Comparative study of the clinical efficacy of all-inside and traditional techniques in anterior cruciate ligament reconstruction

BACKGROUND Many studies have focused on the femoral tunnel technique and fixation method,but few studies have involved the tibial tunnel technique and fixation method.The all-inside technique is one of the new techniques that has been described in recent years.All-inside anterior cruciate ligament(ACL)reconstruction is based on a tibial socket instead of a full tunnel.This method has many potential advantages.AIM To compare clinical outcomes of knee ACL autograft reconstruction using allinside quadrupled semitendinosus(AIST)and traditional hamstring tendon(TBT)techniques.METHODS From January 2017 to October 2019,the clinical data of 80 patients with ACL reconstruction were retrospectively analyzed,including 67 males and 13 females.The patients had an average age of 24.3±3.1 years(age range:18-33 years).The AIST technique was used in 42 patients and the TBT technique was used in 38 patients.The time between operation and injury,operative duration,postoperative visual analogue scale(VAS)score and knee functional recovery were recorded and compared between the two groups.The International Knee Documentation Committee(IKDC)and Lysholm scoring system were used to comprehensively evaluate clinical efficacy.RESULTS Eighty patients were followed for 24-36 mo,with an average follow-up duration of 27.5±1.8 mo.There were no significant differences in the time between surgery and injury,operative duration,IKDC and Lysholm scores of the affected knee at the last follow-up evaluation between the two groups.There were significant differences in VAS scores 1 d,3 d,7 d,2 wk and 1 mo after surgery(P<0.05).There was no significant difference in VAS score at 3 mo,6 mo and 1 year after operation.CONCLUSION The efficacy of the AIST ACL reconstruction technique was comparable to the TBT technique,but the postoperative pain was less with the AIST technique.Thus,the AIST technique is an ideal treatment choice for ACL reconstruction.

SGK3 overexpression correlates with a poor prognosis in endoscopically resected superficial esophageal squamous cell neoplasia:A long-term study

BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection.METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled.Immunohistochemistry was used to evaluate SGK3 expression.RESULTS SGK3 was overexpressed in 55(59.8%)patients with ESCN.SGK3 overexpression showed a significant correlation with death(P=0.031).Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group(P=0.013 and P=0.004,respectively).Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients(hazard ratio 4.729;95% confidence interval:1.042-21.458).CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival.Thus,it might be a new prognostic factor for ESCN.

Mechanism of adipose-derived mesenchymal stem cell exosomes in the treatment of heart failure

BACKGROUND Heart failure(HF)is a global health problem characterized by impaired heart function.Cardiac remodeling and cell death contribute to the development of HF.Although treatments such as digoxin and angiotensin receptor blocker drugs have been used,their effectiveness in reducing mortality is uncertain.Researchers are exploring the use of adipose-derived mesenchymal stem cell(ADMSC)exosomes(Exos)as a potential therapy for HF.These vesicles,secreted by cells,may aid in tissue repair and regulation of inflammation and immune responses.However,further investigation is needed to understand the specific role of these vesicles in HF treatment.AIM To investigate the mechanism of extracellular vesicles produced by ADMSC s in the treatment of HF.METHODS Exogenous surface markers of ADMSCs were found,and ADMSCs were cultured.RESULTS The identification of surface markers showed that the surface markers CD44 and CD29 of adipose-derived stem cells(ADSCs)were well expressed,while the surface markers CD45 and CD34 of ADSCs were negative,so the cultured cells were considered ADSCs.Western blotting detected the Exo surface marker protein,which expressed CD63 protein but did not express calnexin protein,indicating that ADSC-derived Exos were successfully extracted.CONCLUSION The secretion of MSCs from adipose tissue can increase ATP levels,block cardiomyocyte apoptosis,and enhance the heart function of animals susceptible to HF.The inhibition of Bax,caspase-3 and p53 protein expression may be related to this process.

Chinese Expert Consensus on Early Prevention and Intervention of Sepsis

Sepsis is currently a major problem and challenge facing the medical community.With rapid development and progress of modern medicine,researchers have put more and more attention on sepsis;meanwhile,the morbidity and mortality of sepsis remains high despite great efforts from experts in various fields.According to updated guidelines,sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.Infection is the initial step of sepsis progression,and development from infection to sepsis is a complex pathophysiological process,including pathogen invasion,cytokine release,capillary leakage,microcirculation dysfunction,etc.which finally leads to organ metabolic disorders and functional failure.According to the latest recommended international guidelines of Sepsis 3.0,the presence of infection and SOFA score≥2 are considered as the diagnostic criteria for sepsis,and the"rescue"measures mainly focus on reversal of organ dysfunction.However,despite nearly two decades of efforts,the"Save Sepsis Campaign"has not achieved satisfactory results.Emergency medicine is the frontier subject of acute and severe illness which treats patients with acute infections at the earliest.If at this stage,physicians can predict the possibility of sepsis progression from demographic characteristics,localize the pathogen and infection,detect the inflammatory storms by tests of cytokines and evaluate the severity of the infection with more effective clinical scoring system,and then take effective measures to prevent infection from developing into sepsis in high-risk patients,the morbidity and mortality of sepsis in patients with acute infection will be greatly reduced.Based on this situation,Chinese emergency medicine experts proposed the concept of"preventing and blocking"sepsis,and launched the nationwide"Preventing Sepsis Campaign in China(PSCC)"nationwide.The main concept is summarized as"three early and two reduces"which includes early detection,early diagnosis and early intervention during the"pre-symptomatic"and"peri-septic"stage in order to reduce the incidence of sepsis and it proposed a new approach for diagnosis and treatment of acute severe infection.This consensus is jointly advocated,discussed and written by four academic associations in the field of emergency medicine and five scholarly publishing organizations.More than 40 experts from fields of emergency medicine,critical care medicine,infectious diseases,pharmacy and laboratory medicine have participated in several rounds of deliberation and finally reached consensus on the criteria of identifying patients with acute infection,taking anti-infective treatments,screening of high-risk patients with sepsis,detection and treatment of inflammatory storm,protection of vascular endothelial cells and the regulation of coagulation function,as well as strategies of liquid support and organ function protection etc.The consensus summarizes the commonly used clinical diagnosis criteria and treatment measures of sepsis both in Western medicine and traditional Chinese medicine for clinicians in order to provide evidence for the diagnosis and treatment of the disease.

Early patellar tendon rupture after total knee arthroplasty: A direct repair method

BACKGROUND Patellar tendon rupture after total knee arthroplasty(TKA)is a catastrophic complication.Although the occurrence of this injury is rare,it can lead to significant dysfunction for the patient and is very tricky to deal with.There has been no standard treatment for early patella tendon rupture after TKA,and long-term follow-up data are lacking.AIM To introduce a direct repair method for early patella tendon rupture following TKA and determine the clinical outcomes and complications of this method.METHODS During the period of 2008 to 2021,3265 consecutive TKAs were retrospectively reviewed.Twelve patients developed early patellar tendon rupture postoperatively and were treated by a direct repair method.Mean follow-up was 5.7 years.Demographic,operative,and clinical data were collected.The clinical outcomes were assessed using the Western Ontario and McMaster Universities(WOMAC)score,the Hospital for Special Surgery(HSS)score,knee range of motion,extensor lag,and surgical complications.Descriptive statistics and paired t test were employed to analyze the data.RESULTS For all 12 patients who underwent direct repair for early patellar tendon rupture,3 patients failed:One(8.3%)for infection and two(17.6%)for re-fracture.The two patients with re-fracture both underwent reoperation to reconstruct the extensor mechanism and the patient with infection underwent revision surgery.The range of motion was 109.2°±10.6°preoperatively to 87.9°±11°postoperatively,mean extensor lag was 21°at follow-up,and mean WOMAC and HSS scores were 65.8±30.9 and 60.3±21.7 points,respectively.CONCLUSION This direct repair method of early patellar tendon rupture is not an ideal therapy.It is actually ineffective for the recovery of knee joint function in patients,and is still associated with severe knee extension lag and high complication rates.Compared with the outcomes of other repair methods mentioned in the literature,this direct repair method shows poor clinical outcomes.

Expert consensus guidelines on clinical use of Xiyanping injection for acute infectious diseases

Xiyanping injection,a traditional Chinese medicine injection made of andrographolide sulfonate,consisting of well-defined ingredients with antiviral,antibacterial,anti-inflammatory and antipyretic efficacy,has been widely used for treating infectious diseases of respiratory and digestive systems.However,its wide applications may easily lead to unreasonable clinical medication.In order to guide the precise clinical application and rational use of Xiyanping injection,experts in related fields conducted systematically literature review,evaluated and deliberated the application of Xiyanping injection in treating acute infectious diseases using evidence-based medicine method,and jointly drafted the consensus to summarize types of acute infectious diseases in children and adults that can be treated with Xiyanping injection,and recommend the intervention time,usage and dosage,course of treatment and combined medication of the injection.Besides,the consensus elucidates the safety,precautions and contraindications of the injection,so as to provide guidance for clinical use.

Inhibition of aberrant Hif1αactivation delays intervertebral disc degeneration in adult mice

The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease(DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate(EP) and annulus fibrosus(AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol(2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn-1Mg porous scaffolds as biodegradable bone implants

Zinc(Zn)alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions,having a great application potential for repairing bone defect.In this work,a hydroxyapatite(HA)/polydopamine(PDA)composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion,and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin.The microstructure,degradation behavior,biocompatibility,antibacterial performance and osteogenic activities were systematically investigated.Compared with as-built Zn-1Mg scaffolds,the rapid increase of Zn2+,which resulted to the deteriorated cell viability and osteogenic differentiation,was inhibited due to the physical barrier of the composite coating.In vitro cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance.Significantly improved osteogenic and antibacterial functions were also observed according to in vivo implantation in the lateral femoral condyle of rats.The design,influence and mechanism of the composite coating were discussed accordingly.It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells

Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.

Mechanisms of hyponatremia and diabetes insipidus after acute spinal cord injury:a critical review

The incidence of hyponatremia after spinal cord injury was reported to be between 25 and 80%.Hyponatremia can lead to a variety of clinical symptoms,from mild to severe and even life-threatening.Hyponatremia is often associated with diabetes insipidus,which refers to insufficient arginine vasopressin(AVP)secretion or defective renal response to AVP,with clinical manifestations of syndromes such as hypoosmolality,polydipsia,and polydipsia.Recent mechanistic studies on hyponatremia and diabetes insipidus after acute spinal cord injury have been performed in isolation,without integrating the above two symptoms into different pathological manifestations that occur in the same injury state and without considering the acute spinal cord injury patient’s condition as a whole.The therapeutic principles of CSWS and SIADH are in opposition to one another.It is not easy to identify the mechanism of hyponatremia in clinical practice,which makes selecting the treatment difficult.According to the existing theories,treatments for hyponatremia and diabetes insipidus together are contraindicated,whether the mechanism of hyponatremia is thought to be CSWS or SIADH.In this paper,we review the mechanism of these two pathological manifestations and suggest that our current understanding of the mechanisms of hyponatremia and diabetes insipidus after high acute cervical SCI is insufficient,and it is likely that there are other undetected pathogenetic mechanisms.

Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events,including pathogen clearance,immunological modulation,and osteogenesis.In this study,we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial,immunomodulatory,and osteogenic effects using electrospinning technology.This scaffold’s piezoelectric signal output under ultrasound(US)control can be similar to the physiological electrical signals of healthy bone tissue,creating a truly biomimetic electrical microenvironment in the bone defect.In vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation,migration,and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ultrasound.Furthermore,the scaffold exhibits inhibitory effects on the growth of E.coli and S.aureus,as well as the ability to induce M2 macrophage polarization,indicating potent antibacterial and immunomodulatory properties.In vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats,effectively inhibit bacterial colonization,and reduce inflammatory responses.Altogether,this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing,thus providing a simple and effective solution for bone defects.

Surface demineralized freeze-dried bone allograft followed by reimplantation in a failed mandibular dental implant

The removal of a failed implant with high torque causes significant damage to the surrounding tissue,compromising bone regeneration and subsequent osseointegration in the defect area.Here,we report a case of carrier screw fracture followed by immediate implant removal,bone grafting and delayed reimplantation.A dental implant with a fractured central carrier screw was removed using the bur-forceps technique.The resulting three-wall bone defect was filled with granular surface demineralized freeze-dried bone allograft(SD-FDBA).Cone-beam computerized tomography was performed at 1week,6months and 15months postoperatively and standardized for quantitative evaluation.The alveolar bone width and height at 15months post-surgery were about 91%of the original values,with a slightly lower bone density,calculated using the gray value ratio.The graft site was reopened and was found to be completely healed with dense and vascularized bone along with some residual bone graft.Reimplantation followed by restoration was performed 8months later.The quality of regenerated bone following SD-FDBA grafting was adequate for osseointegration and longterm implant success.The excellent osteogenic properties of SD-FDBA are attributed to its human origin,cortical bone-like structure,partly demineralized surfaces and bone morphogenetic protein-2-containing nature.Further investigation with more cases and longer follow-up was required to confirm the final clinical effect.

Gas Leakage Detection and Pressure Difference Identification by Asymmetric Differential Pressure Method

Currently,the measurement methods for pneumatic system leakage include bubbling,ultrasonic,and pressure detection methods.These methods are sensitive to high-precision sensors,long detection times,and stable external environments.The traditional differential pressure method involves severe differential pressure fluctuations caused by environmental pressure fluctuations or electromagnetic noise interference of sensors,leading to inaccurate detection.In this paper,a differential pressure fitting method for an asymmetric differential pressure cylinder is proposed.It overcomes the limitation of the detection efficiency caused by the asynchronous temperature recovery of the two chambers in the asymmetric differential pressure method and uses the differential pressure substitution equation to replace the differential calculation of the differential pressure.The improved differential pressure method proposes an innovation based on the detection principle and calculation method.Additionally,the influence of the parameters in the differential pressure substitution equation on the leakage calculation results was simulated,and the specific physical significance of the parameters of the differential pressure substitution equation was explained.The experiments verified the fitting effect and proved the accuracy of this method.Compared with the traditional differential pressure method,the maximum leakage deviation of inhibition was 0.5 L/min.Therefore,this method can be used to detect leaks in air tanks.

Application of dynamic recrystallization model in AZ12 magnesium alloy rolling process

To deeply understand the dynamic recrystallization behavior of as-cast AZ12 magnesium alloy in deformation process,the uniaxial hot compression experiments were implemented through systematic isothermal compression experiments.The true strain of thermal compression experiments was set to 50%with temperatures of 200,250,300,350,400℃and the strain rates of 0.001,0.01,0.1,1 s^(-1).The Dynamic Recrystallization(DRX)kinetic model of AZ12 magnesium alloy was established and the accuracy of this model was verified.The model is used to predict the volume fraction of the sheet obtained by rolling through different rolling passes under the condition of consistent total reduction(50%).And the predicted results are in good agreement with the experimental results.

Highly fluorescence Ta_(4)C_(3) MXene quantum dots as fluorescent nanoprobe for heavy ion detection and stress monitoring of fluorescent hydrogels

Compared with other transition metal Mxene derived quantum dots(MQD_(S)),Ta-based Mxene quantum dots have good functionality,but Ta-based Mxene quantum dots and their applications have not been studied so far.In this paper,we report for the first time the synthesis of high fluorescence quantum yield(QY) N-doped Ta_(4)C_(3) quantum dots(N-MQDs) using Ta_(4)C_(3) quantum dots in acid reflux damaged Ta_(4)C_(3) nanosheets as precursors and ethylenediamine as nitrogen source.The prepared N-MQDs have excellent blue photoluminescence(PL) properties,particle size is only 2.60 nm,QY is up to 23.4%,and good stability.In addition,it has been reported that N-MQDs can be used as fluorescent probe for detection of Fe;and remote force sensing analysis In liquid ion sensing,N-MQDS shows a unique selective quenching of Fe;with a detection limit as low as 2 μmol/L,and has great potential as a fast and super-sensitive fluorescent probe for the detection of heavy ion.More importantly,in solid mechanics sensing,the introduction of N-MQDs into self-healing hydrogels can be developed into a fluorescent hydrogel that can be used for accurate remote force measurement and applied in the field of mechanical sensing analysis.Therefore,Ta-based N-MQDs show excellent potential in the field of fluorescence sensing,which provides a door for multi-dimensional sensing of new materials in the future.

The clinical effectiveness and safety of using epidermal growth factor,fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing:a systematic review and meta-analysis

Background:Promoting wound healing is crucial to restore the vital barrier function of injured skin.Growth factor products including epidermal growth factor(EGF),fibroblast growth factor(FGF)and granulocyte-macrophage colony stimulating factor(GM-CSF)have been used for decades although no systematic evaluation exists regarding their effectiveness and safety issues in treating acute skin wounds.This has resulted in a lack of guidelines and standards for proper application regimes.Therefore,this systematic review and meta-analysis was performed to critically evaluate the effectiveness and safety of these growth factors on skin acute wounds and provide guidelines for application regimes.Methods:We searched PubMed/Medline(1980-2020),Cochrane Library(1980-2020),Cochrane CENTRAL(from establishment to 2020),ClinicalTrials.gov(from establishment to 2020),Chinese Journal Full-text Database(CNKI,1994-2020),China Biology Medicine disc(CBM,1978-2019),Chinese Scientific Journal Database(VIP,1989-2020)andWanfang Database(WFDATA,1980-2019).Randomized controlled trials(RCTs),quasi-RCTs and controlled clinical trials treating patients with acute skin wounds from various causes and with those available growth factors were included.Results:A total of 7573 papers were identified through database searching;229 papers including 281 studies were kept after final screening.Administering growth factors significantly short-ened the healing time of acute skin wounds,including superficial burn injuries[mean differ-ence(MD)=−3.02;95%confidence interval(CI):−3.31∼−2.74;p<0.00001],deep burn injuries(MD=−5.63;95%CI:−7.10∼−4.17;p<0.00001),traumata and surgical wounds(MD=−4.50;95%CI:−5.55∼−3.44;p<0.00001).Growth factors increased the healing rate of acute skin wounds and decreased scar scores.The incidence of adverse reactions was lower in the growth factor treatment group than in the non-growth factor group.Conclusions:The studied growth factors not only are effective and safe for managing acute skin wounds,but also accelerate their healing with no severe adverse reactions.

Proteomics provides individualized options of precision medicine for patients with gastric cancer

While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.

A structure-supporting,self-healing,and high permeating hydrogel bioink for establishment of diverse homogeneous tissue-like constructs

The ready-to-use,structure-supporting hydrogel bioink can shorten the time for ink preparation,ensure cell dispersion,and maintain the preset shape/microstructure without additional assistance during printing.Meanwhile,ink with high permeability might facilitate uniform cell growth in biological constructs,which is beneficial to homogeneous tissue repair.Unfortunately,current bioinks are hard to meet these requirements simultaneously in a simple way.Here,based on the fast dynamic crosslinking of aldehyde hyaluronic acid(AHA)/N-carboxymethyl chitosan(CMC)and the slow stable crosslinking of gelatin(GEL)/4-arm poly(ethylene glycol)succinimidyl glutarate(PEG-SG),we present a time-sharing structure-supporting(TSHSP)hydrogel bioink with high permeability,containing 1%AHA,0.75%CMC,1%GEL and 0.5%PEG-SG.The TSHSP hydrogel can facilitate printing with proper viscoelastic property and self-healing behavior.By crosslinking with 4%PEG-SG for only 3 min,the integrity of the cell-laden construct can last for 21 days due to the stable internal and external GEL/PEG-SG networks,and cells manifested long-term viability and spreading morphology.Nerve-like,muscle-like,and cartilage-like in vitro constructs exhibited homogeneous cell growth and remarkable biological specificities.This work provides not only a convenient and practical bioink for tissue engineering,targeted cell therapy,but also a new direction for hydrogel bioink development.

Formulation of pH-responsive PEGylated nanoparticles with high drug loading capacity and programmable drug release for enhanced antibacterial activity

In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges like poor biocompatibility,premature drug release,suboptimal targeting to infection sites and short blood circulation time are still challenging.To achieve targeted drug delivery and enhance antibacterial activity,here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin(PEG-Schiff-Van)prodrug and free Van in one drug delivery system.The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition.Notably,on account of the combination of physical encapsulation and chemical conjugation of vancomycin,these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior,which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period.In addition,more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity.Using this strategy,this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites,thereby presenting prominent antibacterial therapy both in vitro and in vivo.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be a promising class of antimicrobial materials for potential clinical translation.

The ubiquitin ligase E6AP facilitates HDAC6-mediated deacetylation and degradation of tumor suppressors

Dear Editor,Protein acetylation status can regulate protein stability via the ubiquitin-proteasome pathway,which plays a critical role in the regulation of various cellular functions and becomes a target for cancer therapy.1,2 Histone deacetylase 6(HDAC6)belongs to the class II of the histone deacetylase/acuc/apha family and regulates cancer cell proliferation,invasion,and metastasis.3 Combination of HDAC6 inhibitors(HDAC6i)with proteasome inhibitors(PI)shows synergistic anticancer activity.4 Although many studies reveal how acetyltransferases/deacetylases regulate protein acetylation and subsequent protein ubiquitination and degradation,whether an E3 ubiquitin ligase regulates protein acetylation remains largely unknown.In addition,the mechanisms undelying synergistic anticancer activity of HDAC6i and PI remain poorly understood.