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Microparticles have demonstrated value for regenerative medicine. Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration. Here, inspired by erythrocytes-associated self-repairing process in damaged tissue, we present novel biomimetic erythrocyte-like microparticles (ELMPs). These ELMPs, which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus, hemoglobin, and growth factors (GFs), are generated by using a microfluidic electrospray. As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen, they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion, stimulating angiogenesis, and adjusting the release profile of cargoes. Based on these features, we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration. Thus, we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.

Abstract Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.

Sarcopenia is an age-related condition characterized by the progressive loss of skeletal muscle mass and strength. With the global aging population, its incidence is rapidly increasing. Lipid peroxidation is a critical biochemical process that generates reactive oxygen species (ROS), leading to the destruction of muscle cell structure and function. It plays a pivotal role in the onset and progression of sarcopenia. This review summarizes the mechanisms by which lipid peroxidation contributes to sarcopenia, with a focus on its regulatory effects on cell membrane damage, mitochondrial dysfunction, and cell death. In addition, we discuss the protective role of antioxidant factors such as GPX4 (glutathione peroxidase 4) and antioxidant peptides like SS peptides in mitigating lipid peroxidation and delaying the progression of sarcopenia. Finally, the potential of various strategies, including natural compounds, supplements, natural extracts, and lifestyle interventions, in inhibiting lipid peroxidation and promoting muscle health is explored.

Abstract Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair. Graphical Abstract

Abstract Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Herein, the lasing action of fabricated bulged CH3NH3PbBr3 microwires is demonstrated with features of a low threshold, narrow linewidth, single‐mode operation, and high intensity. Benefiting from the bulged end facets, the CH3NH3PbBr3 microwires are feasible for constructing a high‐brightness, whispering‐gallery‐mode(WGM)‐type, and single‐mode laser while suppressing Fabry–Pérot‐type multi‐mode lasing. Numerical simulation unveils that the bulged end facets result in the significantly reduced reflectivity of fundamental waveguided modes. The obtained microlasers require neither complex structures (such as distributed Bragg reflector) nor careful pumping adjustment, suggesting the practical feasibility of a higher single‐mode lasing intensity than conventional WGM perovskite microlasers. The results provide new routes to realize high‐performance perovskite microlasers and their potential application in sensing refractive index.

Abstract The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Abstract Objective To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery. Methods We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months. Results All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100–145). Median estimated blood loss was 224 ml (IQR: 190–255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P

Abstract Microfibers from natural products are endowed with remarkable biocompatibility, biodegradability, sustainable utilization as well as environmental protection characteristics etc. Benefitting from these advantages, microfibers have demonstrated their prominent values in biomedical applications. This review comprehensively summarizes the relevant research progress of sustainable microfibers from natural products and their biomedical applications. To begin, common natural elements are introduced for the microfiber fabrication. After that, the focus is on the specific fabrication technology and process. Subsequently, biomedical applications of sustainable microfibers are discussed in detail. Last but not least, the main challenges during the development process are summarized, followed by a vision for future development opportunities.

Abstract Anticoagulation is vital to maintain blood fluidic status and physiological functions in the field of clinical blood‐related procedures. Here, novel biomimetic anticoagulated porous inverse opal hydrogel particles is presented as anticoagulant bearing dynamic screening capability. The inverse opal hydrogel particles possess abundant sulfonic and carboxyl groups, which serve as binding sites with multiple coagulation factors and inhibit the blood coagulation process. Owing to the variations of refractive index and pore sizes during the binding process, the particles appeared corresponding structure color variations, which can be adopted as sensory index of anticoagulation. Based on these features, a sensor containing these diverse structure color particle units is constructed for pattern recognition of coagulation factors level in clinical plasma samples. By analyzing the sensory information of the unit, the colorimetric “fingerprint” for each target can be obtained and summarized as a database. Besides, a portable test‐strip integrating sensory units is developed to distinguish the sample regarding abnormal coagulation factors‐derived diseases via multivariate data analysis. It is believed that such biomimetic anticoagulated structural color particles and their derived sensor will open new avenue for clinical detection and disease diagnosis.

As a new kind of microcarrier device, microneedles are featured by micrometer needle arrays with an overall size in the centimeter scale. Due to the needle shape and the micron size, microneedles can penetrate the skin without harming nerves and blood vessels, which causes many advantages such as minimally invasive, safe and convenient. The past few decades have witnessed a great leap in microneedles research. The main materials of microneedles have changed from metal and ceramic to polymers with more complex functions, and the optimization of materials and preparation strategies has led to a greater variety of microneedle styles. Among them, the construction or combination of smaller size structures or materials on microneedles to fabricate hierarchical microneedles is a major research hotspot. Here, we present the recent research progress of hierarchical microneedles for biomedicine. We begin by discussing the fabrication strategies of hierarchical microneedles, including mainstream casting and coating methods based on microneedle molds and three dimensions (3D) printing methods. We then expand the discussion from the hierarchical microneedles with porous structure to those composited with nanomaterials. Eventually, we have a discussion about the research progress of hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery, as well as its future development direction.

The low inertia characteristic of the power system is increasingly prominent with the increase of wind power penetration. Therefore, the threat of random wind speeds and sudden frequency events to the frequency stability of a low inertia power system is further enhanced. It is necessary for wind power generators to provide frequency auxiliary service for the power system through appropriate control schemes. To address these issues, a frequency control scheme is proposed for a doubly-fed induction generator (DFIG) to support the frequency stability of the system in this paper, which can play a role in additional-loop-based frequency smooth control (FSC) and dynamic inertial control (DIC) by a smooth switcher. The objective of FSC is to smooth the frequency fluctuation caused by random wind speeds, load fluctuation, etc., while DIC aims at improving the frequency nadir (FN) and simultaneously preventing rotor speed over-deceleration during a large disturbance. In addition, a smooth switcher is proposed to coordinate the advantages of FSC and DIC. Note that the proposed approach can be automatically switched from FSC to DIC, while frequency deviation exceeds the given threshold due to a large disturbance. Finally, simulation results on the IEEE 14-bus system show the advantages of the proposed method in improving frequency stability under real complex situations while ensuring the stable operation of wind turbine generators.

As a low-cost and high-efficiency distributed energy storage resource, electric vehicles (EVs) play an increasingly prominent role in power system regulation. Since EVs are the regulation resources on the demand side, EVs should return to the initial states as soon as possible after completing the grid regulation task to avoid affecting the charging demand. Although EVs can provide a more flexible response to under-frequency load shedding (UFLS) than load shedding, the disorderly recharging of EVs during the load restoration stage may cause a significant second disturbance to the system frequency after UFLS. To ensure frequency stability and simultaneously restore the power supply, a multi-stage sequential load restoration method for UFLS with EVs participation is proposed to coordinate the priority and sequential restoration between the shedding load and recharging power of EVs. In the proposed method, the restoration willingness of EVs is quantified by the membership function, and the EV recharging optimization model with the objective function of maximizing the user’s restoration willingness satisfaction is established based on a two-stage robust under-frequency load shedding framework. Simulation results show that the proposed method can ensure system frequency stability and complete the load restoration quickly, effectively avoiding the secondary frequency drop caused by the disorderly recharging of EVs.

BackgroundPrevious studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate.MethodsWe conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings.ResultsWe identified potential associations between erysipelas and various gut microbiota, including Alcaligenaceae (OR 1.23; 95% CI 1.06-1.43; p=0.006), Rikenellaceae (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with Actinomyces, Lachnospiraceae NC2004 group, Ruminiclostridium 9, Ruminococcaceae UCG014, Odoribacter, and Actinobacteria were also observed. Sensitivity analyses confirmed the robustness of these associations.ConclusionOur MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.

In response to challenges such as narrow visibility for ship navigators, limited field of view from a single camera, and complex maritime environments, this study proposes panoramic visual perception-assisted navigation technology. The approach includes introducing a region-of-interest search method based on SSIM and an elliptical weighted fusion method, culminating in the development of the ship panoramic visual stitching algorithm SSIM-EW. Additionally, the YOLOv8s model is improved by increasing the size of the detection head, introducing GhostNet, and replacing the regression loss function with the WIoU loss function, and a perception model yolov8-SGW for sea target detection is proposed. The experimental results demonstrate that the SSIM-EW algorithm achieves the highest PSNR indicator of 25.736, which can effectively reduce the stitching traces and significantly improve the stitching quality of panoramic images. Compared to the baseline model, the YOLOv8-SGW model shows improvements in the P, R, and mAP50 of 1.5%, 4.3%, and 2.3%, respectively, its mAP50 is significantly higher than that of other target detection models, and the detection ability of small targets at sea has been significantly improved. Implementing these algorithms in tugboat operations at ports enhances the fields of view of navigators, allowing for the identification of targets missed by AISs and radar systems, thus ensuring operational safety and advancing the level of vessel intelligence.

Gouty arthritis (GA) is an inflammatory disease characterized by pain. The primary goal of current treatment strategies during GA flares remains the reduction of inflammation and pain. Research suggests that the gut microbiota and microbial metabolites contribute to the modulation of the inflammatory mechanism associated with GA, particularly through their effect on macrophage polarization. The increasing understanding of the gut-joint axis emphasizes the importance of this interaction. The primary objective of this review is to summarize existing research on the gut-immune-joint axis in GA, aiming to enhance understanding of the intricate processes and pathogenic pathways associated with pain and inflammation in GA, as documented in the published literature. The refined comprehension of the gut-joint axis may potentially contribute to the future development of analgesic drugs targeting gut microbes for GA.

Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus. Compared to traditional diabetes treatments, cell therapy can restore endogenous insulin supplementation, but its large-scale clinical application is impeded by donor shortages, immune rejection, and unsuitable transplantation sites. To overcome these challenges, an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes. This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy, including different cell sources encapsulated in hydrogels, encapsulation methods, hydrogel types, and a series of accessorial manners to improve transplantation outcomes. In addition, the formation and application challenges as well as prospects are also presented.

Hydrogel microparticles have been proved to be curative to diabetic wounds. Current trends focus on the integration of bioactive matrix and their smart stimulus-responsive release to meet the complex demand of regeneration in diabetic wound. In this paper, we present novel stem cell exosome-encapsulated Chinese herb glycyrrhizic acid (GA) hydrogel microparticles for wound healing. The integrated GA endows the hydrogel microparticles with antibacterial properties, while the encapsulated exosomes impart them with pro-angiogenesis ability. In addition, as the black phosphorus is incorporated into these hybrid hydrogel microparticles, the release profile of GA and exosomes could be controllable under near-infrared irradiation due to the excellent photothermal effect of black phosphorus and the reversible phase transformation properties of GA. Based on these features, we have demonstrated that these microparticles can effectively kill bacteria, scavenge free radical, and promote angiogenesis from in vitro experiments. Besides, they could also markedly accelerate the wound healing process by down-regulating inflammation and promoting collagen deposition and angiogenesis in bacteria-infected in vivo diabetic wound. These results indicate that the proposed exosome-integrated GA hydrogel microparticles present great potential for clinical diabetic wound treatment.

BackgroundGastroduodenal ulcers are associated with Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear.MethodsWe conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings.ResultsOur study showed that the abundance of Enterobacteriaceae, Butyricicoccus, Candidatus Soleaferrea, Lachnospiraceae NC2004 group, Peptococcus, and Enterobacteriales was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of Streptococcaceae, Lachnospiraceae UCG010, Marvinbryantia, Roseburia, Streptococcus, Mollicutes RF9, and NB1n was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer.ConclusionThis study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.

BackgroundPrevious research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between appendicitis and the gut microbiota remains an unresolved and contentious issue.MethodsIn this investigation, we performed a Mendelian randomization (MR) analysis employing publicly accessible summary data extracted from genome-wide association studies (GWAS) to elucidate the potential causal nexus between the gut microbiota and the development of appendicitis. We initially identified instrumental variables (IVs) through a comprehensive array of screening methodologies, subsequently executing MR analyses using the Inverse Variance Weighted (IVW) technique as our primary approach, supplemented by several alternative methods such as MR Egger, weighted median, simple mode, and weighted mode. Additionally, we implemented a series of sensitivity analysis procedures, encompassing Cochran’s Q test, MR-Egger intercept test, Mendelian Randomized Polymorphism Residual and Outlier (MR-PRESSO) test, and a leave-one-out test, to affirm the robustness and validity of our findings.ResultsOur investigation indicates that an elevated prevalence of Deltaproteobacteria, Christensenellaceae, Desulfovibrionaceae, Eubacterium ruminantium group, Lachnospiraceae NK4A136 group, Methanobrevibacter, Desulfovibrionales, and Euryarchaeota is inversely associated with the risk of appendicitis. Conversely, we observed a positive correlation between an increased abundance of Family XIII, Howardella, and Veillonella and the susceptibility to appendicitis. Sensitivity analyses have corroborated the robustness of these findings, and Mendelian randomization analyses provided no indications of reverse causality.ConclusionOur Mendelian randomization (MR) analysis has unveiled potential advantageous or detrimental causal associations between the gut microbiota and the occurrence of appendicitis. This study offers novel theoretical and empirical insights into the understanding of appendicitis pathogenesis, along with its implications for preventive and therapeutic strategies.

AbstractBackground The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood.Methods We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs.Results We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (p = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs.Conclusion The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.

Abstract 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.

Natural biomaterials have been widely applied in wound treatment. Hotspots in this area are focused on reducing their immunogenicity and improving their therapeutic effect. In this work, we present a novel aquaculture derived hybrid skin patch based on acellular fish skin (AFS) and chitosan (CS) for wound healing. Such functional patch was simply constructed by infiltrating the vascular endothelial growth factor (VEGF)-loaded CS pregel into the porous scaffold of the AFS. As the natural molecules and structure of fish skin are well-retained during the synthesis processes, the final patch presented brilliant tensile property, water-absorption property, good biocompatibility and low immunogenicity. In addition, the integrated CS and VEGF endow the patch with antibacterial and angiogenesis capability respectively for promoting tissue growth and wound healing. Thus, in a full-thickness wound rat model, the hybrid patch has been demonstrated with dramatic therapeutic efficacy in inhibiting inflammatory, accelerating angiogenesis, collagen deposition, and tissue generation during the wound repair procedure. These features imply the practical value of this multifunctional aquaculture derived hybrid skin patch in clinical wound management.

Abstract Chimeric antigen receptor T (CAR-T) cell targeting CD19 antigen has achieved exhilarative clinical efficacy in B-cell malignancies. However, challenges still remain for the currently approved anti-CD19 CAR-T therapies, including high recurrence rates, side effects and resistance. Herein, we aim to explore combinatorial therapy by use of anti-CD19 CAR-T immunotherapy and gallic acid (GA, an immunomodulatory natural product) for improving treatment efficacy. We assessed the combinatorial effect of anti-CD19 CAR-T immunotherapy with GA in cell models and a tumor-bearing mice model. Then, the underlying mechanism of GA on CAR-T cells were investigated by integrating network pharmacology, RNA-seq analysis and experimental validation. Furthermore, the potential direct targets of GA on CAR-T cells were explored by integrating molecular docking analysis with surface plasmon resonance (SPR) assay. The results showed that GA significantly enhanced the anti-tumor effects, cytokine production as well as the expansion of anti-CD19 CAR-T cells, which may be mainly through the activation of IL4/JAK3-STAT3 signaling pathway. Furthermore, GA may directly target and activate STAT3, which may, at least in part, contribute to STAT3 activation. Overall, the findings reported here suggested that the combination of anti-CD19 CAR-T immunotherapy with GA would be a promising approach to increase the anti-lymphoma efficacy.

Abstract Hyaluronic acid (HA) is an attractive extracellular matrix‐derived polymer. The related HA‐based hydrogels are emerging to be the hotspots in the cutting edge of biomaterials. The continuous sights concentrate on exploring modification methods and crosslinking strategies to promote the advancement of HA‐based hydrogels with enhanced physical/chemical properties and enriched biological performance. Here, the advances on modification methods and crosslinking strategies for fabricating HA‐based hydrogels with diverse capacities are summarized. Firstly, the modification reactions that occur on the active hydroxyl, carboxyl and N‐acetyl groups of HA molecule are discussed. Next, the emphasis is put on various crosslinking strategies including physical crosslinking, covalent crosslinking and dynamic covalent crosslinking. Finally, we provide a general summary and give a critical viewpoint on the remaining challenges and the future development of HA‐based hydrogels. It is hoped that this review can provide new proposals for the specific design of functional hydrogel biomaterials.

Angiogenesis and neurogenesis play irreplaceable roles in bone repair. Although biomaterial implantation that mimics native skeletal tissue is extensively studied, the nerve-vascular network reconstruction is neglected in the design of biomaterials. Our goal here is to establish a periosteum-simulating bilayer hydrogel and explore the efficiency of bone repair via enhancement of angiogenesis and neurogenesis. In this contribution, we designed a bilayer hydrogel platform incorporated with magnesium-ion-modified black phosphorus (BP) nanosheets for promoting neuro-vascularized bone regeneration. Specifically, we incorporated magnesium-ion-modified black phosphorus (BP@Mg) nanosheets into gelatin methacryloyl (GelMA) hydrogel to prepare the upper hydrogel, whereas the bottom hydrogel was designed as a double-network hydrogel system, consisting of two interpenetrating polymer networks composed of GelMA, PEGDA, and β-TCP nanocrystals. The magnesium ion modification process was developed to enhance BP nanosheet stability and provide a sustained release platform for bioactive ions. Our results demonstrated that the upper layer of hydrogel provided a bionic periosteal structure, which significantly facilitated angiogenesis via induction of endothelial cell migration and presented multiple advantages for the upregulation of nerve-related protein expression in neural stem cells (NSCs). Moreover, the bottom layer of the hydrogel significantly promoted bone marrow mesenchymal stem cells (BMSCs) activity and osteogenic differentiation. We next employed the bilayer hydrogel structure to correct rat skull defects. Based on our radiological and histological examinations, the bilayer hydrogel scaffolds markedly enhanced early vascularization and neurogenesis, which prompted eventual bone regeneration and remodeling. Our current strategy paves way for designing nerve-vascular network biomaterials for bone regeneration.

Abstract Background Wound healing has become a worldwide healthcare issue. Attempts in the area focus on developing patches with the capabilities of avoiding wound infection, promoting tissue remolding, and reporting treatment status that are of great value for wound treatment. Results In this paper, we present a novel inverse opal film (IOF) patch based on a photo-crosslinking fish gelatin hydrogel with the desired features for wound healing and dynamic monitoring. The film with vibrant structure colors was constructed by using the mixture of fish gelatin methacryloyl, chitosan, and polyacrylic acid (PAA) to replicate colloidal crystal templates. As the structures of these natural biomolecules are well-retained during the fabrication, the resultant IOF was with brilliant biocompatibility, low immunogenicity, antibacterial property, as well as with the functions of promoting tissue growth and wound healing. In addition, the IOF presented interconnected nanopores and high specific surface areas for vascular endothelial growth factor loading, which could further improve its angiogenesis capability. More attractively, as the pH-responsive PAA was incorporated, the IOF patch could report the wound healing status through its real-time structural colors or reflectance spectra. Conclusions These features implied the practical value of the multifunctional fish gelatin hydrogel IOFs in clinical wound management. Graphical Abstract

Abstract 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.

Abstract Chemotherapy is an essential postoperative treatment for pancreatic cancer, while due to the lack of effective drug evaluation platforms, the therapeutic outcomes are hampered by tumor heterogeneity among individuals. Here, a novel microfluidic encapsulated and integrated primary pancreatic cancer cells platform is proposed for biomimetic tumor 3D cultivation and clinical drug evaluation. These primary cells are encapsulated into hydrogel microcapsules of carboxymethyl cellulose cores and alginate shells based on a microfluidic electrospray technique. Benefiting from the good monodispersity, stability, and precise dimensional controllability of the technology, the encapsulated cells can proliferate rapidly and spontaneously form 3D tumor spheroids with highly uniform size and good cell viability. By integrating these encapsulated tumor spheroids into a microfluidic chip with concentration gradient channels and culture chambers, dynamic and high‐throughput drug evaluation of different chemotherapy regimens could be realized. It is demonstrated that different patient‐derived tumor spheroids show different drug sensitivity on‐chip, which is significantly consistent with the clinical follow‐up study after the operation. The results demonstrate that the microfluidic encapsulated and integrated tumor spheroids platform has great application potential in clinical drug evaluation.

Introduction: Holt–Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS.Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3′-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells.Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.

Abstract Structural colors materials are profoundly explored owing to their fantastic optical properties and widespread applications. Development of structural color materials bearing flexible morphologies and versatile functionalities is highly anticipated. Here, a droplet‐confined, magnetic‐induced self‐assembly strategy for generating rotary structural color spindles (SCSPs) by fast solvent extraction is proposed. The as‐prepared SCSPs exhibit an orderly close‐packed lattice structure, thus appearing brilliant structural colors that serve as encoding tags for multiplexed bioassays. Besides, benefitting from the abundant specific surface area, biomarkers can be labeled on the SCSPs with high efficiency for specific detection of analytes in clinical samples. Moreover, the directional magnetic moment arrangement enables contactless magnetic manipulation of the SCSPs, and the resultant rotary motions of the SCSPs generates turbulence in the detection solution, thus significantly improving the detection efficiency and shortening the detection time. Based on these merits, a portable point‐of‐care‐testing strip integrating the rotary SCSPs is further constructed and the capability and advantages of this platform for multiplexed detection of tumor‐related exosomes in clinical samples are demonstrated. This study offers a new way for the control of bottom‐up self‐assembly and extends the configuration and application values of colloidal crystal structural colors materials.

Abstract Erythrocytes are the most abundant cells in the blood. As the results of long‐term natural selection, their specific biconcave discoid morphology and cellular composition are responsible for gaining excellent biological performance. Inspired by the intrinsic features of erythrocytes, various artificial biomaterials emerge and find broad prospects in biomedical applications such as therapeutic delivery, bioimaging, and tissue engineering. Here, a comprehensive review from the fabrication to the applications of erythrocyte‐inspired functional materials is given. After summarizing the biomaterials mimicking the biological functions of erythrocytes, the synthesis strategies of particles with erythrocyte‐inspired morphologies are presented. The emphasis is on practical biomedical applications of these bioinspired functional materials. The perspectives for the future possibilities of the advanced erythrocyte‐inspired biomaterials are also discussed. It is hoped that the summary of existing studies can inspire researchers to develop novel biomaterials; thus, accelerating the progress of these biomaterials toward clinical biomedical applications.

Objectives. Excessive inflammatory responses and reactive oxygen species (ROS) formation play pivotal roles in the pathogenesis of sepsis. Penfluroidol (PF), an oral long-acting antipsychotic drug, has been suggested to possess diverse biological properties, including antischizophrenia, antitumour effect, and anti-inflammatory activity. The purpose of this research was to explore the anti-inflammatory and antioxidative effects of penfluroidol on lipopolysaccharide (LPS)-related macrophages. Methods. The viability of RAW264.7 and THP-1 cells was measured by Enhanced Cell Counting Kit-8 (CCK-8). The production of nitric oxide was evaluated by the Nitric Oxide Assay Kit. The generation of pro-inflammatory monocytes was detected by qRT-PCR (quantitative real-time PCR) and ELISA (enzyme-linked immunosorbent assay). Oxidative stress was assessed by measuring ROS, malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The protein expression of the Nrf2/HO-1/NLRP3 inflammasome was detected by western blotting. Results. Our results indicated that no cytotoxic effect was observed when RAW264.7 and THP-1 cells were exposed to PF (0–1 μm) and/or LPS (1 μg/ml) for 24 hr. The data showed that LPS, which was repressed by PF, facilitated the generation of the pro-inflammatory molecules TNF-α and IL-6. In addition, LPS contributed to increased production of intracellular ROS compared with the control group, whereas the administration of PF effectively reduced LPS-related levels of ROS. Moreover, LPS induced the generation of MDA and suppressed the activities of SOD. However, PF treatment strongly decreased LPS-induced MDA levels and increased SOD activities in the RAW264.7 and THP-1 cells. Furthermore, our research confirmed that penfluroidol repressed the secretion of pro-inflammatory molecules by limiting the activation of the NLRP3 inflammasome and reducing oxidative effects via the Nrf2/HO-1 signaling pathway. Conclusion. Penfluroidol attenuated the imbalance of the inflammatory response by suppressing the activation of the NLRP3 inflammasome and reduced oxidative stress via the Nrf2/HO-1 signaling pathway in LPS-induced macrophages.

Abstract Responsive hydrogel microfibers can realize multiple controllable changes in shapes or properties under the stimulation of the surrounding environment, and are called as intelligent biomaterials. Recently, these responsive hydrogel microfibers have been proved to possess significant biomedical values, and remarkable progress has been achieved in biomedical engineering applications, including drug delivery, biosensors and clinical therapy, etc. In this review, the latest research progress and application prospects of responsive hydrogel microfibers in biomedical engineering are summarized. We first introduce the common preparation strategies of responsive hydrogel microfibers. Subsequently, the response characteristics and the biomedical applications of these materials are discussed. Finally, the present opportunities and challenges as well as the prospects for future development are critically analyzed.

BackgroundMicrobiome dysbiosis is considered a predictive biomarker of clinical response in renal cell carcinoma (RCC), which can be regulated by antibiotics (ATB). Multiple studies have shown that concomitant ATB administration has inhibitory effects on immunotherapy in RCC. This review aimed to assess the impact of ATB on patient survival and tumor response in RCC with immunotherapy.MethodsLiterature evaluating the effect of ATB on immunotherapy in RCC from Cochrane Library®, PubMed®, Embase®, Scopus®, and Web of Science® were systematically searched. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratio (OR) for objective response rate (ORR) and primary progressive disease (PD) were pooled as effect sizes for clinical outcomes. Subgroup analysis was conducted to reveal the determinants of the effect of ATB on immunotherapy, including time windows of ATB exposure to immunotherapy initiation, ICIs treatment and study location. The leave-one-out approach was adopted to analyze the heterogeneity formulated. Cumulative meta-analysis adding by time was used to observe dynamic changes of the results.ResultsTen studies were included in the systematic review and six studies (with n=1,104 patients) were included in the meta-analysis, four studies were excluded for overlapping patients with subsequent larger studies and lack of unique patient-level data. ATB administration was significantly correlated with shorter PFS (HR=2.10, 95%CI [1.54; 2.85], I2 = 2% after omitting study Derosa et al, 2021 detected by leave-one-out approach), shorter OS (HR=1.69, 95%CI [1.34; 2.12], I2 = 25%) and worse ORR (OR=0.58, 95%CI [0.41; 0.84]), but no difference was observed in risk of PD (OR=1.18, 95%CI [0.97; 1.44]). No significant differences existed among the subgroups for determining the determinants of ATB inhibition.ConclusionsConcomitant ATB with immunotherapy was associated with worse PFS, OS and ORR in RCC. No publication bias was observed in this study.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=349577, identifier CRD42022349577.

BackgroundThe macrophages are involved in all stages of cardiovascular diseases, demonstrating the correlation between inflammation, atherosclerosis, and myocardial infarction (MI). Here, we aim to investigate macrophages-related genes in the deterioration of atherosclerosis.MethodsGSE41571 was downloaded and the abundance of immune cells was estimated by utilizing the xCell. By utilizing the limma test and correlation analysis, differentially expressed macrophages-related genes (DEMRGs) were documented. The functional pathways and the protein–protein interaction (PPI) network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the expressions of hub DEMRGs were analyzed using the GSE135055 and GSE116250 datasets as well as atherosclerosis and MI mice model.ResultsA total of 509 differentially expressed genes (DEGs) were correlated with the abundance of macrophages and were identified as DEMRGs (Pearson correlation coefficients (PCC) > 0.6), which were mainly enriched in extracellular structure organization, lysosomal membrane, MHC protein complex binding, and so on. After screening out, 28 hub DEMRGs were obtained with degrees ≥20, including GNAI1 (degree = 113), MRPS2 (degree = 56), HCK (degree = 45), SOCS3 (degree = 40), NET1 (degree = 28), and so on. After validating using Gene Expression Omnibus (GEO) datasets and the atherosclerosis and MI mice model, eight proteins were validated using ApoE-/- and C57 mice. The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.ConclusionThe screened hub DEMRGs, SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, EIF4EBP1, and PPP4C, may be therapeutic targets for treatment and prediction in the patients with plaque progression and MI recurrent events. The kit of the eight hub DEMRGs may test plaque progression and MI recurrent events and help in the diagnosis and treatment of MI-induced heart failure (HF), thus decreasing mortality and morbidity.

When organs, especially external organs are injured, pathogens and excessive water loss can threaten the wound healing process and cause local irreversible tissue damage. Here, novel natural κ-Carrageenan microparticles (MPs) able to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration were developed using microfluidic electrospray. The side chains of κ-Carrageenan were modified with methacrylate pendant groups to make the monomer photonic cross-linkable. By changing the concentration of methacrylated-κ-Carrageenan, different porosities of MPs with controllable drug loading were achieved. The size of the MPs can also be tailored by adjusting the voltage of the applied electric field. Vascular endothelial growth factor (VEGF) and antimicrobial peptides Eumenitin were co-loaded into the microparticles (VEGF-Eumenitin-MPs) and released sustainedly in phosphate-buffered saline. The VEGF-Eumenitin-MPs had high biocompatibility and intensive antibacterial activities for bacteria. Furthermore, the antibacterial and angiogenetic properties of the VEGF-Eumenitin-MPs were demonstrated in a infectious wound model and the chronic wound healing process was significantly enhanced in vivo. Therefore, the developed porous MPs with sustained drug release properties have the potential to serve as a platform to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration.

Abstract 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.