Prognostic value of ultrasound in early arterial complications post liver transplant

Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].

Applications and prospects of cryo-EM in drug discovery

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time-and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy(cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence(AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of mediumresolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

Deep learning enhanced NIR-Ⅱ volumetric imaging of whole mice vasculature

Fluorescence imaging through the second near-infrared window(NIR-Ⅱ,1000–1700 nm) allows in-depth imaging.However, current imaging systems use wide-field illumination and can only provide low-contrast 2D information, without depth resolution. Here, we systematically apply a light-sheet illumination, a time-gated detection, and a deep-learning algorithm to yield high-contrast high-resolution volumetric images. To achieve a large Fo V(field of view) and minimize the scattering effect, we generate a light sheet as thin as 100.5 μm with a Rayleigh length of 8 mm to yield an axial resolution of 220 μm. To further suppress the background, we time-gate to only detect long lifetime luminescence achieving a high contrast of up to 0.45 Icontrast. To enhance the resolution, we develop an algorithm based on profile protrusions detection and a deep neural network and distinguish vasculature from a low-contrast area of 0.07 Icontrast to resolve the 100μm small vessels. The system can rapidly scan a volume of view of 75 × 55 × 20 mm3and collect 750 images within 6mins. By adding a scattering-based modality to acquire the 3D surface profile of the mice skin, we reveal the whole volumetric vasculature network with clear depth resolution within more than 1 mm from the skin. High-contrast large-scale 3D animal imaging helps us expand a new dimension in NIR-Ⅱ imaging.

Development and Validation of a Prognostic Risk Score System for COVID-19 Inpatients:A Multi-Center Retrospective Study in China

Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.

Review of 4Pi Fluorescence Nanoscopy

Since the 1990s,continuous technical and scientific advances have defied the diffraction limit in microscopy and enabled three-dimensional(3D)super-resolution imaging.An important milestone in this pursuit is the coherent utilization of two opposing objectives(4Pi geometry)and its combination with superresolution microscopy.Herein,we review the recent progress in 4Pi nanoscopy,which provides a 3D,non-invasive,diffraction-unlimited,and isotropic resolution in transparent samples.This review includes both the targeted and stochastic switching modalities of 4Pi nanoscopy.The schematics,principles,applications,and future potential of 4Pi nanoscopy are discussed in detail.

Enhancing gene editing efficiency for cells by CRISPR/Cas9 system-loaded multilayered nanoparticles assembled via microfluidics

Most non-viral carriers for in vitro delivery of nucleic acids suffer from low efficiency of introducing m RNA and other nucleic acids,especially large m RNA.Cas9 protein is the nuclease part of the powerful gene-editing tool,CRISPR/Cas9 system,Cas9 m RNA is particularly large,thus presents a big challenge for delivery.We assembled a multilayered biodegradable nanocarrier to load Cas9 m RNA inside to protect Cas9 m RNA from degradation.We used a microfluidic chip to synthesize a small,positively charged,and degradable core to attract negatively charged Cas9 m RNA.The microfluidic assembly allows the core to be small enough to incorporate into a cationic liposome.The multilayered nanocarriers elevated the delivery efficiency of Cas9 m RNA by over 2 folds and increased the expression by over 5 folds compared to commercially used non-viral carriers.In addition,the multilayered nanocarriers do not require reduced serum medium for transfection.When using the standard complete medium for transfection,the multilayered nanocarriers could increase the expression of Cas9 m RNA by over 15 folds compared to commercially used non-viral carriers.The co-delivery of Cas9 m RNA and sg RNA via LRC elevated the gene-editing efficiency by 3 folds compared to that via commercially used non-viral carriers.Based on the higher transfection efficiency of Cas9 m RNA/sg RNA than commercially used non-viral carriers,these multilayered nanocarriers may have a good prospect as efficient commercial delivery carriers for Cas9 m RNA/sg RNA and other nucleic acids.

Investigation of artifacts by mapping SAR in thermoacoustic imaging

Microwave-induced thermoacoustic imaging(MI-TAI)remains one of the focus of attention among biomedical imaging modalities over the last decade.However,the transmission and dis-tribution of microwave inside bio-tissues are complicated,thus result in severe artifacts.In this study,to reveal the underlying mechanisms of artifacts,we deeply investigate the distribution of specific absorption rate(SAR)inside tissue-mimicking phantoms with varied morphological features using both mathematical simulations and corresponding experiments.Our simulated results,which are confirmed by the associated experimental results,show that the SAR distri-bution highly depends on the geometries of the imaging targets and the polarizing features of the microwave.In addition,we propose the potential mechanisms including Mie-scattering,Fabry-Perot-feature,small curvature effect to interpret the diffraction effect in different scenarios,which may provide basic guidance to predict and distinguish the artifacts for TAI in both fundamental and clinical studies.

Ex vivo cartilage explant model for the evaluation of chondrocyte-targeted exosomes

There is no efficient tracking system available for the therapeutic molecules delivered to cartilage.The dense matrix covering the cartilage surface is the main biological barrier that the therapeutic molecules must overcome.In this study,we aimed to establish a system that can dynamically and effectively track the therapeutic molecules delivered to cartilage.To this aim,we adopted bovine and human cartilage explants as ex vivo models for chondrocyte-targeted exosome dispersion.The efficiency of drug delivery was evaluated using frozen sections.The results of this study showed that the penetration and distribution of chondrocyte-targeted exosomes in cartilage explants can be tracked dynamically.Thus,ex vivo cartilage explants provide an effective and economic system to evaluate therapeutic drugs encapsulated in chondrocyte-targeted exosomes in preclinical studies.

Promoting interactions between cognitive science and large language models

Large language models(LLMs)have made unprecedented progress,demonstrating human-like language proficiency and an extraordinary ability to encode complex knowledge.The emergence of high-level cognitive capabilities in LLMs,such as in-context learning and complex reasoning,suggests a path toward the realization of artificial general intelligence(AGI).However,we lack scientific theories and tools to assess and interpret such an emergence of the advanced intelligence of LLMs.Artificial intelligence(AI)has been extensively applied in various areas of fundamental science to accelerate scientific research.

Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors

Overexpression of CD47 is frequently observed in various types of human malignancies,inhibiting myeloidmediated elimination of tumor cells and affecting the prognosis of cancer patients.By mapping biomarker expression,immuno-positron emission tomography has been increasingly used for patient screening and response monitoring.By immunization alpacas with recombinant human CD47,we prepared a CD47-targeting nanobody C2 and developed[^(68)Ga]Ga-NOTA-C2,followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models.By fusing C2 to an albumin binding domain(ABD),we synthesized ABDC2,which had increased in vivo half-life and improved targeting properties.We further labeled ABDC2 with^(68)Ga/^(89)Zr/177Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell-and patient-derived models.Both C2 and ABDC2 specifically reacted with human CD47 with a high KD value of 23.50 and 84.57 pM,respectively.[^(68)Ga]Ga-NOTA-C2 was developed with high radiochemical purity(99>%,n=4)and visualized CD47 expression in the tumors.In comparison to the rapid renal clearance and short half-life of[^(68)Ga]Ga-NOTA-C2,both[^(68)Ga]Ga-NOTA-ABDC2 and[^(89)Zr]Zr-DFOABDC2 showed prolonged circulation and increased tumor uptake,with the highest uptake of[^(89)Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection.Moreover,[177Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity,warranting further optimization of the treatment schedules.Taken together,we reported a series of nanobody-derived CD47-targeted agents,of which[^(68)Ga]Ga-NOTA-C2 and[^(89)Zr]Zr-DFO-ABDC2 are readily translatable.Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.

Biomedical microwave-induced thermoacoustic imaging

Microwave induced thermoacoustic imaging(MTAI)has emerged as a potential biomedical imaging modality with over 20-year growth.MTAI typically employs pulsed microwave as the pumping source,and detects the microwave-induced ultrasound wave via acoustic transducers.Therefore,it features high acoustic resolution,rich elect romagnetic contrast,and large imaging depth.Benefiting from these unique advantages,MTAI has been extensively applied to various fields including pathology,biology,material and medicine.Till now,MTAI has been deployed for a wide range of biomedical applications,including cancer diagnosis,joint evaluation,brain in-vestigation and endoscopy.This paper provides a comprehensive review on(1)essential physics(endogenous/exogenous contrast mechanisms,penetration depth and resolution),(2)hardware configurations and software implementations(excit ation source,antenna,ultrasound detector and image recovery algorithm),(3)animal studies and clinical applications,and(4)future directions.

A novel sprayable thermosensitive hydrogel coupled with zinc modified metformin promotes the healing of skin wound

A novel sprayable adhesive is established(ZnMet-PF127)by the combination of a thermosensitive hydrogel(Pluronic F127,PF127)and a coordination complex of zinc and metformin(ZnMet).Here we demonstrate that ZnMet-PF127 potently promotes the healing of traumatic skin defect and burn skin injury by promoting cell proliferation,angiogenesis,collagen formation.Furthermore,we find that ZnMet could inhibit reactive oxygen species(ROS)production through activation of autophagy,thereby protecting cell from oxidative stress induced damage and promoting healing of skin wound.ZnMet complex exerts better effects on promoting skin wound healing than ZnCl2 or metformin alone.ZnMet complex also displays excellent antibacterial activity against Staphylococcus aureus or Escherichia coli,which could reduce the incidence of skin wound infections.Collectively,we demonstrate that sprayable PF127 could be used as a new drug delivery system for treatment of skin injury.The advantages of this sprayable system are obvious:(1)It is convenient to use;(2)The hydrogel can cover irregular skin defect sites evenly in a liquid state.In combination with this system,we establish a novel sprayable adhesive(ZnMet-PF127)and demonstrate that it is a potential clinical treatment for traumatic skin defect and burn skin injury.

In situ Injectable Tetra-PEG Hydrogel Bioadhesive for Sutureless Repair of Gastrointestinal Perforation

Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal(GI)perforation management.However,several concerns remain for the existing bioadhesives including slow and/or weak adhesive,poor mechanical strength,low biocompatibility,and poor biodegradability,which largely limit their clinical application in GI perforation repair.In this work,we introduce an in situ injectable Tetra-PEG hydrogel bioadhesive(SS)composed of tetra-armed poly(ethylene glycol)amine(Tetra-PEG-NH2)and tetra-armed poly(ethylene glycol)succinimidyl succinate(Tetra-PEG-SS)for the sutureless repair of GI defects.The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid-tight sealing in the ex vivo porcine intestinal and gastric models.Importantly,the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation.The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion,suppressed inflammation,and enhanced angiogenesis.Together,our results support potential clinical applications of the SS bioadhesive for the high-efficient repair of GI perforation.

Facile Fabrication of Hyperbranched Polyacetal Quaternary Ammonium with pH-Responsive Curcumin Release for Synergistic Antibacterial Activity

In the current global crisis of antibiotic resistance,persuit of an effective multi-pathway collaborative approach to enhance antibacterial activity is urgently needed.Here,a kind of hyperbranched polyacetal quaternary ammonium(Hyper-ace-QA)with efficiently antibacterial function were synthesized by a succession of efficient click strategies.The high molecular weights can be obtained just after UV irradiation for 3 h,and the grafting ratio can be easily adjusted through controlling solvent system,molar ratio,and temperature.Cytotoxicity studies indicated that Hyper-ace-QA had good biocompatibility and can be used as a potential antibacterial dressing.More importantly,after in situ encapsulation of bioactive curcumin drugs into the hyperbranched intramolecular cavities,the acid-liable acetal linkers within the hyperbranched backbone made the loading antibacterial drugs rapidly release with pH-or bacterial-responsive behaviors since many bacteria can produce acids at the infection site by the combined actions of immune response and bacterial metabolism.Therefore,the integration of quaternary ammonium characteristics and pH-triggered curcumin release could facilitate the antibacterial activity against gram-positive Staphylococcus aureus.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be promising therapeutic alternatives for first aid treatment of wound infection in critical situations.

Electronic exoneuron based on liquid metal for the quantitative sensing of the augmented somatosensory system

The increasing demands in augmented somatosensory have promoted quantitative sensing to be an emerging need for athletic training/performance evaluation and physical rehabilitation.Neurons for the somatosensory system in the human body can capture the information of movements in time but only qualitatively.This work presents an electronic Exo-neuron(EEN)that can spread throughout the limbs for realizing augmented somatosensory by recording both muscular activity and joint motion quantitatively without site constraints or drift instability,even in strenuous activities.Simply based on low-cost liquid metal and clinically used adhesive elastomer,the EEN could be easily fabricated in large areas for limbs.It is thin(~120μm),soft,stretchable(>500%),and conformal and further shows wide applications in sports,rehabilitation,health care,and entertainment.

Energy-Dissipative and Soften Resistant Hydrogels Based on Chitosan Physical Network: From Construction to Application

In spite of biological tissue-like peculiarity,multifarious functionalities and great application prospect,the low mechanics and soften behavior of hydrogels still retain a problem to be addressed for repetitive weight-bearing fields of flexible electronics,actuators,substitutions of soft tissues,wound dressing,wearable or implantable devices.Due to the distinct combination of diversity,reversibility and impressive disruption-reconstruction capacity,the chitosan physical cross-links can server as recoverable“sacrificial bonds”to construct multifarious energy-dissipative and anti-soften hydrogels and further broaden their diversified applications.In this review,we summarized the gelation mechanisms of chitosan physical networks and highlighted the chitosan physical network based hydrogels in rational design,construction principle,and structure and performance regulation.The recent progress in functional hydrogels for flexible electronics and biomaterials was systematically discussed.Overall,the review will provide comprehensive guidelines on the design principle,performance modulation and functionality construction of energy-dissipative and soften resistant hydrogels.

An immunoassay based on lab-on-a-chip for simultaneous and sensitive detection of clenbuterol and ractopamine

Both clenbuterol(CLB)and ractopamine(RAC)areβ-adrenergic agonists.After long-term excessive intake,there will be adverse reactions such as headache,chest tightness,limb numbness,and serious lifethreatening.Simultaneous detection of CLB and RAC in related samples is of great importance for human health.In this work,we outline a microfluidics-based indirect competitive immunoassay(MICI)system that can sensitively detect residual CLB and RAC in pork,swine blood and swine urine.The rapid detection of multiple samples can be achieved in one chip,which greatly improves the detection efficiency.This method has good stability and reproducibility and the microfluidic chips are easy to manufacture.The linear ranges for CLB and RAC detection by MICI are 0.1-2.5 ng/mL and 0.1-5 ng/mL,and the limits of detection(LODs)are 0.094 ng/mL and 0.091 ng/mL,respectively.This straightforward and portable immunoassay system provides a good platform for rapid detection of harmful substances in food samples.

Light-Driven Ion Transport in Nanofluidic Devices:Photochemical,Photoelectric,and Photothermal Effects

Light-driven ion transport in nanofluidic devices is a phenomenon where ions move unidirectionally by consuming optical energy,either from low concentration to high concentration or vice versa.The light-driven unidirectional ion transport offers intriguing application potential in desalination and ion separation,osmosis energy harvesting,and ionic machines benefiting from the remote noncontact light stimulus.Here,we review recent progress in nanofluidic-based light-driven ion transport systems and emphasize similarities and differences in the three underlying working principles based on photochemical,photoelectric,and photothermal effects.The current challenges and future developments of light-driven ion transport in nanofluidic devices are discussed.We believed that this article encourages further innovation in this exciting and emerging research field.

Predicting Illness Severity and Short-Term Outcomes of COVID-19:A Retrospective Cohort Study in China

Introduction COVID-19,caused by SARS-CoV-2,is a highly contagious disease.1 By April 8,2020,more than 1,350,000 patients were diagnosed with COVID-19 globally,with more than 79,000 deaths worldwide attributable to the disease.2 Recent clinical data reported that mild and critical patients manifested different symptoms.Most of the mild patients with COVID-19 had symptoms such as fever,cough,and mild pneumonia,whereas the critical cases presented dyspnea,respiratory failure,sepsis,organ dysfunction,and even eventual death.

A Versatile Crosslinking Strategy on Facile Fabrication of Fluorescent Hydrogels via o-Phthalaldehyde Ternary Condensation

It is of great sighificance to develop rapid crosslinking strategies to enrich the functions of hydrogels and simplify the preparation process of hydrogels.Herein,we applied the ternary condensation reaction of o-phthalaldehyde(OPA)with thiol and amino moieties to con struct hydrogel n etworks with fast gelati on rate,excellent mecha nical stre ngth,and favorable stability.