Seasonal increase in nest defense,but not egg rejection,in a cuckoo host

The interactions between avian brood parasites and their hosts provide an informative and easy-to-handle system for studying coevolution.Avian brood parasitism reduces the reproductive success of hosts,and thus,hosts have evolved anti-parasitic strategies,such as rejecting parasitic eggs and adopting aggressive nest defense strategies,to avoid the cost brought on by brood parasitism.To test whether host anti-parasitic strategies are adjusted with the risk of being parasitized when the breeding seasons of brood parasites and hosts are not synchronous,we conducted a field experiment assessing nest defense and egg recognition behaviors of the Isabelline Shrike(Lanius isabellinus),a host of the Common Cuckoo(Cuculus canorus).In the local area,the host Isabelline Shrike begins to breed in April,whereas the summer migratory Common Cuckoo migrates to the local area in May and begins to lay parasitic eggs.Results showed that nest defense behaviors of the Isabelline Shrike increases significantly after cuckoo arrival,showing higher aggressiveness to cuckoo dummies,with no significant difference in attack rates among cuckoo,sparrowhawk and dove dummies,but their egg rejection did not change significantly.These results imply that Isabelline Shrikes may adjust their nest defense behavior,but not egg rejection behavior,with seasonality.

Recognition and rejection of foreign eggs of different colors in Barn Swallows

Brood parasitic birds lay eggs in the nests of other birds,and the parasitized hosts can reduce the cost of raising unrelated offspring through the recognition of parasitic eggs.Hosts can adopt vision-based cognitive mechanisms to recognize foreign eggs by comparing the colors of foreign and host eggs.However,there is currently no uniform conclusion as to whether this comparison involves the single or multiple threshold decision rules.In this study,we tested both hypotheses by adding model eggs of different colors to the nests of Barn Swallows(Hirundo rustica)of two geographical populations breeding in Hainan and Heilongjiang Provinces in China.Results showed that Barn Swallows rejected more white model eggs(moderate mimetic to their own eggs)and blue model eggs(highly non-mimetic eggs with shorter reflectance spectrum)than red model eggs(highly nonmimetic eggs with longer reflectance spectrum).There was no difference in the rejection rate of model eggs between the two populations of Barn Swallows,and clutch size was not a factor affecting egg recognition.Our results are consistent with the single rejection threshold model.This study provides strong experimental evidence that the color of model eggs can has an important effect on egg recognition in Barn Swallows,opening up new avenues to uncover the evolution of cuckoo egg mimicry and explore the cognitive mechanisms underlying the visual recognition of foreign eggs by hosts.

Disturbances rejection optimization based on improved two-degree-of-freedom LADRC for permanent magnet synchronous motor systems

Permanent magnet synchronous motor(PMSM)speed control systems with conventional linear active disturbance rejection control(CLADRC)strategy encounter issues regarding the coupling between dynamic response and disturbance suppression and have poor performance in suppressing complex nonlinear disturbances.In order to address these issues,this paper proposes an improved two-degree-of-freedom LADRC(TDOF-LADRC)strategy,which can enhance the disturbance rejection performance of the system while decoupling entirely the system's dynamic and anti-disturbance performance to boost the system robustness and simplify controller parameter tuning.PMSM models that consider total disturbances are developed to design the TDOF-LADRC speed controller accurately.Moreover,to evaluate the control performance of the TDOF-LADRC strategy,its stability is proven,and the influence of each controller parameter on the system control performance is analyzed.Based on it,a comparison is made between the disturbance observation ability and anti-disturbance performance of TDOF-LADRC and CLADRC to prove the superiority of TDOF-LADRC in rejecting disturbances.Finally,experiments are performed on a 750 W PMSM experimental platform,and the results demonstrate that the proposed TDOF-LADRC exhibits the properties of two degrees of freedom and improves the disturbance rejection performance of the PMSM system.

To analyze the differentially expressed genes in chronic rejection after renal transplantation by bioinformatics

Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of this disease, providing a theoretical basis for finding new therapeutic targets. Methods: Gene microarray data were downloaded from the Gene Expression Profiling Integrated Database (GEO) and cross-calculated to identify differentially expressed genes (DEGs). Analysis of differentially expressed genes (DEGs) with gene ontology (GO) is a method used to study the differences in gene expression under different conditions as well as their functions and interrelationships, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis is a tool used to explore the functions and pathways of genes in specific biological processes. By calculating the distribution of immune cell infiltration, the result of immune infiltration in the rejection group can be analysed as a trait in Weighted Gene Co-Expression Network Analysis (WGCNA) for genes associated with rejection. Then, protein-protein interaction networks (PPI) were constructed using the STRING database and Cytoscape software to identify hub gene markers. Results: A total of 60 integrated DEGs were obtained from 3 datasets (GSE7392, GSE181757, GSE222889). By GO and KEGG analysis, the GEDs were mainly concentrated in the regulation of immune response, defence response, regulation of immune system processes, and stimulation response. The pathways were mainly enriched in antigen processing and presentation, EBV infection, graft-versus-host, allograft rejection, and natural killer cell-mediated cytotoxicity. After further screening using WGCNA and PPI networks, HLA-A, HLA-B, HLA-F, and TYROBP were identified as hub genes (Hub genes). The data GSE21374 with clinical information was selected to construct the diagnostic efficacy and risk prediction model plots of the four hub genes, and the results concluded that all four Hub genes had good diagnostic value (area under the curve in the range of 0.794-0.819). From the inference, it can be concluded that the four genes, HLA-A, HLA-B, HLA-F and TYROBP, may have an important role in the development and progression of chronic rejection after renal transplantation. Conclusion: DEGs play an important role in the study of the pathogenesis of chronic rejection after renal transplantation, and can provide theoretical support for further research on the pathogenesis of chronic rejection after renal transplantation and the discovery of new therapeutic targets through enrichment analysis and pivotal gene screening, as well as inferential analyses of related diagnostic efficacy and disease risk prediction.

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern worldwide.Patients with comorbid conditions are at risk of adverse outcomes following COVID-19.Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection.It could lead to higher rates of inpatient complications and mortality in this patient population.However,studies on COVID-19 outcomes in liver transplant(LT)recipients have yielded inconsistent findings.AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.METHODS We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample database.Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classi-fication of Diseases,Tenth Revision coding system.The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic.Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.RESULTS A total of 15720 hospitalized LT recipients were included.Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection.In both cohorts,the median admission age was 57 years.The linear trends for LT hospitalizations did not differ significantly before and during the pandemic(P=0.84).The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020.Compared to the pre-pandemic period,a higher association was noted between LT recipients and in-hospital mortality during the pandemic,with an odds ratio(OR)of 1.69[95% confidence interval(CI):1.55-1.84),P<0.001].The frequency of transplant rejections among hospitalized LT recipients increased from 0.2%to 3.6% between January 2019 and December 2020.LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic[OR:1.53(95%CI:1.26-1.85),P<0.001].CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic.Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

Temperature Control of Proton Exchange Membrane Fuel Cell Based on Linear Active Disturbance Rejection Control

The performance of proton exchange membrane fuel cells is very sensitive to temperature. The electrochemical reaction results directly in temperature variations in the proton exchange membrane fuel cell. Ensuring effective temperature control is crucial to ensure fuel cell reliability and durability. This paper uses active disturbance rejection control in the thermal management system to maintain the operating temperature and the stack inlet and outlet temperature difference at the set value. First, key cooling system modules such as expansion tanks, coolant circulation pumps and radiators based on Simulink were built. Then, physical modeling and simulation of the fuel cell cooling system was carried out. In order to ensure the effectiveness of the control strategy and reduce the parameter tuning workload, an active disturbance rejection control parameter optimization method using an elite genetic algorithm was proposed. When the optimized control strategy responds to input disturbances, the maximum overshoot of the system is only 1.23% and can reach stability again in 30 s, so the fuel cell temperature can be controlled effectively. Simulation results show that the optimized control strategy can effectively control the stack temperature and coolant temperature difference under the influence of stepped charging current without interference or with interference, and has strong robustness and anti-interference capability.

Robust Consensus Tracking Control of Uncertain Multi-Agent Systems With Local Disturbance Rejection

In this paper,a new distributed consensus tracking protocol incorporating local disturbance rejection is devised for a multi-agent system with heterogeneous dynamic uncertainties and disturbances over a directed graph.It is of two-degree-of-freedom nature.Specifically,a robust distributed controller is designed for consensus tracking,while a local disturbance estimator is designed for each agent without requiring the input channel information of disturbances.The condition for asymptotic disturbance rejection is derived.Moreover,even when the disturbance model is not exactly known,the developed method also provides good disturbance-rejection performance.Then,a robust stabilization condition with less conservativeness is derived for the whole multi-agent system.Further,a design algorithm is given.Finally,comparisons with the conventional one-degree-of-freedombased distributed disturbance-rejection method for mismatched disturbances and the distributed extended-state observer for matched disturbances validate the developed method.

Egg rejection and egg recognition mechanism in a Chinese Azure-winged Magpie(Cyanopica cyanus)population

Recognition and rejection of foreign eggs are effective defense of hosts against brood parasitism.However,brood parasitism can impose various selection pressures on different geographic populations of the same host species.In a multiple cuckoo system in China,Azure-winged Magpies(Cyanopica cyanus)are parasitized by both Indian Cuckoos(Cuculus micropterus)and Asian Koels(Eudynamys scolopaceus).In this study,egg recognition ability and recognition mechanism of the Azure-winged Magpie were investigated using a population in Fusong,southeastern Jilin,China.The results showed that 55.6%(20/36)of the Azure-winged Magpies correctly rejected quail(Coturnix japonica)eggs in their nests,while 13.9%(5/36)of the individuals experienced rejection costs by wrongly rejecting their own eggs.Azure-winged Magpies could accurately reject the experimental eggs when the number of such eggs in the nests was the same as that of the magpie eggs.However,Azure-winged Magpies do not recognize and reject conspecific eggs(0/28).The present study indicates that the Azure-winged Magpie has moderate egg recognition ability toward non-mimetic quail eggs and shows a true recognition mechanism with rejecting foreign eggs by accurately recognizing their own eggs.However,they cannot recognize conspecific eggs.

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux

BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.

Design and analysis of active disturbance rejection control for time-delay systems using frequency-sweeping

For the typical first-order systems with time-delay,this paper explors the control capability of linear active disturbance rejection control(LADRC).Firstly,the critical time-delay of LADRC is analyzed using the frequency-sweeping method and the Routh criterion,and the stable time-delay interval starting from zero is accurately obtained,which reveals the limitations of general LADRC on large time-delay.Then in view of the large time-delay,an LADRC controller is developed and verified to be effective,along with the robustness analysis.Finally,numerical simulations show the accuracy of critical time-delay,and demonstrate the effectiveness and robustness of the proposed controller compared with other modified LADRCs.

AC-DC Fuzzy Linear Active Disturbance Rejection Control Strategy of Front Stage of Bidirectional Converter Based on V2G

Aiming at the problems of output voltage fluctuation and current total harmonic distortion(THD)in the front stage totem-pole bridgeless PFC of two-stage V2G(Vehicle to Grid)vehicle-mounted bi-directional converter,a fuzzy linear active disturbance rejection control strategy for V2G front-stage AC-DC power conversion system is proposed.Firstly,the topologicalworkingmode of the totem-pole bridgeless PFC is analyzed,and themathematical model is established.Combined with the system model and the linear active disturbance rejection theory,a double closed-loop controller is designed with the second-order linear active disturbance rejection control as the voltage outer loop and PI control as the current inner loop.The controller can realize self-adaptive tuning of the proportional gain coefficient of the active disturbance rejection controller through fuzzy reasoning and realize self-adaptive control.Simulation and experimental results show that this method can better solve the problems of slow system response and high total harmonic distortion rate of input current and effectively improve the system’s robustness.

Anti-thymocyte globulin for treatment of T-cell-mediated allograft rejection

Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Thymoglobulin(rabbit-derived,Sanofi,United States),ATG-Fresenius S(rabbit-derived),and ATGAM(equine-derived,Pfizer,United States),these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells,imparting immunosuppressive effects.Although the prevailing mechanism predominantly involves T-cell depletion via the complement-mediated pathway,alternate mechanisms have been elucidated.Optimal dosing and treatment duration of ATG have exhibited variance across randomised trials and clinical reports,rendering the establishment of standardized guidelines a challenge.The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever,chills,and skin rash in the acute phase to long-term concerns related to immunosuppression,including susceptibility to infections and malignancies.This comprehensive review aims to provide a thorough exploration of the current understanding of ATG,encompassing its mechanism of action,clinical utility in the treatment of acute renal graft rejections,specifically steroid-resistant cases,efficacy in rejection episode reversal,and a synthesis of findings from different eras of maintenance immunosuppression.Additionally,it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function.Furthermore,the review underscores the existing gaps in evidence,particularly in the context of the Banff classification of rejections,and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.

Chemokine Receptors CCR1, CCR3, CCR7 and Chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.

Statistical Analysis and Countermeasures for Specimen Rejection in the Emergency Department

The rejected specimens from the Emergency Department of the Center of Clinical Laboratory from January 1,2022 to January 1,2023 were analyzed to reduce the specimen rejection rates and to improve the quality of inspection.The results showed that there were 1488 samples of rejected specimens and the non-conforming rate was 0.58%.The departments involved were mainly the Emergency Department,the Hematology Department,the Cardiology Department,the Intensive Care Department,and the Brain Surgery Department.Among the reasons for rejection,blood hemolysis accounted for 43.15%,blood coagulation accounted for 26.61%,and the rate of insufficient specimens was 17.14%.Among them,the sample rejection rate for arterial blood gas analysis was the highest,which accounted for 1.74%;followed by specimens for coagulation test,which was 1.18%.These results indicate the main reason for producing rejected specimens is mainly due to not following the standard operating procedure.Specimen rejection can largely be avoided if the standards for specimen collection are strictly followed.

Tree‑Inspired Structurally Graded Aerogel with Synergistic Water,Salt,and Thermal Transport for High‑Salinity Solar‑Powered Evaporation

Solar-powered interfacial evaporation is an energy-efficient solution for water scarcity.It requires solar absorbers to facilitate upward water transport and limit the heat to the surface for efficient evaporation.Furthermore,downward salt ion transport is also desired to prevent salt accumulation.However,achieving simultaneously fast water uptake,downward salt transport,and heat localization is challenging due to highly coupled water,mass,and thermal transport.Here,we develop a structurally graded aerogel inspired by tree transport systems to collectively optimize water,salt,and thermal transport.The arched aerogel features root-like,fan-shaped microchannels for rapid water uptake and downward salt diffusion,and horizontally aligned pores near the surface for heat localization through maximizing solar absorption and minimizing conductive heat loss.These structural characteristics gave rise to consistent evaporation rates of 2.09 kg m^(-2) h^(-1) under one-sun illumination in a 3.5 wt%NaCl solution for 7 days without degradation.Even in a high-salinity solution of 20 wt%NaCl,the evaporation rates maintained stable at 1.94 kg m^(-2) h^(-1) for 8 h without salt crystal formation.This work offers a novel microstructural design to address the complex interplay of water,salt,and thermal transport.

Uncertainty and disturbance estimator-based model predictive control for wet flue gas desulphurization system

Wet flue gas desulphurization technology is widely used in the industrial process for its capability of efficient pollution removal.The desulphurization control system,however,is subjected to complex reaction mechanisms and severe disturbances,which make for it difficult to achieve certain practically relevant control goals including emission and economic performances as well as system robustness.To address these challenges,a new robust control scheme based on uncertainty and disturbance estimator(UDE)and model predictive control(MPC)is proposed in this paper.The UDE is used to estimate and dynamically compensate acting disturbances,whereas MPC is deployed for optimal feedback regulation of the resultant dynamics.By viewing the system nonlinearities and unknown dynamics as disturbances,the proposed control framework allows to locally treat the considered nonlinear plant as a linear one.The obtained simulation results confirm that the utilization of UDE makes the tracking error negligibly small,even in the presence of unmodeled dynamics.In the conducted comparison study,the introduced control scheme outperforms both the standard MPC and PID(proportional-integral-derivative)control strategies in terms of transient performance and robustness.Furthermore,the results reveal that a lowpass-filter time constant has a significant effect on the robustness and the convergence range of the tracking error.

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.

Fixed-Time Gradient Flows for Solving Constrained Optimization: A Unified Approach

The accelerated method in solving optimization problems has always been an absorbing topic.Based on the fixedtime(FxT)stability of nonlinear dynamical systems,we provide a unified approach for designing FxT gradient flows(FxTGFs).First,a general class of nonlinear functions in designing FxTGFs is provided.A unified method for designing first-order FxTGFs is shown under Polyak-Łjasiewicz inequality assumption,a weaker condition than strong convexity.When there exist both bounded and vanishing disturbances in the gradient flow,a specific class of nonsmooth robust FxTGFs with disturbance rejection is presented.Under the strict convexity assumption,Newton-based FxTGFs is given and further extended to solve time-varying optimization.Besides,the proposed FxTGFs are further used for solving equation-constrained optimization.Moreover,an FxT proximal gradient flow with a wide range of parameters is provided for solving nonsmooth composite optimization.To show the effectiveness of various FxTGFs,the static regret analyses for several typical FxTGFs are also provided in detail.Finally,the proposed FxTGFs are applied to solve two network problems,i.e.,the network consensus problem and solving a system linear equations,respectively,from the perspective of optimization.Particularly,by choosing component-wisely sign-preserving functions,these problems can be solved in a distributed way,which extends the existing results.The accelerated convergence and robustness of the proposed FxTGFs are validated in several numerical examples stemming from practical applications.

Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions

Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and pigs.Current knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHC II molecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHC I and II deletion.