isolated biocontrol bacterium, against Botrytis cinerea in vitro and the control on tomato gray mold in greenhouse. This bacterium produced extracellular phosphatase, protease, cellulose and siderophores, and considerably inhibited the growth of B. cinerea. A liquid chromatography-mass spectrometry (LC-MS) detected salicylic acid and numerous antifungal substances present in B. velezensis HY19 fermentation liquid (BVFL). When B. cinerea was grown on potato glucose agar, BVFL crude extract remarkably suppressed the fungal growth and reduced protein content and the activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD). Transcriptome studies showed that BVFL crude extract significantly induced different expression of numerous genes in B. cinerea, most of which were down-regulated. Theses differently expressed genes were involved in the biological process, cell compartment, molecular functions, and metabolisms of glycine, serine, threonine, and sulfur in pathogen hyphae. Thus, this biocontrol bacterium antagonized B. cinerea in multiple ways due to the production of numerous antifungal substances that acted on multiple targets in the cells. BVFL significantly increased antioxidant enzyme activities in tomato leaves and decreased the incidence of tomato gray mold, with the control efficacies of 73.12-76.51%. Taken together, B. velezensis HY19 showed a promising use potential as a powerful bioagent against tomato gray mold.