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Critical-sized maxillofacial bone defects have been a tough clinical challenge considering their requirements for functional and structural repair. In this study, an injectable in-situ forming double cross-linked hydrogel was prepared from gelatin (Gel), 20 mg/mL alginate dialdehyde (ADA), 4.5 mg/mL Ca

The emergence of single-cell RNA sequencing enables simultaneous sequencing of thousands of cells, making the analysis of cell population heterogeneity more efficient. In recent years, single-cell RNA sequencing has been used in the investigation of heterogeneous cell populations, cellular developmental trajectories, stochastic gene transcriptional kinetics, and gene regulatory networks, providing strong support in life science research. However, the application of single-cell RNA sequencing in the field of oral science has not been reviewed comprehensively yet. Therefore, this paper reviews the development and application of single-cell RNA sequencing in oral science, including fields of tissue development, teeth and jaws diseases, maxillofacial tumors, infections, etc., providing reference and prospects for using single-cell RNA sequencing in studying the oral diseases, tissue development, and regeneration.

Benzoquinone (BQ) is a desirable cathode for aqueous rechargeable batteries because of its high theoretical capacity and low cost. However, its application is seriously hindered by the high solubility of its discharge product in electrolytes, leading to rapid capacity decay. Here, we report a highly pyridine- and pyrrole-N-doped carbon cloth (NCC) with hierarchical pores as a promising host to anchor BQ and its discharge products. The resultant cathode (BQ-NCC) exhibits an ultrahigh initial capacity of 489 mA h gBQ−1 (excluding the capacity contribution of NCC) at 0.1 A g−1 and a long cycle life with a high capacity retention of 90.4% at 0.5 A g−1 after 500 cycles. Furthermore, a pouch-type cell with a capacity of ∼0.23 A h delivers an energy density of 136.1 W h kg−1 based on the total mass of BQ-NCC and Zn foil. Our study provides a novel strategy to construct high-performance aqueous Zn-ion batteries for potential practical applications.

Background Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions. Methods This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei. Results The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods. Conclusion Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.

Near fatal asthma is a life-threatening disorder that requires mechanical ventilation. Near fatal asthma and COPD with sudden cardiac arrest can worsen the outcomes. Previous studies demonstrated that ECMO is a live-saving measure for near fatal asthma that does not respond to traditional treatment.A patient with near fatal asthma (NFA) and COPD presented with high airway resistance, life-threatening acidemia and severe hypoxemia that failed to respond to conventional therapy. His hospital course was complicated by sudden cardiac arrest when preparing to initiate V-V mode extracorporeal membrane oxygenation (ECMO). The mode immediately changed from V-V to V-A, then to V-AV and finally to V-V mode in order to improve cardiac function and promote recovery of lung function.On the sixth day, ECMO was removed and on the ninth day, he was extubated and transferred to the ward. Finally, the patient was discharged home on the nineteenth day after admission to be followed up in the pulmonary clinic.The early application of ECMO and mode changing plausibly resulted in dramatic improvement in gas exchange and restoration of cardiac function. This case illustrates the critical role of ECMO mode changing as salvage therapy in NFA and COPD with sudden cardiac arrest.

How will the dual structural effects, represented by industrial structure and energy structure, affect the future correlation between economic growth and CO2 emissions? Taking Jilin Province as an example, this study explores the dynamic driving mechanism of dual structural effects on the correlation between economic growth and CO2 emissions by innovatively building an integrated simulation model from 1995 to 2015 and setting different scenarios from 2016 to 2050. Correspondingly, the concept of marginal utility and the method of variance decomposition analysis are introduced to reveal the mechanism. The results show that the energy structure is different while the industrial structure tends to be similar when CO2 emissions reach the peak under different scenarios. The slower the dual structure adjustment, the more significant the upward trend appears before the peak. The contribution of the dual structural effects to CO2 emissions caused by unit GDP growth is basically the same in peak year. With the transformation of socio-economy, the positive driving effect of the industrial structure will gradually weaken, while the negative driving effect of the energy structure will gradually increase. The methods and results presented can provide insights into sensible trade-offs of CO2 emissions and economic growth in different countries/regions during structural transitions.

Li-organic batteries (LOBs) are promising advanced battery systems because of their unique advantages in capacity, cost, and sustainability. However, the shuttling effect of soluble organic redox intermediates and the intrinsic dissolution of small-molecular electrodes have hindered the practical application of these cells, especially under high operating temperatures. Herein, a cross-linked membrane with abundant negative charge for high-temperature LOBs is prepared via electrospinning of poly(vinyl alcohol) containing halloysite nanotubes (HNTs). The translocation of negatively charged organic intermediates can be suppressed by the electronic repulsion and the cross-linked network while the positively charged Li

Cutaneous wound healing, especially diabetic wound healing, is a common clinical challenge. Reactive oxygen species (ROS) and bacterial infection are two major detrimental states that induce oxidative stress and inflammatory responses and impede angiogenesis and wound healing. A derivative of the metabolite itaconate, 4-octyl itaconate (4OI) has attracted increasing research interest in recent years due to its antioxidant and anti-inflammatory properties. In this study, 4OI-modified black phosphorus (BP) nanosheets are incorporated into a photosensitive, multifunctional gelatin methacrylamide hydrogel to produce a new photothermal therapy (PTT) and photodynamic therapy (PDT) system with antibacterial and antioxidant properties for diabetic wound regeneration. Under laser irradiation, the 4OI-BP-entrapped hydrogel enables rapid gelation, forming a membrane on wounds, and offers high PTT and PDT efficacy to eliminate bacterial infection. Without laser irradiation, BP acts as a carrier and controls the release of 4OI, with which it synergistically enhances antioxidant activity, thus alleviating excessive ROS damage to endothelial cells, promoting neovascularization, and facilitating faster diabetic wound closure. These findings indicate that 4OI-BP-entrapped multifunctional hydrogel provides a stepwise countermeasure with antibacterial and antioxidant properties for enhanced diabetic wound healing and may lead to novel therapeutic interventions for diabetic ulcers.

The study of screening active constituents from traditional Chinese medicine (TCM) is important for explicating the mechanism of action of TCM and further evaluating the safety and efficacy effectively. However, detecting and identifying the active constituents from complicated biological samples still remain a challenge. Here, a practical, quick, and novel integrated strategy from in vitro, in situ, in vivo to in silico for rapidly screening the active constituents was developed. Firstly, the chemical profile of TCM in vitro was identified using UPLC-Q Exactive-Orbitrap HRMS. Secondly, the in situ intestinal perfusion with venous sampling (IPVS) method was used to investigate the intestinal absorption components. Thirdly, after intragastric administration of the TCM extract, the in vivo absorbed prototype components were detected and identified. Finally, the target network pharmacology approach was applied to explore the potential targets and possible mechanisms of the absorbed components from TCM. The reliability and availability of this approach was demonstrated using Tongfengding capsule (TFDC) as an example of herbal medicine. A total of 141 compounds were detected and identified in TFDC, and among them, 64 components were absorbed into the plasma. Then, a total of 35 absorbed bioactive components and 50 related targets shared commonly by compounds and gout were integrated via target network pharmacology analysis. Ultimately, the effects of the absorbed components on metabolism pathways were verified by experiments. These results demonstrated that this original method may provide a practical tool for screening bioactive compounds from TCM treating particular diseases. Furthermore, it also can clarify the potential mechanism of action of TCM and rationalize the application of TFDC as an effective herbal therapy for gout.

A series of sodium polysulfides (SPSs) with different sulfur indexes was prepared as stabilizers to amend elemental mercury-contaminated artisanal small-scale gold mine (ASGM) tailings in Hubei, China, by controlling the molar ratio of sulfur and sodium sulfides as 1:1, 2:1, 3:1, and 4:1 during the synthesis. XRD, XPS, and laser Raman spectroscopy all suggested that the synthesized SPSs were a mixture of multiple polysulfides, sulfur, sodium sulfides, and sodium thiosulfate. Based on toxicity characteristic leaching procedure test (TCLP), mercury stabilization efficiency of SPSs was evaluated and proved to be more superior than sulfur, sodium sulfide, and also calcium polysulfide, with an optimal stabilization efficiency of 97.16% at SPS/THg = 1:2, SPSs pH = initial pH, and liquid-to-solid ratio = 20:7. A pseudo-second-order kinetic model was able to interpret the stabilization kinetics and demonstrated that mercury stabilization rate increased with the sulfur index in the SPSs, but excess SPSs were potentially to inhibit the precipitation of mercury. Speciation analysis results determined with sequential extraction indicated that the unstable mercury, elemental mercury, and organic-bound mercury fractions decreased respectively by up to 88.6%, 53.5%, and 26.3%. Pearson correlation analysis showed that the mercury stabilization in the mine tailings amended with SPSs mainly occurs from the precipitation of the elemental mercury, and the organic mercury fraction reduction was correlated with the decrease of the unstable mercury.

A type of thermally expandable microspheres (TEMs) for foam coating was prepared by suspension polymerization with acrylonitrile (AN), methyl methacrylate (MMA), vinyl acetate (VAC) as shell polymer monomers and i-pentane as core foaming agent. The effects of an aqueous additive (Sodium Chloride, NaCl) on the size and distribution of TEMs, and the effects of crosslinking degree, i-pentane dosage and monomer mass ratio on the expansion property, expansion temperature and solvent-resistance of TEMs were investigated. The results showed that when the dosage of NaCl was close to the saturation solubility (30%), the dosage of crosslinking agent and alkane were about 0.09% and 7.4%, and the mass ratio of AN/MMA/VAC w rm distribution and good solvent resistance, the expansion diameter ratio was 5 times under 110~120 C, which meets the application requirements for foam coating of leather or synthetic leather.

Synergistic therapy with high efficacy and low side effects is of great significance in cancer treatment, and therefore the elaborate design of advanced nanocarriers to benefit diverse loading requirements of size-varied therapy agents is of critical importance. Herein, we demonstrate a multifunctional drug carrier platform based on a hierarchical porous and -NH2-modified silica nanocarrier (FMSN) with a super high specific surface area and a large pore volume, which not only improves the loading capacity of both doxorubicin, a chemotherapeutic drug, and black phosphorus quantum dots (BPQDs), a kind of biocompatible photothermal agent, but also enhances the photothermal stability and biostability of the degradable BPQDs. The unique structure and surface design enable our multimodal platform with heat-stimulative, pH-responsive and sustained-release properties for chemo-photothermal synergistic cancer therapy. Both cytotoxicity experiments and in vivo study reveal that the combined therapy based on our multifunctional nanohybrids mediates the highest death rate of cancer cells compared to that of single chemotherapy or photothermal therapy. Our hierarchical mesoporous strategy provides an excellent drug delivery model for advanced chemo-photothermal synergistic targeted cancer therapy.

Based on compelling experimental and clinical evidence, the fruit of Lycium ruthenicum Murr. (LRM), a unique traditional Tibetan medicine, exerts beneficial effects on ameliorating learning and memory deficits of Alzheimer's disease (AD) and other neurodegenerative disorders. However, the potential active constituents and biological mechanism of LRM are still unknown. In this study, the major chemical constituents of LRM were first analyzed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). A total of 35 constituents were confirmed or tentatively identified. Furthermore, the network-based pharmacological strategy was applied to clarify the molecular mechanism of LRM on AD based on the identified components. Totally, 143 major targets were screened and supposed to be effective players in alleviating AD. Then, the LRM chemicals-major LRM putative targets-major pathways network was constructed, implying potential biological function of LRM on AD. More importantly, 12 core genes which can be modulated by LRM were identified, and they may play a pivotal role in alleviating some major symptoms of AD. This study provided a scientific basis for further investigation and application of LRM, which demonstrated that the network pharmacology approach could be a powerful way for the mechanistic studies of folk medicines.

Developing highly efficient heterogeneous catalysts for cycloaddition of CO2 and epoxides to produce cyclic carbonates is promising but challenging. In this work, a novel three-dimensional metal organic framework (MOF) with cylinder pore systems and unsaturated Zn sites has been demonstrated as potent candidate in CO2 fixation at mild and solvent-free conditions. The Zn(atz)(bdc)0.5, where atz = aminotriazole and H2bdc = terephthalic, exhibits microporous nature that can regulate the catalytic interaction of active centers and substrates. The structure stability has been systematically investigated and proven to be sufficient for practical application. Furthermore, the cooperative effects of porosity, CO2 binding affinity, activation centers, and synergism with co-catalyst have been deeply investigated. Moreover, high propylene epoxide conversion (97%) and selectivity (> 99%) have been achieved at mild conditions (60 °C and 1 MPa) with excellent cycle stability. Owing to the well-defined pore system, an obvious substrates selectivity has been clearly observed. A possible catalytic mechanism has been proposed and verified by DFT calculations. Furthermore, the prepared Zn-MOF can also be used as an efficient heterogeneous catalyst for the reaction of epoxides with alcohols to produce β-alkoxy alcohol.

Repairing infected bone defects is a challenge in the field of orthopedics because of the limited self-healing capacity of bone tissue and the susceptibility of refractory materials to bacterial activity. Innervation is the initiating factor for bone regeneration and plays a key regulatory role in subsequent vascularization, ossification, and mineralization processes. Infection leads to necrosis of local nerve fibers, impeding the repair of infected bone defects. Herein, a biomaterial that can induce skeletal-associated neural network reconstruction and bone regeneration with high antibacterial activity is proposed for the treatment of infected bone defects. A photosensitive conductive hydrogel is prepared by incorporating magnesium-modified black phosphorus (BP@Mg) into gelatin methacrylate (GelMA). The near-infrared irradiation-based photothermal and photodynamic treatment of black phosphorus endows it with strong antibacterial activity, improving the inflammatory microenvironment and reducing bacteria-induced bone tissue damage. The conductive nanosheets and bioactive ions released from BP@Mg synergistically improve the migration and secretion of Schwann cells, promote neurite outgrowth, and facilitate innerved bone regeneration. In an infected skull defect model, the GelMA-BP@Mg hydrogel shows efficient antibacterial activity and promotes bone and CGRP

The study of screening active constituents from traditional Chinese medicine (TCM) is important for explicating the mechanism of action of TCM and further evaluating the safety and efficacy effectively. However, detecting and identifying the active constituents from complicated biological samples still remain a challenge. Here, a practical, quick, and novel integrated strategy from in vitro, in situ, in vivo to in silico for rapidly screening the active constituents was developed. Firstly, the chemical profile of TCM in vitro was identified using UPLC-Q Exactive-Orbitrap HRMS. Secondly, the in situ intestinal perfusion with venous sampling (IPVS) method was used to investigate the intestinal absorption components. Thirdly, after intragastric administration of the TCM extract, the in vivo absorbed prototype components were detected and identified. Finally, the target network pharmacology approach was applied to explore the potential targets and possible mechanisms of the absorbed components from TCM. The reliability and availability of this approach was demonstrated using Tongfengding capsule (TFDC) as an example of herbal medicine. A total of 141 compounds were detected and identified in TFDC, and among them, 64 components were absorbed into the plasma. Then, a total of 35 absorbed bioactive components and 50 related targets shared commonly by compounds and gout were integrated via target network pharmacology analysis. Ultimately, the effects of the absorbed components on metabolism pathways were verified by experiments. These results demonstrated that this original method may provide a practical tool for screening bioactive compounds from TCM treating particular diseases. Furthermore, it also can clarify the potential mechanism of action of TCM and rationalize the application of TFDC as an effective herbal therapy for gout.

Background: The azygos lobe (AL) combined with partial anomalous pulmonary venous return (PAPVR) is comparatively uncommon as well as in radical surgery for right lung cancer.Case presentation: We herein present an extremely rare case of lung cancer coexisting with AL and asymptomatic PAPVC, which was diagnosed with preoperative contrast three-dimensional reconstruction and received radical surgery by thoracoscopy. During the surgery, we preserved azygos vein successfully and found a split type of PAPVR in right upper pulmonary vein.Conclusions: AL combined with PAPVR may cause confusion on the vascular separation and disconnection of the right pulmonary hilar. However, preoperative 3D reconstruction are more conducive to the correct performing of this type of surgery.

Background The azygos lobe (AL) combined with partial anomalous pulmonary venous return (PAPVR) is comparatively uncommon as well as in radical surgery for right lung cancer. Case presentation We herein present an extremely rare case of lung cancer coexisting with AL and asymptomatic PAPVR, which was diagnosed with preoperative contrast three-dimensional reconstruction and received radical surgery by thoracoscopy. During the surgery, we preserved azygos vein successfully and found a split type of PAPVR in right upper pulmonary vein. Conclusions AL combined with PAPVR may cause confusion on the vascular separation and disconnection of the right pulmonary hilar. However, preoperative 3D reconstruction is more conducive to the correct performing of this type of surgery.

Gamification of virtual rehabilitation devices gained rapid interest in the last two decades. Its popularity and use in remote telehealth and rehabilitation have gained more importance and application with the current COVID-19 pandemic situation. The benefits of gamification and the use of virtual reality (VR) games in rehabilitation therapy and telerehabilitation have been particularly well demonstrated in post-stroke patients. In this study, we present our pilot study using a game-based therapy approaches for the upper limb (UL) rehabilitation in elderly post-stroke patients in Singapore. The aim of the study is to develop a smart multi-sensory musical assistive system, called SilverTune, to promote the rehabilitation outcomes of elderly post-stroke patients. The SilverTune is like a musical instrument which is highly adaptable to provide six types of music audios and play interactions to cater for various elderly’s preferences and therapeutic movement requirements. SilverTune can also quantitatively record therapeutic data, analyze performance in real time, and give multi-modal feedback to both elderly and therapist. It is designed to produce a variety of digital audios like drum, saxophone, bell, harp, etc. via changing the shape and the interaction behaviours of the users. A SilverTune mobile app was developed as a companion mobile app for SilverTune music therapy. The app can play the digital contents, which is activated by SilverTune. Furthermore, the app can record user’s profile and the data input from SilverTune for future analysis by the therapist. Two games were developed to play using SilverTune device. The first is a horse racing game where the horse moves around a racetrack. The second is a table tennis game whereby the table tennis ball is required to be served across the net to gain points. The horse racing game facilitated shoulder flexion and extension, whereas the table tennis game facilitated shoulder horizontal abduction and adduction. If the movement of the SilverTunes device is detected by the accelerometer, the horse or bat will run or swing forward. If no movement is detected, then the horse or bat will be stationary. Participants’ self-perceived level of performance and satisfaction were shown to have significant improvements after the intervention phase. Particpants were also assessed before and after interventions using Fugl Meyer Assessment-Upper Extremity (FMA-UE), Canadian Occupational Performance Measure (COPM) scores with improvements in passive joint motion. Post-intervention questionnaire found that many participants liked SilverTune games due to its novelty, audio/visual effects and that it helped them to stay focused during therapy. SilverTune can be potentially used as a telerehabilitation tool for the current COVID-19 pandemic situation to support a safe high-quality care at a reduced cost.

Background Compensatory movements are commonly observed in older adults with stroke during upper extremity (UE) motor rehabilitation, which could limit their motor recovery. Aim This study aims to develop a compensation-aware virtual rehabilitation system (VRS) that can detect compensatory movements and improve the outcome of UE rehabilitation in community-dwelling older adults with stroke. Methods The VRS development includes three main components: (1) the use of thresholds for determining compensatory movements, (2) the algorithm for processing the kinematic data stream from Kinect to detect compensation in real-time, and (3) the audio-visual feedback to assist older adults with stroke to be aware of the compensation. Two studies were conducted following the VRS development, where Study 1 identified the value of thresholds for determining compensatory movements in two planar motor exercises, and Study 2 provided preliminary validation for the developed VRS by comparing two groups undergoing VR training or conventional training (CT) in a community rehabilitation center. Results The VRS could effectively detect all determined compensatory movements and timely trigger feedback in response to the detected compensatory movements. The VR participants showed significant improvements in Fugl-Meyer Assessment-Upper Extremity (FMA-UE, p = 0.045) and Wolf Motor Function Test (WMFT, p = 0.009). However, the VR and CT groups had no significant differences in outcome measures. Conclusion The VRS demonstrates the ability to detect compensation and the potential of assisting older adults with stroke to improve motor functions. Suggestions are given for further improvements of the VRS to support the older adult with stroke to reduce compensation.

Screening functional food ingredients (FFI) from medicinal and edible plants (MEP) has still remained a great challenge due to the complexity of MEP and its obscure function mechanisms. Herein, an integrated strategy based on sequential metabolites identification approach, network pharmacology, molecular docking, and surface plasmon resonance (SPR) analysis was proposed for quickly identifying the active constituents in MEP. First, the sequential biotransformation process of MEP, including intestinal absorption and metabolism, and hepatic metabolism, was investigated by oral gavage, and intestinal perfusion with venous sampling method. Then the blood samples were analyzed by UPLC-Q Exactive Orbitrap HRMS. Second, the network pharmacology approach was used to explore the potential targets and possible mechanisms of the in vivo metabolites of MEP. Third, molecular docking and SPR approaches were used to verify the specific interactions between protein targets and representative ingredients. The proposed integrated strategy was successfully used to explore the heptoprotective components and the underlying molecular mechanism of Paeoniae Radix Alba (PRA). A total of 44 compounds were identified in blood samples, including 17 porotypes and 27 metabolites. The associated metabolic pathways were oxidation, methylation, sulfation, and glucuronidation. After further screening, 31 bioactive candidates and 377 related targets were obtained. In addition, the bioactive components contained in PRA may have therapeutic potentials for non-alcoholic fatty liver disease (NAFLD). The above results demonstrated the proposed strategy may provide a feasible tool for screening FFI and elaborating the complex function mechanisms of MEP.

Zhiqiang Luo,1,* Guohua Yu,1,* Wubin Wang,1,* Rui Sun,1 Binbin Zhang,1 Jing Wang,2 Jing Liu,1 Shan Gao,1 Peng Wang,3 Yuanyuan Shi1,4 1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China; 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China; 3The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 4Shenzhen Research Institute, Beijing University of Chinese Medicine, Shenzhen, 518118, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng WangThe First Affiliated Hospital of Guangzhou Medical University, No. 151 Yanjiang Road, Yuexiu District, Guangzhou, 510120, People’s Republic of ChinaEmail mrwp0022@163.comYuanyuan ShiShenzhen Research Institute, Beijing University of Chinese Medicine, No. 16 Lanjingzhong Road, Pingshan District, Shenzhen, 518118, People’s Republic of ChinaTel +86 18565780299Email yshi@bucm.edu.cnIntroduction: Gu-Ben-Ke-Chuan (GBKC) decoction, a well-known prescription composed of seven herbs, has been widely used for treating chronic bronchitis (CB). However, the pharmacological constituents of GBKC and the underlying mechanisms by which these components act on CB remain unclear.Methods: Ultra-high-pressure liquid chromatography coupled with linear ion trap–Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) was first employed to rapidly identify compounds from GBKC. Thereafter, network pharmacology and molecular docking analyses were performed to identify the potential active constituents, candidate targets, and major pathways. Finally, the affinities between the key compounds and targets were verified via surface plasmon resonance (SPR) analysis. In addition, the anti-inflammatory effect of GBKC was verified using an LPS-induced inflammatory cell model based on the predicted results.Results: A total of 53 major compounds were identified in the GBKC decoction. After network pharmacology-based virtual screening, 141 major targets and 39 main compounds were identified to be effective in the treatment of CB. The major targets were highly enriched in the tumor necrosis factor (TNF) signaling pathway, suggesting that GBKC could attenuate the inflammatory response in patients with CB. Furthermore, molecular docking results indicated that 20 pairs of components and target proteins relevant to the TNF pathway exhibited notable interactions. Among them, eight compound-target pairs exhibited good affinity as per SPR analysis. In addition, the production of interleukin 6 and TNF-α in LPS-induced MH-S cells was suppressed after GBKC treatment.Conclusion: This study successfully clarified the mechanism of action of GBKC against CB, which demonstrated that the integrated strategy described above is reliable for identifying the active compounds and mechanisms responsible for the pharmacological activities of GBKC decoction.Keywords: Gu-Ben-Ke-Chuan decoction, chronic bronchitis, UHPLC-LTQ-Orbitrap, network pharmacology, surface plasmon resonance

Oracle-bone-script, a type of writing on tortoise shells or animal bones. Aiming at the complex structure and changeable forms of oracle-bone-script fonts, this paper designs a virtual teaching machine system of oracle-bone-script (VTMS), which realizes the dynamic decomposition and demonstration of oracle-bone-script character structure. This system uses the dynamic description technology of Chinese character structure. Simultaneously, TTS and natural language generation technologies are applied in this system to implement the voice prompts and navigation functions of oracle-bone-script. The system presents oracle-bone-script related content on Web and mobile app, so it is necessary to coordinate with the architecture of the server. The experimental results show that the VTMS is practical, which sheds new light on interactive teaching software based on virtual teaching robot system.

Venenum Bufonis (VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components–main HF putative targets–main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.

Intervertebral disc degeneration (IVDD) is a main cause of low back pain that is associated with extracellular matrix (ECM) degradation and inflammation. This study aims to investigate the role of DNMT3B and its regulatory mechanisms in IVDD. IVDD rat models were constructed followed by transfections with oe-DNMT3B or oe-YAP in order to explore the role of DNMT3B in the development of IVDD. After that transfection, nucleus pulposus (NP) cells were isolated and transfected with oe-DNMT3B, oe-TRPA1, si-YAP, oe-YAP or oe-COX2 in order to investigate the functions of DNMT3B in NP cells. DNMT3B was poorly expressed in IVDD tissues and NP cells whereas TRPA1, COX2, and YAP were highly expressed. The proliferation or apoptosis of NP cells was detected through CCK-8 assay or flow cytometry, respectively. Overexpression of DNMT3B promoted the proliferation of NP cells, inhibited their apoptosis, as well as increasing the expression of collagen II and aggrecan and decreasing expression of MMP3 and MMP9. Besides, DNMT3B suppressed inflammation and alleviated IVDD. Mechanistically, DNMT3B modified the TRPA1 promoter by methylation to inhibit the expression of COX2. Overexpression of COX2 promoted the apoptosis of NP cells and decreased the expression of YAP, which was reversed by upregulating DNMT3B. DNMT3B may promote the proliferation of NP cells and prevent their ECM degradation through the TRPA1/COX2/YAP axis, thereby alleviating IVDD in rats.

A new round of electricity market reform has been carried out in China since 2015. Due to the spatial mismatch of electricity supply and demand in China, inter-provincial electricity market will occupy an important position in the electricity market system in China. The experience of European unified electricity market provides inspirations for the construction of the national electricity market in China. In this paper, European unified electricity market is introduced, including the day-ahead market coupling mechanism and corresponding market clearing algorithm. The enlightenment of European experience to China is analyzed, from mechanism design to technique implementations. Then, an inter-provincial electricity spot market model is proposed for the national unified electricity market in China, and the market clearing algorithm is designed. Based on the proposed model, energy flow and cash flow of the national market are analyzed. Case study based on a 19-bus system shows the effectiveness of the proposed model.

Aligned GaN nanowire arrays show great potential not only in optoelectronic devices, but also in sensitive biosensor applications, owing to their excellent chemical stability and biocompatibility, as well as high electron mobility and surface-to-volume ratio. However, to construct electrochemical immunosensors, proper surface modification of GaN nanowires, which can enable efficient charge transfer and provide large densities of immobilization sites for antibodies to anchor, is still challenging. Herein we demonstrate a highly sensitive label-free electrochemical immunosensing platform based on the integration of polydopamine (PDA) on a GaN nanowire surface. The PDA polymer was self-assembled on GaN nanowire surfaces via organic polymerization. The interface dipole layer generated at the GaN nanowire array/PDA polymer heterointerface enabled efficient charge transfer. The aligned GaN nanowire array/PDA hybrids were further modified with gold nanoparticles for subsequent covalent binding of antibodies. The fabricated immunosensor yielded a wide linear range between 0.01 and 100 ng ml-1 and a detection limit as low as 0.003 ng ml-1 for the detection of alpha-fetoprotein (AFP). The immunosensor showed good selectivity, reproducibility, and stability and was utilized in human serum samples for AFP detection. This work demonstrates the superiority of taking advantage of a nanowire array configuration and a semiconductor/polymer heterointerface in an immunosensing platform for sensitivity enhancement.

Introduction: Current studies estimated a general incubation period distribution of COVID-19 based on early-confirmed cases in Wuhan, and have not examined whether the incubation period distribution varies across population segments with different travel histories. We aimed to examine whether patients infected by community transmission had extended incubation periods than the early generation patients who had direct exposures to Wuhan. Methodology: Based on 4741 patient case reports from municipal centers of disease control by February 21, 2020, we calculated the incubation periods of 2555 patients with clear epidemiological survey information and illness development timeline. All patients were categorized into five groups by their travel histories. Incubation period distributions were modeled for each group by the method of the posterior Weibull distribution estimation. Results: Adults aged 30 to 59 years had the most substantial proportion of confirmed cases in China. The incubation period distribution varied slightly across patient groups with different travel histories. Patients who regularly lived in Wuhan and left to other locations before January 23, 2020 had the shortest posterior median value of 7.57 days for the incubation period, while the incubation periods for persons affected by local community transmission had the largest posterior median of incubation periods, 9.31 days. Conclusions: The median incubation period for all patients infected outside Wuhan was 9 days, a bit of more extended than the early estimated 5-day incubation period that was based on patients in Wuhan. Our findings may imply the decreases of virulence of the COVID-19 virus along with intergenerational transmission.

Mn3O4 is viewed as an attractive candidate for rechargeable aqueous zinc-ion battery cathode materials due to the advantages of low cost, eco-friendly nature as well as high capacity. However, it faces inherently poor electronic conductivity and poor cyclability during battery cycling. To improve the electrochemical performance, Mn3O4 nanoparticles anchored on carbon nanotubes (CNTs@Mn3O4) were fabricated by a facile one-step solution process at low temperature. Benefiting from the synergistic effect of nanoscale Mn3O4 and 1D CNTs, the conductivity and electrochemical performance of Mn3O4 are significantly improved. The prepared CNTs@Mn3O4 nanocomposites deliver a discharge capacity of 310 mAh g-1 at 100 mA g-1, and maintain 123 mAh g-1 at 1000 mA g−1 after 500 cycles, demonstrating good rate capability and cycling performance as a promising cathode material for low-cost neutral zinc-ion battery.

Flexible and adhesive hydrogels with self-healing abilities have great potential in various fields. In the present study, a new type of self-healing and adhesive hydrogel driven by noncovalent interactions including hydrogen bonds and hydrophobic interactions was readily constructed by mixing lignosulfonate (LS) and polyvinylpyrrolidone (PVP) in water. When the pH value was adjusted to neutral, LS aggregated to form rigid noncovalent junctions and PVP associated with these domains to form a flexible network. A series of hydrogels were obtained by altering the concentrations of LS and PVP. Owing to the unique structure and dynamic and reversible characteristics of the gelation mechanism, the hydrogel exhibited good toughness, and self-healing ability. The abundant active groups and improved cohesion endowed the LS/PVP composite (LPC) hydrogel with good adhesive ability to various substrates. In addition, the LPC hydrogel exhibited excellent biocompatibility. Collectively, these advanced properties allowed the hydrogel to be successfully applied as a hemostatic agent to treat organ injuries. This work provides a new platform for multifunctional lignin-based hydrogel which could be applied in biomaterials.

Conductive hydrogels based on pure-phase conductive polymers have great promise in bioelectronic device and energy device application. However, commonly-used crosslinking agents for conductive polymers, such as phytic acid (PA), have low conductivities and therefore limit the improvement in the conductivity of conductive polymer hydrogels (CPHs). Herein, we explore a general approach using PEDOT:PSS as conductive dopant to crosslink various conductive polymers, including polyaniline (PAni), polypyrrole (PPy), and Poly-aminoindole (PIn-X-NH2, X = 4, 5, 6, 7). The synthesis mechanism of the conductive hydrogels is based on the electrostatic interaction between negatively charged SO3- groups in PEDOT:PSS and positively charged PAni, PPy, PIn-X-NH2 polymer chains. In comparison with the CPHs crosslinked with PA, the CPHs crosslinked with PEDOT:PSS have much higher conductivities and greatly improved biocompatibilities, which are highly demanded for bioelectronics application. The CPHs crosslinked with PEDOT:PSS are demonstrated to serve as electroactive interfacial materials for in situ electrochemical sensing of bioactive molecules, such as dopamine and hydrogen peroxide, released from living cells. Our novel strategy for the fabrication of CPHs with commercially available PEDOT:PSS as conductive crosslinking dopant would provide great opportunities in the construction of highly conductive hydrogels for versatile applications in bioelectronics and energy devices.

Natural bone is a highly vascularized tissue that relies on the vasculature for blood and nutrients supply to maintain skeletal integrity. Bioactive nanomaterials with the capability of improving vascularized bone regeneration are highly demanded for bone tissue engineering. In this work, 2D silicon phosphorus (SiP) is explored as a new kind of bioactive and biodegradable nanomaterial with excellent angiogenesis and osteogenesis, and a 3D printed biohybrid hydrogel of GelMA-PEGDA incorporated with photocrosslinkable SiP-nanosheet (GelMA-PEGDA/SiPAC) is developed to apply on bone tissue engineering. Findings show that the GelMA-PEGDA/SiPAC possessess excellent biocompatibility and biodegradability, and can sustainably release Si and P elements. Compared with the biohybrid hydrogel scaffolds incorporated with black phosphorus nanosheets, the GelMA-PEGDA/SiPAC can further enhance the osteogenesis of mesenchymal stem cells, and tubular networking of human umbilical vascular endothelial cells. In a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by GelMA-PEGDA/SiPAC have been confirmed in vivo. The current strategy paves a new way to design a multifunctional SiP nanocomposite scaffold on mediating the osteogenesis and angiogenesis in one system, and provides a bioactive and biodegradable alternative nanomaterial for tissue engineering and regenerative medicine.