Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Analysis and Design of a Phase Interpolator for Clock and Data Recovery

In this paper,a detailed analysis of a phase interpolator for clock recovery is presented. A mathematical model is setup for the phase interpolator and we perform a precise analysis using this model. The result shows that the output amplitude and linearity of phase interpolator is primarily related to the difference between the two input phases. A new encoding pattern is given to solve this problem. Analysis in the circuit domain was also undertaken. The simulation results show that the relation between RC time-constant and time difference of input clocks affects the linearity of the phase interpolator. To alleviate this undesired effect, two adjustable-RC buffers are added at the input of the PI. Finally,a 90nm CMOS phase interpolator,which can work in the frequency from 1GHz to 5GHz,is proposed. The power dissipation of the phase interpolator is lmW with a 1.2V power supply. Experiment results show that the phase interpolator has a monotone output phase and good linearity.

Implementing VMI service pricing strategy for 3PL corporation considering recovery costs

The collector managed inventory(CMI)management idea is introduced based on the comparison of manufacturer and third-party logistics(3PL)implementing vendor managed inventory(VMI)services.Considering recovery costs,the service pricing strategies for 3PL corporations implementing VMI are studied to meet two conditions of participation constraints and incentive-compatibility constraints.The numerical simulation results indicate that the supply chain partners' profits change after considering recovery costs,and the 3PL corporation's profits and the total profits increase first,and then decrease.The retailers' and manufacturers' profits also increase.The total profits of the supply chain have a characteristic of increasing first and then decreasing with the increase of the callback ratio of unsold products.The concrete extremum point is codetermined by price flexibility,service pricing of the 3PL corporation,callback price and callback ratio.

Flight Schedule Recovery under Uncertain Airport Capacity

Airlines adjust their flight schedules to satisfy more stringent airport capacity constraints caused by inclement weather or other unexpected disruptions.The problem will be more important and complicated if uncertain disruptions occur in hub airports.A two-stage stochastic programming model was established to deal with the realtime flight schedule recovery and passenger re-accommodation problem.The first-stage model represents the flight re-timing and re-fleeting decision in current time period when capacity information is deterministic,while the second-stage recourse model evaluates the passenger delay given the first-stage solutions when one future scenario is realized.Aiming at the large size of the problem and requirement for quick response,an algorithmic framework combining the sample average approximation and heuristic method was proposed.The computational results indicated of that the proposed method could obtain solutions with around 5% optimal gaps,and the computing time was linearly positive to the sample size.

A Parametric Study of Mesh Free Interpolation Based Recovery Techniques in Finite Element Elastic Analysis

The paper presents a parametric study on interpolation techniques based postprocessed error estimation in finite element elastic analysis by varying important parameters of recovery,interpolation scheme and type of patch construction.The quality of error estimation with recovery parameters is compared in terms of local and global effectivity of error estimation,rate of error convergence,and adaptively refined meshes.A mesh free moving least square interpolation technique with proven reliability and effectivity is introduced for improving the recovery of finite element solution errors.The post-processed finite element solutions of elastic problems are presented for performance study under different parameters of recovery technique.The study concludes that recovery parameters of interpolation method have pronounced effect on the recovery of finite element solution error and analysis in adaptive environment.

Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

A new approach for high fidelity seismic data recovery by fractal interpolation

Recovering accurate data is important for both earthquake and exploration seismology studies when data are sparsely sampled or partially missing. We present a method that allows for precise and accurate recovery of seismic data using a localized fractal recovery method. This method requires that the data are self- similar on local and global spatial scales. We present examples that show that the intrinsic structure associated with seismic data can be easily and accurately recovered by using this approach. This result, in turn, indicates that seismic data are indeed self-similar on local and global scales. This method is applicable not only for seismic studies, but also for any field studies that require accurate recovery of data from sparsely sampled datasets with partially missing data. Our ability to recover the missing data with high fidelity and accuracy will qualitatively improve the images of seismic tomography.

Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with GC.METHODS The PubMed,EMBASE,and Cochrane Library databases were used to search for eligible studies from inception to April 1,2023.The mean difference(MD),odds ratio(OR)and 95%confidence interval(95%CI)were pooled for analysis.The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores.We used Stata(V.16.0)software for data analysis.RESULTS This study consists of six studies involving 878 elderly patients.By analyzing the clinical outcomes,we found that the ERAS group had shorter postoperative hospital stays(MD=-0.51,I2=0.00%,95%CI=-0.72 to-0.30,P=0.00);earlier times to first flatus(defecation;MD=-0.30,I²=0.00%,95%CI=-0.55 to-0.06,P=0.02);less intestinal obstruction(OR=3.24,I2=0.00%,95%CI=1.07 to 9.78,P=0.04);less nausea and vomiting(OR=4.07,I2=0.00%,95%CI=1.29 to 12.84,P=0.02);and less gastric retention(OR=5.69,I2=2.46%,95%CI=2.00 to 16.20,P=0.00).Our results showed that the conventional group had a greater mortality rate than the ERAS group(OR=0.24,I2=0.00%,95%CI=0.07 to 0.84,P=0.03).However,there was no statistically significant difference in major complications between the ERAS group and the conventional group(OR=0.67,I2=0.00%,95%CI=0.38 to 1.18,P=0.16).CONCLUSION Compared to those with conventional recovery,elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

End Organ Recovery and Survival with the QuadroxD Oxygenator in Adults on Extracorporeal Membran Oxygenation

Introduction: Extracorporeal Membrane Oxygenation (ECMO) is used in selected patient with cardiogenic and/or re- spiratory shock. We report our experience with standardized management protocols and the application of the Qua- droxD oxygenator with a centrifugal pump to maximize end-organ recovery and improve survival. Methods: This is an Internal Review Board (IRB) approved, single institution retrospective study of end-organ recovery and survival in pa- tients who required ECMO for cardiogenic and/or respiratory shock between July 2010 and June 2011. Results: Sixteen patients (median age: 46 years) were initiated on either Veno-Arterial (VA) or Veno-Venous (VV) ECMO. Cardiogenic shock, acute respiratory distress syndrome (ARDS) and a combined respiratory and cardiogenic compromise were the primary indications for ECMO in 8 (50%), 5 (31%) and 3 (19%) patients respectively. The median time on ECMO was 8 days (range: 4 - 26 days). Twelve patients (75%) were successfully weaned off ECMO, of which four (25%) were bridged to a ventricular assist device (VAD) and eight (50%) were weaned to recovery. All eight patients (100%) that were weaned to recovery and two patients (50%) that were bridged to a VAD were successfully discharged from the hospital, resulting in a discharge rate of 63%. There was an improvement in pre- vs. post-ECMO AST (449 IU/L vs. 63 IU/L, p Conclusion: ECMO using the QuadroxD oxygenator and a centrifugal pump, coupled with standardized management protocols is beneficial in carefully selected patients. Improvement or main- tenance of end-organ function is associated with successful bridge to device therapy and/or increased survival.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Multidisciplinary approach toward enhanced recovery after surgery for total knee arthroplasty improves outcomes

Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of life.With an increased prevalence of obesity and greater life expectancies,total knee arthroplasty(TKA)is now one of the major arthroplasty surgeries performed for knee osteoarthritis.When enhanced recovery after surgery(ERAS)was introduced in TKA,clinical outcomes were enhanced and the economic burden on the healthcare system was reduced.ERAS is an evidence-based scientific protocol aimed at ameliorating the surgical stress response.ERAS aims to enhance the recovery phase,which encompasses multidisciplinary strategies at every step of perioperative care,including the rehabilitation phase.Implementation of ERAS in TKA aids in reducing the length of hospital stay,improving pain management,reducing perioperative complications,and enhancing patient satisfaction.Multidisciplinary collaboration,integrating the expertise of anesthesiologists,orthopedic surgeons,nursing personnel,and other healthcare professionals,is the cornerstone of ERAS in patients undergoing TKA.

Synergistic anionic/zwitterionic mixed surfactant system with high emulsification efficiency for enhanced oil recovery in low permeability reservoirs

Emulsification is one of the important mechanisms of surfactant flooding. To improve oil recovery for low permeability reservoirs, a highly efficient emulsification oil flooding system consisting of anionic surfactant sodium alkyl glucosyl hydroxypropyl sulfonate(APGSHS) and zwitterionic surfactant octadecyl betaine(BS-18) is proposed. The performance of APGSHS/BS-18 mixed surfactant system was evaluated in terms of interfacial tension, emulsification capability, emulsion size and distribution, wettability alteration, temperature-resistance and salt-resistance. The emulsification speed was used to evaluate the emulsification ability of surfactant systems, and the results show that mixed surfactant systems can completely emulsify the crude oil into emulsions droplets even under low energy conditions. Meanwhile,the system exhibits good temperature and salt resistance. Finally, the best oil recovery of 25.45% is achieved for low permeability core by the mixed surfactant system with a total concentration of 0.3 wt%while the molar ratio of APGSHS:BS-18 is 4:6. The current study indicates that the anionic/zwitterionic mixed surfactant system can improve the oil flooding efficiency and is potential candidate for application in low permeability reservoirs.

Problem identification and revitalization strategies for the recovery and reconstruction of traditional villages in the Ms 6.8 Luding Earthquake

Post-disaster reconstruction is a topic of global concern,and traditional villages have special heritage attributes and need to face more requirements and obstacles in post-disaster reconstruction.This paper summarizes four concepts based on the research on post-disaster reconstruction both domestically and internationally,as well as the recovery and reconstruction of cultural heritage.Through a field survey of traditional villages in the Ms 6.8 Luding earthquake-stricken area,it is found that there are problems such as insufficient awareness of heritage value,misalignment of scientific reconstruction technology,and insufficient protection of reconstruction elements during the reconstruction process.Traditional villages face the risk of declining or even loss of heritage value.In order to effectively protect traditional villages and inherit the carrier of regional culture,four targeted reconstruction response strategies are proposed,i.e.,to"establish special planning for traditional village preservation","emphasize recovery of the authenticity of village heritage","ensure elements for village heritage recovery"and"promote the activation and utilization of village heritage",based on the problems discovered during the survey and the four concepts summarized in the research on post-disaster reconstruction of traditional villages.The research results hope to provide useful reference for ancient cultural areas affected by earthquakes on how to protect cultural heritage during the post-disaster reconstruction process.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Roles of Corporate Reputation and Service Recovery in Food Safety Crises:A Case Study of Food Hygiene Incidents in Hot Pot Restaurants

Food hygiene incidents in hot pot restaurants were studied,and a relationship model between corporate reputation and consumers behavioral intention was established.Hot pot consumers of hot pot restaurants were surveyed through questionnaires.The results show that corporate reputation positively affects service recovery and repurchase intention,and service recovery positively influences repurchase intention,while corporate reputation affects repurchase intention through service recovery.In other words,under the situation of enterprise crises,the service recovery of an enterprise can restore its image and reputation.Therefore,when an enterprise has a crisis,it should positively respond to the crisis incident,and take timely crisis recovery to maintain its positive image.

Correlation linking illness perception,negative emotions,and the post-operative recovery effect in patients with perianal disease

BACKGROUND Improvements in the standard of living have led to increased attention to perianal disease.Although surgical treatments are effective,the outcomes of postoperative recovery(POR)are influenced by various factors,including individual differences among patients,the characteristics of the disease itself,and the psychological state of the patient.Understanding these factors can help healthcare providers develop more personalized and effective post-operative care plans for patients with perianal disease.AIM To investigate the effect of illness perception(IP)and negative emotions on POR outcomes in patients with perianal disease.METHODS A total of 146 patients with perianal disease admitted to the First People's Hospital of Changde City from March to December 2023 were recruited.We employed a general information questionnaire,the Brief Illness Perception Questionnaire(B-IPQ),and the Hospital Anxiety and Depression Scale(HADS).We used the 15-item Quality of Recovery Score(QoR-15)to measure patients’recovery effects.Finally,we conducted Pearson’s correlation analysis to examine the relationship between pre-operative IP and anxiety and depression levels with POR quality.RESULTS Fifty-three(36.3%)had poor knowledge of their disease.Thirty(20.5%)were suspected of having anxiety and 99(67.8%)exhibited symptoms.Forty(27.4%)were suspected of having depression and 102(69.9%)displayed symptoms.The B-IPQ,HADS-A,HADS-D,and QoR-15 scores were 46.82±9.97,12.99±3.60,12.58±3.36,and 96.77±9.85,respectively.There was a negative correlation between pre-operative IP,anxiety,and depression with POR quality.The influence of age and disease course on post-operative rehabilitation effect are both negative.The impact of B-IPQ,HADS-A,and HADS-D on POR was negative.Collectively,these variables accounted for 72.6%of the variance in POR.CONCLUSION The quality of POR in patients with perianal disease is medium and is related to age,disease course,IP,anxiety,and depression.

丙二酸盐克罗诺杆菌rpoS基因突变株与回补株的构建

丙二酸盐克罗诺杆菌(Cronobacter malonaticus)在面对环境胁迫时,通过自身调节机制适应压力。rpoS基因作为一种稳定期σ因子和压力应答过程中的主要调节因子,在细菌抵抗或耐受环境胁迫压力中发挥重要作用。文章运用red同源重组技术和质粒表达系统,构建C.malonaticus G362的rpoS基因缺失株ΔrpoS和回补菌株ΔrpoS-com,为研究丙二酸盐克罗诺杆菌中rpoS基因的功能提供遗传材料。生长曲线测定结果表明,rpoS基因缺失未对正常培养条件下细菌生长产生显著影响。

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.