Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis

Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas

The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA.

HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China

Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.Conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17^(+) γδ T cells

Spinal cord injury(SCI)causes motor,sensory,and autonomic dysfunctions.The gut microbiome has an important role in SCI,while short-chain fatty acids(SCFAs)are one of the main bioactive mediators of microbiota.In the present study,we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI.Allen’s method was utilized to establish an SCI model in Sprague-Dawley(SD)rats.The animals received water containing a mixture of 150 mmol/L SCFAs after SCI.After 21 d of treatment,the Basso,Beattie,and Bresnahan(BBB)score increased,the regularity index improved,and the base of support(BOS)value declined.Spinal cord tissue inflammatory infiltration was alleviated,the spinal cord necrosis cavity was reduced,and the numbers of motor neurons and Nissl bodies were elevated.Enzyme-linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(qPCR),and immunohistochemistry assay revealed that the expression of interleukin(IL)-10 increased and that of IL-17 decreased in the spinal cord.SCFAs promoted gut homeostasis,induced intestinal T cells to shift toward an anti-inflammatory phenotype,and promoted regulatory T(Treg)cells to secrete IL-10,affecting Treg cells and IL-17^(+)γδT cells in the spinal cord.Furthermore,we observed that Treg cells migrated from the gut to the spinal cord region after SCI.The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17^(+)γδT cells in the spinal cord,which inhibits the inflammatory response and promotes the motor function in SCI rats.Our findings suggest that there is a relationship among gut,spinal cord,and immune cells,and the“gut-spinal cord-immune”axis may be one of the mechanisms regulating neural repair after SCI.

Coordination-driven self-assembly of metallo-nanodrugs for local inflammation alleviation

Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable challenge.In this study,we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug delivery.The resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability,allowing for the combination of magnetic resonance imaging and anti-inflammatory therapy.In the case of osteoarthritis(OA),the metallo-nanodrugs remarkably alleviate synovial inflammation,preventing cartilage destruction and extracellular matrix loss.In addition,it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse model.This work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.

Nanoparticle-mediated corneal neovascularization treatments: Toward new generation of drug delivery systems

Corneal neovascularization(CNV) is one of the major factors for vision impairment and blindness worldwide. The current treatment for CNV focuses primarily on topical eyedrops of glucocorticoids,non-steroidal anti-inflammatory drugs, electro-coagulation and laser photo-coagulation. Unfortunately,coagulation-based treatment is restricted by corneal hemorrhage and iris atrophy. And drug treatments have limited therapeutic effects and a short duration of action. Nanoparticle-based drug delivery systems are widely applied due to their improved pharmacokinetics, optimized drug targeting and enhanced biocompatibility. In this article, we provide a comprehensive and systematic overview of the CNV nanodrug system, highlighting some of the recent advances in nanodrug design, preparation, and functional modification. Moreover, we discuss the challenges in the clinical translation and potential risks in CNV treatment. A greater effort is needed for the potential applications of nanotechnology in the field of ophthalmology.

mNGS-based dynamic pathogen monitoring for accurate diagnosis and treatment of severe pneumonia caused by fungal infections

Metagenomic next-generation sequencing(mNGs)has been widely applied to identify pathogens associated with infectious diseases.However,limited studies have explored the use of mNGs-based dynamic pathogen monitoring in intensive care unit patients with severe pneumonia.Here,we present a clinical case of an 86-year-old male patient with severe pneumonia caused by a fungal infection.During the clinical treatment,four mNGS analyses were performed within two consecutive weeks.Various respiratory fungal pathogens,including Candida orthopsilosis,Candida albicans,and Aspergillus fumigatus were detected by mNGS of bronchoalveolar lavage fluid(BALF).Based on conventional pathogen identification and clinical symptoms,the patient was diagnosed with severe pneumonia caused by a fungal infection.The abundance of fungal species decreased gradually in response to antifungal and empirical therapies,and the fungal infections were effectively con-trolled.In summary,our results demonstrated that mNGS could effectively identify pathogens in patients with severe pneumonia.Additionally,dynamic pathogen monitoring based on mNGS could assist in the precise diag-nosis of complex infections and may facilitate rapid induction of the most appropriate therapy.

Corrigendum to“Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone”[Bioact.Mater.10C(April 2022)32-47]

The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),National Key Research and Development Plan(2018YFC1105103).

Myocardial protection by heparin-based coacervate of FGF10

Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.

Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.

Causal Effect of Genetically Determined Blood Copper Concentrations on Multiple Diseases: A Mendelian Randomization and Phenome-Wide Association Study

Exposures to copper have become a health concern.We aim to explore the broad clinical effects of blood copper concentrations.A total of 376,346 Caucasian subjects were enrolled.We performed a Mendelian randomization and phenome-wide association study(MR-PheWAS)to evaluate the causal association between copper and a wide range of outcomes in UK Biobank,and we constructed a protein-protein interaction network.We found association between blood copper concentrations and five diseases in the overall population and nine diseases in male.MR analysis implicated a causal role of blood copper in five diseases(overall population),including prostate cancer(OR=0.87,95%CI 0.77-0.98),malignant and unknown neoplasms of the brain and nervous system(OR=0.58,95%CI 0.38-0.89),and hypertension(OR=0.94,95%CI 0.90-0.98),essential hypertension(OR=0.94,95%CI 0.90-0.98)and cancer of brain and nervous system(OR=0.63,95%CI 0.41-0.98).For male,except for dysphagia being newly associated with blood copper(OR=1.39,95%CI 1.18-1.63),other MR results were consistent with the overall population.In addition,the PPI network showed possible relationship between blood copper and four outcomes,namely brain cancer,prostate cancer,hypertension,and dysphagia.Blood copper may have causal association with prostate cancer,malignant and unknown neoplasms of the brain and nervous system,hypertension,and dysphagia.Considering that copper is modifiable,exploring whether regulation of copper levels can be used to optimize health outcomes might have public health importance.

In vivo performance of a rare earth free Mg-Zn-Ca alloy manufactured using twin roll casting for potential applications in the cranial and maxillofacial fixation devices

A magnesium alloy containing essential,non-toxic,biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process(TRC).Microstructure,mechanical properties,in vivo corrosion and biocompatibility have been assessed and compared to the properties of the rare earth(RE)element containing WE43 alloy.TRC Mg-0.5 wt% Zn-0.5 wt% Ca exhibited fine grains with an average grain size ranging from 70 to 150μm.Mechanical properties of a TRC Mg-0.5Zn-0.5Ca alloy showed an ultimate tensile strength of 220 MPa and ductility of 9.3%.The TRC Mg-0.5Zn-0.5Ca alloy showed a degradation rate of 0.51±0.07 mm/y similar to that of the WE43 alloy(0.47±0.09 mm/y)in the rat model after 1 week of implantation.By week 4 the biodegradation rates of both alloys studied were lowered and stabilized with fewer gas pockets around the implant.The histological analysis shows that both WE43 and TRC Mg-0.5Zn-0.5Ca alloy triggered comparable tissue healing responses at respective times of implantation.The presence of more organized scarring tissue around the TRC Mg-0.5Zn-0.5Ca alloys suggests that the biodegradation of the RE-free alloy may be more conducive to the tissue proliferation and remodelling process.

Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration

The intricate dynamic feedback mechanisms involved in bone homeostasis provide valuable inspiration for the design of smart biomaterial scaffolds to enhance in situ bone regeneration.In this work,we assembled a biomimetic hyaluronic acid nanocomposite hydrogel(HA-BP hydrogel)by coordination bonds with bisphosphonates(BPs),which are antiosteoclastic drugs.The HA-BP hydrogel exhibited expedited release of the loaded BP in response to an acidic environment.Our in vitro studies showed that the HA-BP hydrogel inhibits mature osteoclastic differentiation of macrophage-like RAW264.7 cells via the released BP.Furthermore,the HA-BP hydrogel can support the initial differentiation of primary macrophages to preosteoclasts,which are considered essential during bone regeneration,whereas further differentiation to mature osteoclasts is effectively inhibited by the HA-BP hydrogel via the released BP.The in vivo evaluation showed that the HA-BP hydrogel can enhance the in situ regeneration of bone.Our work demonstrates a promising strategy to design biomimetic biomaterial scaffolds capable of regulating bone homeostasis to promote bone regeneration.

Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone

Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure.Hence,improving osseointegration and transplantation efficiency remains important.The alteration of bone tissue microenvironment(TME)to facilitate osseointegration has been generally recognized.However,the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging.To address this concern,an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment.The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique.The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated.In the animal test,superior osseointegration between Mg-enriched graft and host bone was found,whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation.Furthermore,the bony in-growth appeared on magnesium-enriched allograft bone was significant higher.The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells.Lastly,our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.

Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing

Anti-infection and neovascularization at the wound site are two vital factors that accelerate diabetic wound healing. However, for a wound healing dressing, the two functions need to work at different sites(inner and outer), giving big challenges for dressing design. In this study, we fabricated a novel sodium alginate/chitosan(SA/CS) Janus hydrogel dressing by the assembly of SA hydrogel loaded with silver nanoparticles(Ag NPs) and CS hydrogel impregnated with L-arginine loaded sodium alginate microspheres(Arg MSs) based on electrostatic interactions to combine the two functions. The outer SA-Ag NP hydrogel could prevent infection while avoiding the deposition of Ag NPs in the wound site, and the inner CS-Arg MS hydrogel on the wound surface could realize the sustained release of L-arginine and promote vascular regeneration. The composition, morphology and swelling/degradation of the SA-Ag NP/CS-Arg MS hydrogel were characterized systematically. L-Arginine release behavior has been tested and SA-Ag NP/CSArg MS hydrogel has been confirmed for excellent biocompatibility. Antibacterial and angiogenesis assays demonstrated the antibacterial and angiogenesis characteristics of the SA-Ag NP/CS-Arg MS hydrogel. Finally, in vivo diabetic wound healing assay demonstrated that the SA-Ag NP/CS-Arg MS hydrogel could significantly accelerate re-epithelialization, granulation tissue formation, collagen deposition and angiogenesis, thereby resulting in enhanced diabetic wound healing。

Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis

Osteoarthritis(OA)is always characterized as excessive reactive oxygen species(ROS)inside articular cavity.Mimicking natural metalloenzymes with metal ions as the active centers,stable metal organic framework(MOF)formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases.Herein,a series of novel copper-morin-based MOF(CuMHs)with different molar ratios of Cu^(2+)and MH were employed to serve as ROS scavengers for OA therapy.As a result,CuMHs exhibited enhanced dispersion in aqueous solution,improved biocompatibility,and efficient ROS-scavenging ability compared to MH.On the basis of H_(2)O_(2)-stimulated chondrocytes,intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu_(6)MH(Cu^(2+)and MH molar ratio of 6:1).Meanwhile,Cu_(6)MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6,MMP13,and MMP3,and up-regulating cartilage specific gene expression as well.Importantly,Cu_(6)MH could repair mitochondrial function by increasing mitochondrial membrane potential,reducing the accumulation of calcium ions,as well as promoting ATP content production.In OA joint model,intra-articular(IA)injected Cu_(6)MH suppressed the progression of OA.It endowed that Cu_(6)MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

Preoperative virtual reduction method for pelvic fractures based on statistical shape models and partial surface data

Virtual reduction is crucial for successful and accurate reduction of pelvic fractures.Various methods have been proposed in this regard.However,not all of them are applicable to every pelvic fracture.Among these methods,the efficiency and accuracy of the method based on statistical shape models in clinical applications require further improvement.This study proposes a virtual reduction method for pelvic fractures that uses statistical shape models and partial surface data of a broken pelvis.Simulated fracture and clinical case experiments were conducted to validate the accuracy and effectiveness of the proposed method.The simulated fracture experiments yielded an average error of 1.57±0.39 mm and a maximum error of 12.82±3.54 mm.The virtual reduction procedure takes approximately 40 s.Based on three clinical case experiments,the proposed method achieves an acceptable level of accuracy compared with manual reduction by a surgeon.The proposed method offers the advantages of shorter virtual reduction times and satisfactory reduction accuracy.In the future,it will be integrated into the preoperative planning system for pelvic fracture reduction,thereby improving patient outcomes.

Corrigendum to‘Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation’[Bioactive Materials,Volume 9(March 2022)Page 491-507]

The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).