Mesenchymal stem cells arouse myocardial NAD+ metabolism to alleviate microgravity-induced cardiac dysfunction.

After prolonged space operations, astronauts showed maladaptive atrophy within mostly left-ventricular myocardium, resulting in cardiac dysfunction. However, the mechanism of cardiac dysfunction under microgravity conditions is unclear, and the relevant prevention and treatment measures also need to be explored. Through simulating the microgravity environment with a tail suspension (TS) model, we found that long-term exposure to microgravity promotes aging of mouse hearts, which is closely related to cardiac dysfunction. The intravenous administration of adipose-derived mesenchymal stem cells (ADSCs) emerged preventive and therapeutic effect against myocardial senescence and the decline in cardiac function. Plasma metabolomics analysis suggests the loss of NAD+ in TS mice and motivated myocardial NAD + metabolism and utilization in ADSCs-treated mice, likely accounting for ADSCs' function. Oral administration of nicotinamide mononucleotide (NMN, a NAD + precursor) showed similar therapeutic effect to ADSCs treatment. Collectively, these data implicate the effect of ADSCs in microgravity-induced cardiac dysfunction and provide new therapeutic ideas for aging-related maladaptive cardiac remodeling.

Is axillary artery cannulation necessary in type II hybrid aortic arch repair for acute type A aortic dissection?

INTRODUCTION: Axillary artery cannulation (AAC) has been widely employed in total arch replacement surgeries using the frozen elephant trunk (FET) technique for acute type A aortic dissection (ATAAD), showing better clinical results than femoral artery cannulation (FAC). Nevertheless, in type II hybrid arch repair (HAR), FAC is crucial for lower body perfusion. Hence, it is unclear whether AAC remains necessary or if AAC represents a more advantageous method for initiating cardiopulmonary bypass. METHODS: We conducted a study involving patients diagnosed with ATAAD who underwent type II HAR from August 2021 to December 2022. Demographic baseline and intraoperative data were collected, and the postoperative outcomes of patients receiving FAC only were compared with those receiving AAC. RESULTS: There were no significant differences in baseline demographics between patients who underwent FAC alone (n = 46) and those who underwent AAC (n = 39). Patients who underwent AAC showed a lower incidence of transient neurological dysfunction (TND) post-surgery compared to those who underwent FAC (12.8% vs 32.6%, p = .032). There were no significant differences between the groups in terms of postoperative mortality within 30 days, permanent neurological dysfunction (PND), length of stay in the intensive care unit (ICU) and postoperative ward, duration of mechanical ventilation, and other complications. CONCLUSIONS: Axillary artery cannulation may decrease the incidence of postoperative transient neurological dysfunction (TND) in type II HAR for ATAAD. Nonetheless, studies with larger sample sizes are necessary.

Research on Fiber-Optic Optical Coherence Ranging System Based on Laser Frequency Scanning Interferometry.

In this paper, a system for absolute distance measurement is proposed based on laser frequency scanning interferometry (FSI). The system utilizes a digitally tunable laser as the light source and employs synchronized pulses to drive an analog-to-digital converter (ADC) for interference signal acquisition. The frequency domain demodulation for absolute distance measurement is achieved through a three-spectrum line interpolation method based on the Hanning window. The system takes advantage of the spatial filtering characteristics of a single-mode optical fiber and the diffuse reflection properties of light to achieve a high integration of the prism system that forms the interference optical path. The resulting integrated fiber-optic probe is capable of measuring the distance to a non-cooperative target even when oriented at a certain angle with the target. We designed and fabricated a portable prototype. Experimental validation demonstrated that the maximum measurement distance of the system is 73.51 mm with a standard deviation of less than 0.19 µm for optimal measurement results. Even when there is an offset angle, the system maintains good measurement repeatability.

Research on the Algorithm of Position Correction for High-Speed Moving Express Packages Based on Traditional Vision and AI Vision.

The rapid development of the logistics industry poses significant challenges to the sorting work within this sector. The fast and precise identification of moving express parcels holds immense significance for the performance of logistics sorting systems. This paper proposes a motion express parcel positioning algorithm that combines traditional vision and AI-based vision. In the traditional vision aspect, we employ a brightness-based traditional visual parcel detection algorithm. In the AI vision aspect, we introduce a Convolutional Block Attention Module (CBAM) and Focal-EIoU to enhance YOLOv5, improving the model's recall rate and robustness. Additionally, we adopt an Optimal Transport Assignment (OTA) label assignment strategy to provide a training dataset based on global optimality for the model training phase. Our experimental results demonstrate that our modified AI model surpasses traditional algorithms in both parcel recognition accuracy and inference speed. The combined approach of traditional vision and AI vision in the motion express parcel positioning algorithm proves applicable for practical logistics sorting systems.

Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments.

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats' SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.

Urban energy performance improvement policy selection in China based on policy effect prediction: An analysis from the dimensions of economy, environment and well-being.

The environmental pollution and social well-being issue caused by the huge energy consumption in cities reflect the urgency of improving urban energy performance from multiple dimensions of economy, environment, and well-being. As a result, various countries and cities have promulgated a series of policies. However, the complexity of the policies makes the categories and utilities need to be further clarified, and the diseconomy caused by the lag of policy effect evaluation makes the focus of policy implementation need to be clear in advance. Therefore, based on public choice theory, this research follows the idea of "prior analysis" and takes Chinese cities as the research object. Firstly, the collected energy performance improvement policies of Chinese cities were analyzed and classified by the content analysis method, and the main utilities of all policies and the specific utilities of each category were summarized. Based on the multiple dimensions of urban energy performance research (namely, economy, environment and well-being dimensions), this research summarized the policy utilities that help to improve the urban energy performance of each dimension, and also preset the policy utility values. Secondly, the effect prediction model for urban energy performance improvement policies in each dimension was constructed by Back-propagation (BP) neural network. Thirdly, the energy performance of Chinese cities in 2020 measured by Data Envelopment Analysis method was taken as the benchmark value, and the energy performance of Chinese cities in 2025 measured by the policy effect prediction model was taken as the comparison value. According to the results of performance improvement, the energy performance improvement policies of Chinese cities were selected respectively from the dimensions of economy, environment and well-being. This research shows that: the energy performance improvement policies of Chinese cities mainly include six categories, namely energy conservation and emission reduction policies, energy development policies, ecological environmental policies, fiscal and tax policies, industrial policies and economic and social policies. It is needed to focus on ecological environmental policies, fiscal and tax policies and industrial policies to improve urban energy performance from the economic dimension. For the environmental dimension, the key and priority policies are ecological environmental policies. Compared with the economic dimension, the focus of implementing policies adds economic and social policies in the well-being dimension. In the implementation of policies, the differences of energy performance among cities can be reduced through multi-feature analysis of cities or regions, appropriate adjustment of specific measures and targets, and improvement of digital information management of urban energy performance. This research can effectively help cities clarify which policies require higher implementation intensity and attention before and during policy implementation, thereby maximizing multi-dimensional urban energy performance.

Effects of pretransplant peritoneal vs hemodialysis modality on outcome of first kidney transplantation from donors after cardiac death.

BACKGROUND: The effect of pretransplant peritoneal dialysis (PD) or hemodialysis (HD) modality on outcomes of kidney transplantation (KT) for end-stage renal disease (ESRD) is debatable. We evaluated the outcomes these modalities in KT from donor after cardiac death (DCD). METHODS: A cohort of 251 patients on HD, PD or pre-emptive who underwent first KT from DCD between January 2014 and December 2016 were prospectively analyzed to compare for outcomes on recovery of renal function, complications as well as patient and graft survival. The patients were followed till August 2017. Data on 104 HD and 98 PD were available for final comparative outcome analysis, 5 pre-emptive were analyzed as the control group. RESULTS: Both HD and PD group patients were well matched for demographic and baseline characteristics. The follow-up period was 12.5 (3.0, 22.0) months in HD and 12.0 (6.0, 20.0) months in PD patients. Post-transplant renal functions between the two groups showed no differences. Among PD patients, 16 (16.3%) suffered delayed graft function, versus 19 (18.3%) in HD, with no statistical differences (p = 0.715). Complications of acute rejection, infections were comparable between the groups. The patient survival, graft survival and death-censored graft survival were similar for HD and PD after adjusting for other multiple risk factors. CONCLUSIONS: Our results indicate that outcome of first KT from DCD is not affected by pretransplant dialysis modality of PD or HD in aspects of recovery of renal function, complications as well as patient and graft survival.

Luminescence determination of microRNAs based on the use of terbium(III) sensitized with an enzyme-activated guanine-rich nucleotide.

A method is reported for the fluorometric quantitation of microRNA. It is making use of a luminescent probe deribed from terbium(III) ion whose fluorescence is sensitized with a guanine-rich (G-rich) nucleotide. The probe has a large Stokes' shift and strong and sharp emission bands. The assay relies on the wide substrate specificity of terminal deoxynucleotidyl transferase (TdTase), which catalyzes the formation of long G-rich nucleotides when using microRNA primer as a trigger to start the polymerization. The addition of Tb(III) induces the formation of a G-quadruplex from the G-rich nucleotide, and this strongly enhances the green fluorescence of Tb(III) (peaking at 545 nm upon photoexcitation at 290 nm). Specifically, microRNA-21 was chosen as the analyte. The fluorescence intensity of Tb(III) increases linearly in the 1 pM to 1 nM microRNA concentration range, and the detection limit is as low as 0.11 pM. The method can distinguish between family members of microRNA and performs excellently even when applied to extracts of cancer cells. Graphical abstract A fluorometric technique is reported for the determination of microRNA. It is based on signal enhancement based on the sensitization of terbium(III) via a guanine-rich nucleotide sequence. Klenow Fragment exo- (KFexo-) generates DNA sequence at the 3'-OH of microRNA, and terminal deoxynucleotidyl transferase (TdTase) catalyzes the formation of long G-rich nucleotides.

Post-Translational Modification of Adiponectin Affects Lipid Accumulation, Proliferation and Migration of Vascular Smooth Muscle Cells.

BACKGROUND/AIMS: Adiponectin (Apn) is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. Previous reports showed that several conserved lysine residues within the N-terminal collagenous domain of Apn are modified by hydroxylation and glycosylation. Here, we investigated the potential roles of post-translational modifications of Apn on the function of human vascular smooth muscle cells (VSMCs). METHODS: Blood samples of 92 coronary artery disease (CAD) patients and 20 healthy volunteers were collected and total and high molecular weight (HMW) Apn concentration and glycosylation were analyzed. RESULTS: The results revealed that total and HMW Apn derived from blood samples of CAD patients with severe stenosis significantly increased, however the glycosylation of HMW Apn significantly decreased. Functional studies of human VSMCs revealed that glycosylated Apn significantly inhibited the oxidized LDL-induced lipid accumulation, proliferation and migration of VSMCs, whereas non-glycosylated Apn had no inhibitory effects. CONCLUSION: Taken together, these data suggest that glycosylation of Apn is critically involved in regulating function against atherosclerosis by inhibiting lipid accumulation and proliferation and migration of VSMCs.

Long-term kidney survival analyses in IgA nephropathy patients under steroids therapy: a case control study.

BACKGROUND: Corticosteroids are preferred to treat patients with active IgA nephropathy (IgAN), and beneficial effects from the short-term use of corticosteroids have been confirmed. However, a large number of patients will progress to end-stage renal disease after a long time follow-up. This study aimed to evaluate kidney disease progression and risk factors on kidney survival in IgAN patients receiving steroids treatment. METHODS: Two hundred biopsy-proven IgAN patients who received corticosteroid therapy were enrolled and followed for a median period of 63.33 months. Risk factors on kidney survival were retrospectively investigated by the Cox proportional hazards model. RESULTS: Of the two hundred patients, twenty patients showed progression of renal impairment at the end of follow-up. The median and interquartile range values for initial serum creatinine were 89.2 and 68.08-121.35 µmol/L, respectively. Multivariate Cox regression analyses revealed that relapse, non-remission, time-averaged eGFR (TA-eGFR), and time-averaged serum albumin (TA-ALB) were independently associated with the kidney progression. Those with TA-ALB levels <35 g/L and TA-eGFR levels <60 mL/min/1.73 m(2) were less likely to recover from kidney progression. Patients were more likely to show kidney function deterioration, when they had non-remission or relapse after corticosteroids treatment. CONCLUSION: This study demonstrated that relapse, non-remission, TA-eGFR, and TA-ALB could serve as independent predictors of long term prognosis of IgAN patients receiving corticosteroid therapy.

Time-averaged albumin predicts the long-term prognosis of IgA nephropathy patients who achieved remission.

BACKGROUND: Primary IgA nephropathy (IgAN) is the most common form of idiopathic glomerulonephritis worldwide. Although most patients are able to achieve remission with the current therapy, a large number of patients will still progress to end-stage renal disease. This study aimed to evaluate kidney disease progression and the risk factors for progression in IgAN patients who achieved remission. METHODS: Patients from a prospective database with IgAN were included in this study. All the subjects had achieved a complete remission (CR) or partial remission (PR) following 6 months of therapy. Renal survival and the relationship between the clinical parameters and composite renal outcomes were assessed. RESULTS: The study comprised 878 IgAN patients recruited between January 2005 and December 2010. Overall, 632 patients were enrolled in this study. The data from the 369 patients who achieved remission were analyzed; the mean follow-up time was 49 months. The median serum creatinine (SCr) concentration at baseline was 91.3 µmol/L, and the time-averaged creatinine (TA-SCr) was 91.8 µmol/L. The mean serum albumin (ALB) level at baseline was 39.4 g/L, and the time-averaged serum albumin (TA-ALB) was 42.1 g/L. Multivariate Cox regression analyses revealed that the TA-ALB and TA-SCr levels were independently associated with the composite renal outcome. The patients with a TA-SCr value > 120 µmol/L and a TA-ALB level < 38 g/L were less likely to recover from renal progression. CONCLUSION: The strong predictive relationship of low TA-ALB and high TA-SCr levels with progression observed in this study suggests that TA-ALB may serve as a marker of the long-term renal prognosis of IgAN patients who have achieved remission.

Lightweight bobbin yarn detection model for auto-coner with yarn bank.

The automated replacement of empty tubes in the yarn bank is a critical step in the process of automatic winding machines with yarn banks, as the real-time detection of depleted yarn on spools and accurate positioning of empty tubes directly impact the production efficiency of winding machines. Addressing the shortcomings of traditional methods, such as poor adaptability and low sensitivity in optical and visual tube detection, and aiming to reduce the computational and detection time costs introduced by neural networks, this paper proposes a lightweight yarn spool detection model based on YOLOv8. The model utilizes Darknet-53 as the backbone network, and due to the dense spatial distribution of yarn spool targets, it incorporates large selective kernel units to enhance the recognition and positioning of dense targets. To address the issue of excessive focus on local features by convolutional neural networks, a bi-level routing attention mechanism is introduced to capture long-distance dependencies dynamically. Furthermore, to balance accuracy and detection speed, a FasterNeck is constructed as the neck network, replacing the original convolutional blocks with Ghost convolutions and integrating with FasterNet. This design minimizes the sacrifice of detection accuracy while achieving a significant improvement in inference speed. Lastly, the model employs weighted IoU with a dynamic focusing mechanism as the bounding box loss function. Experimental results on a custom yarn spool dataset demonstrate a notable improvement over the baseline model, with a high-confidence mAP of 94.2% and a compact weight size of only 4.9 MB. The detection speed reaches 223FPS, meeting the requirements for industrial deployment and real-time detection.

Research on high-speed classification and location algorithm for logistics parcels based on a monocular camera.

The rapid development of the logistics industry has driven innovations in parcel sorting technology, among which the swift and precise positioning and classification of parcels have become key to enhancing the performance of logistics systems. This study aims to address the limitations of traditional light curtain positioning methods in logistics sorting workshops amidst high-speed upgrades. This paper proposes a high-speed classification and location algorithm for logistics parcels utilizing a monocular camera. The algorithm combines traditional visual processing methods with an enhanced version of the lightweight YOLOv5 object detection algorithm, achieving high-speed, high-precision parcel positioning. Through the adjustment of the network structure and the incorporation of new feature extraction modules and ECIOU loss functions, the model's robustness and detection accuracy have been significantly improved. Experimental results demonstrate that this model exhibits outstanding performance on a customized logistics parcel dataset, notably enhancing the model's parameter efficiency and computational speed, thereby offering an effective solution for industrial applications in high-speed logistics supply.

Efficacy of a novel percutaneous pedicle screw fixation and vertebral reconstruction versus the traditional open pedicle screw fixation in the treatment of single-level thoracolumbar fracture without neurologic deficit.

Objective: The aim of this study was to compare the efficacy and safety of a novel percutaneous pedicle screw fixation and vertebral reconstruction (PPSR) vs. that of open pedicle screw fixation (OPSF) in the treatment of thoracolumbar fractures. Methods: This retrospective study enrolled 153 patients who underwent PPSR and 176 patients who received OPSF. Periprocedural characteristics, radiographic parameters, and clinical outcomes were compared between the two groups. Results: The operation duration was 93.843 ± 20.611 in PPSR group and 109.432 ± 11.903 in OPSF group; blood loss was 131.118 ± 23.673 in PPSR group and 442.163 ± 149.701 in OPSF group, incision length was 7.280 ± 1.289 in PPSR group and 14.527 ± 2.893 in OPSF group, postoperative stay was 8.732 ± 1.864 in PPSR group and 15.102 ± 2.117 in OPSF group, and total hospitalization costs were 59027.196 ± 8687.447 in PPSR group and 73144.432 ± 11747.567 in OPSF group. These results indicated that these parameters were significantly lower in PPSR compared with those in OPSF group. No significant difference was observed in the incidence of complications between the two groups. The radiographic parameters including height of the anterior vertebra, Cobb angle, and vertebral wedge angle were better in PPSR group than in OPSF group. Recovery rate of AVH was 0.449 ± 0.079 in PPSR group and 0.279 ± 0.088 in OPSF group. Analysis of clinical results revealed that during postoperative period, the VAS and ODI scores in PPSR group were lower than those in OPSF group. Conclusions: Collectively, these results indicated that PPSR more effectively restored the height of anterior vertebra and alleviated local kyphosis compared with OPSF. Moreover, the VAS and ODI scores in PPSR group were better than those of OPSF group.

C4d as a Screening Tool and an Independent Predictor of Clinical Outcomes in Lupus Nephritis and IgA Nephropathy.

BACKGROUND: As an indispensable marker of complement cascades activation, C4d was confirmed of its crucial role in the pathogenesis of both lupus nephritis (LN) and IgA nephropathy (IgAN). While the studies directly comparing the diagnostic value, and outcomes predicting function of C4d between LN and IgAN are still absent. METHODS: A cohort of 120 LN patients, 120 IgAN patients who were diagnosed by renal biopsy between January 2015 and December 2017 and 24 healthy age matched controls were prospectively analyzed. The patients were followed till December 2020. The outcomes were adverse disease treatment response (disease relapse) and kidney disease progression event (decline of estimated glomerular filtration rate by more than 20% or end-stage kidney disease). The renal C4d deposition proportion and pattern were compared between IgAN and LN patients. In addition, the relationship between renal C4d deposition and disease subtypes, disease relapse as well as disease progression for LN and IgAN patients were also analyzed. RESULTS: The LN, IgAN patients and healthy controls were well matched in ages. The follow-up period was 38.5 (30.3-60.8) months for LN patients and 45.0 (30.5-57.0) months for IgAN patients. 78 patients (65.0%) with LN had renal C4d deposition, compared with only 39 IgAN patients (32.5%) with C4d deposition in renal tissues (P < 0.001). The LN patients shared different renal C4d distribution patterns with IgAN patients. Compared with IgAN patients, the C4d deposition in LN patients was significantly more in renal glomerulus (P < 0.001) and less in renal tubules (P = 0.003). For disease subtypes, renal C4d deposition was especially strong in class V membranous LN and IgAN with tubulointerstitial fibrosis (T1/T2) lesions. Renal C4d deposition was independently correlated with the disease relapse of LN patients (HR = 1.007, P = 0.040), and acted as an independent predictor of disease progression during the follow-up period for IgAN patients (HR = 1.821, P = 0.040). CONCLUSIONS: Renal C4d distribution proportion and pattern differed between LN and IgAN patients. The presence of C4d in renal tissue acted as an independent predictor of relapse for LN patients and disease progression for IgAN patients.

Identification of a novel 14-3-3zeta binding site within the cytoplasmic domain of platelet glycoprotein Ibalpha that plays a key role in regulating the von Willebrand factor binding function of glycoprotein Ib-IX.

RATIONALE: The interaction between platelet glycoprotein (GP) Ib-IX and von Willebrand factor (VWF) is initiated by conformational changes in immobilized VWF and is also regulated by the intraplatelet proteins 14-3-3zeta and filamin A. Both 14-3-3zeta and filamin A associate with the cytoplasmic domain of GPIbalpha, whereas little is known about their relationship in regulating the VWF binding function of GPIb-IX. OBJECTIVE: To explore the mechanism underlying the roles of 14-3-3zeta and filamin A in regulating the VWF binding function of GPIb-IX. METHODS AND RESULTS: A truncation mutant of GPIbalpha (Delta565) deleting the C-terminal 14-3-3zeta binding sites retained 14-3-3zeta binding function, in contrast, deletion of the C-terminal residues 551 to 610 of GPIbalpha totally abolished 14-3-3zeta binding, indicating that the residues 551 to 564 of GPIbalpha are important in the interaction between 14-3-3zeta and GPIb-IX. An antibody recognizing phosphorylated R557GpSLP561 sequence reacted with GPIbalpha suggesting phosphorylation of a population of GPIbalpha molecules at Ser559, and a membrane permeable phosphopeptide (MP-P), R557GpSLP561 corresponding to residues 557 to 561 of GPIbalpha eliminated the association of 14-3-3zeta with Delta565. MP-P also promoted GPIb-IX association with the membrane skeleton, and inhibited ristocetin-induced platelet agglutination, VWF binding to platelets and platelet adhesion to immobilized VWF. Furthermore, a GPIb-IX mutant replacing Ser559 of GPIbalpha with alanine showed an enhanced association with the membrane skeleton, reduced ristocetin-induced VWF binding, and diminished ability to mediate cell adhesion to VWF under flow conditions. CONCLUSIONS: These data suggest a phosphorylation-dependent binding of 14-3-3zeta to central filamin A binding site of GPIbalpha, and the dimeric 14-3-3zeta binding to both the C-terminal site and central RGpSLP site inhibits GPIb-IX association with the membrane skeleton and promotes the VWF binding function of GPIb-IX.

The predictive value of urinary kidney injury molecular-1 for long-term graft function in kidney transplant patients: a prospective study.

BACKGROUND: Monitoring allograft function during the early stages is crucial, and therefore requires biomarkers more sensitive than serum creatinine (Scr). Kidney injury molecular-1 (KIM-1) is a potent biomarker; however, disparities exist in the literature concerning its predictive value in allograft function. Therefore, this study aimed to evaluate its predictive value for the long-term prognosis of kidney transplantation patients. METHODS: A prospective study with a cohort comprising 160 patients scheduled for kidney transplantation was conducted to evaluate the predictive power of urinary KIM-1 (uKIM-1) and other renal ischemia-reperfusion biomarkers including urinary L-type fatty acid binding protein (uL-FABP), urinary N-acetyl-ß-D glucosaminidase (uNAG), and urinary neutrophil gelatinase-related lipoprotein (uNGAL) for allograft prognosis. RESULTS: One hundred and forty kidney recipients who were admitted to our hospital between September 2014 and December 2017 with a median follow-up of 30.3 months were included. Thirty-seven recipients had functional delayed graft function (fDGF) in the first week post transplantation, and 42 recipients had progressed to allograft dysfunction [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] by the end of the study, while nine recipients deteriorated into allograft loss (defined by the initiation of dialysis). The levels of uKIM-1 in the fDGF group were higher than those in the immediate graft function (IGF) recipients (P<0.05) at 0 hour post transplantation [5.885 (4.420-7.913) vs. 4.605 (3.417-5.653) ng/mmol], and on the first day post transplantation [5.569 (4.181-6.722) vs. 4.002 (3.222-6.488) ng/mmol]. The levels of uL-FABP in the fDGF group were also higher than those in the IGF group at 0 hour post transplantation (89.818±39.332 vs. 69.187±37.926 µg/mmol) and on the third day post transplantation [77.835 (60.368-100.678) vs. 66.841 (28.815-89.783) µg/mmol]. Multivariate Cox regression analysis demonstrated that recipients with higher uKIM-1 levels on the first day post transplantation had a 23.5% increase in the risk of developing fDGF and a 27.3% increase in the risk of prolonged renal allograft dysfunction. CONCLUSIONS: uKIM-1 on the first day post transplantation can predict short-term graft function and is a potent biomarker for the long-term prognosis of graft function.

Improving Prognostic and Chronicity Evaluation of Chronic Kidney Disease with Contrast-Enhanced Ultrasound Index-Derived Peak Intensity.

The capability of contrast-enhanced ultrasound (CEUS) to assess the prognosis and chronicity of chronic kidney disease (CKD) was evaluated in patients diagnosed with CKD in 2014 at Ren Ji Hospital, Shanghai, China. Time-intensity curves and quantitative indexes were created using QLab quantification software. Kidney biopsies were analyzed with α-smooth muscle actin immunohistochemistry. According to the renal chronicity score, patients were divided into four groups: minimal (n = 14), mild (n = 73), moderate (n = 49) and severe (n = 31). Multivariate logistic regression analysis revealed that the derived peak intensity (DPI) was independently associated with the renal chronicity score. Of 167 CKD patients (median follow-up: 30.4 ± 18.7 mo), 31 (18.6%) exhibited CKD progression, with a decline in the glomerular filtration rate of more than 25% or end-stage renal disease. Multivariate Cox regression analysis revealed that a lower DPI was independently associated with CKD progression. This study indicates that DPI is a reliable CEUS parameter for evaluating chronic renal changes and an independent prognostic factor of CKD.

Physiological Acclimatization of the Liver to 180-Day Isolation and the Mars Solar Day.

Physiological changes in humans are evident under environmental conditions similar to those on a Mars mission involving both a space factor (long-term isolation) and a time factor (the Mars solar day). However, very few studies have investigated the response of the liver to those conditions. Serum protein levels, bilirubin levels, aminotransferase activities, blood alkaline phosphatase, gamma-glutamyltransferase, lipid levels, and serum cytokines interleukin-6 and interferon-γ levels were analyzed 30 days before the mock mission; on days 2, 30, 60, 75, 90, 105, 120, 150, and 175 of the mission; and 30 days after the mission, in four subjects in 4-person 180-day Controlled Ecological Life Support System Experiment. Serum protein levels (total protein and globulin) decreased and bilirubin increased under the isolation environment from day 2 and exhibited chronic acclimatization from days 30 to 175. Effects of the Mars solar day were evident on day 75. Blood lipid levels were somewhat affected. No obvious peak in any enzyme level was detected during the mission. The change tendency of these results indicated that future studies should explore whether protein parameters especially globulin could serve as indicators of immunological function exposure to the stress of a Mars mission.

Shear-induced interaction of platelets with von Willebrand factor results in glycoprotein Ibalpha shedding.

Shear-induced platelet adhesion through the interaction of glycoprotein (GP) Ibalpha with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture is a prerequisite for the physiological hemostatic process or pathological thrombus formation in stenosed arteries. Here we show that shear-induced interaction of platelets with immobilized VWF results in GPIbalpha ectodomain shedding. Washed platelets were exposed to VWF-coated glass capillary or cone-and-plate viscometer at different shear rates, and GPIbalpha ectodomain was shed from platelets, while a small mass of GPIbalpha COOH-terminal peptide, approximately 17 kDa, was increased correspondingly. The extent of GPIbalpha shedding was enhanced with the concentration of immobilized VWF and the time duration of constant shear stress, whereas it was obviously reduced with the decreased number of adherent platelets. Pretreatment of platelets with membrane-permeable calpain inhibitors and metalloproteinase inhibitor abolished shear-induced GPIbalpha shedding. Furthermore, GPIbalpha shedding was obviously diminished by anti-integrin-alphaIIbbeta3 monoclonal antibody SZ21, phosphatidylinositol 3-kinase inhibitor wortmannin, and cell-permeable calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. These results indicate that shear-induced platelet-VWF interaction results in calpain and metalloproteinase-dependent GPIbalpha ectodomain shedding. These findings not only have a physiological implication in understanding the presence of glycocalicin in normal circulation, but also suggest a novel mechanism for the negative regulation of platelet function and the limitation of platelet thrombus infinite formation under pathophysiological flow conditions.