Science Progress最新文献

Peripheral nerve and large-scale muscle injuries result in significant disability, necessitating the development of biomaterials that can restore functional deficits by promoting tissue regrowth in an electroactive environment. Among these materials, graphene is favored for its high conductivity, but its low bioactivity requires enhancement through biomimetic components. In this study, we extrusion printed graphene-poly(lactide-co-glycolide) (graphene) lattice scaffolds, aiming to increase bioactivity by incorporating decellularized extracellular matrix (dECM) derived from mouse pup skeletal muscle. We first evaluated these scaffolds using human-induced pluripotent stem cell (hiPSC)-derived motor neurons co-cultured with supportive glia, observing significant improvements in axon outgrowth. Next, we tested the scaffolds with C2C12 mouse and human primary myoblasts, finding no significant differences in myotube formation between dECM-graphene and graphene scaffolds. Finally, using a more complex hiPSC-derived 3D motor neuron spheroid model co-cultured with human myoblasts, we demonstrated that dECM-graphene scaffolds significantly improved axonal expansion towards peripheral myoblasts and increased axonal network density compared to graphene-only scaffolds. Features of early neuromuscular junction formation were identified near neuromuscular interfaces in both scaffold types. These findings suggest that dECM-graphene scaffolds are promising candidates for enhancing neuromuscular regeneration, offering robust support for the growth and development of diverse neuromuscular tissues.

One of the best ways to improve new learning and increase memory strength is by reprocessing the recently acquired information, for example, by thinking of it again. Synaptic plasticity, the process by which neurons change the strength of their connections with each other, is fundamental for learning and memory formation. Yet, at present, it is unclear how reprocessing information drives synaptic plasticity to support memory improvement. A new study suggests that reprocessing enhances memory formation by recruiting more synapses to represent the new memory, thus increasing its strength.

Objective: The objective of this study was to investigate the correlation between metformin exposure and the incidence of lactic acidosis in critically ill patients.

Methods: The patients with type 2 diabetes mellitus (T2DM) were included from Medical Information Mart for Intensive Care IV database (MIMIC-IV). The primary outcome was the incidence of lactic acidosis. The secondary outcomes were lactate level and in-hospital mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. The multivariate logistic regression was used to explore the correlation between metformin exposure and the incidence of lactic acidosis. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion.

Results: We included 4939 patients. There were 2070 patients in the metformin group, and 2869 patients in the nonmetformin group. The frequency of lactic acidosis was 5.7% (118/2070) in the metformin group and it was 4.3% (122/2869) in the nonmetformin group. There was a statistically significant difference between the two groups (P < 0.05). The lactate level in the metformin group was higher than in the nonmetformin group (2.78 ± 2.23 vs. 2.45 ± 2.24, P < 0.001). After PSM, the frequency of lactic acidosis (6.3% vs. 3.7%, P < 0.001) and lactate level (2.85 ± 2.38 vs. 2.40 ± 2.14, P < 0.001) were significantly higher in the metformin group compared with the nonmetformin group. In multivariate logistic models, the frequency of lactic acidosis was obviously increased in metformin group, and the adjusted odds ratio (OR) of metformin exposure was 1.852 (95% confidence interval (CI) = 1.298-2.643, P < 0.001). The results were consistent with subgroup analysis except for respiratory failure subgroup. Metformin exposure increased lactate level but did not affect the frequency of lactic acidosis in patients of respiratory failure with hypercapnia. However, the in-hospital mortality between metformin and nonmetformin group had no obvious difference (P = 0.215). In sensitivity analysis, metformin exposure showed similar effect as the original cohort.

Conclusions: In critically ill patients with T2DM, metformin exposure elevated the incidence of lactic acidosis except for patients of respiratory failure with hypercapnia, but did not affect the in-hospital mortality.

Insights into mechanisms driving either activation or inhibition of immune response are crucial in understanding the pathology of various diseases. The differentiation of viral from endogenous RNA in the cytoplasm by pattern-recognition receptors, such as retinoic acid-inducible gene I (RIG-I), is one of the essential paths for timely activation of an antiviral immune response through induction of type I interferons (IFN). In this mini-review, we describe the most recent developments centered around RIG-I's structure and mechanism of action. We summarize the paradigm-changing work over the past few years that helped us better understand RIG-I's monomeric and oligomerization states and their role in conveying immune response. We also discuss potential applications of the modulation of the RIG-I pathway in preventing autoimmune diseases or induction of immunity against viral infections. Overall, our review aims to summarize innovative research published in the past few years to help clarify questions that have long persisted around RIG-I.

Introduction: Persistent withdrawal occlusion (PWO) is a specific catheter malfunction characterized by the inability to withdraw blood through the device. The most common cause of PWO in ports is the presence of a fibroblastic sleeve (FS). If malfunction occurs, medication can be applied incorrectly with the increased risk of complications.

Methods: One hundred seventy-seven cases of PWO in venous ports were managed. We focused on evaluating the cause of PWO, the frequency of occurrence of FS, and the options to address the malfunction. The patients underwent fluoroscopy with a contrast agent administration. Mechanical disruption (MD) with a syringe of saline using the flush method was used; in case of its failure, subsequent administration of a lock solution with taurolidine and urokinase, or low-dose thrombolysis with alteplase was indicated. Demographic data were compared with a control group.

Results: A significantly higher proportion of female patients was found in the cohort of patients with PWO (80.3% vs 66.3%, p = 0.004), dominantly patients with ovarian cancer (12.8% vs 4.8%, p = 0.022). No effect of the cannulated vein or the type of treatment on the incidence of PWO was demonstrated. The presence of FS was verified in 70% of cases. MD with a syringe was successful in 53.5% of cases. A significantly shorter time to referral (3 weeks) was demonstrated with successful management. The overall success rate of achieving desobliteration by MD alone or in combination with a thrombolytic (urokinase or alteplase) administration was 97.4%.

Conclusion: We created a method for resolving PWO using MD +/- application of thrombolytics with 97.4% success rate. Current evidence showed that FS is not likely to be affected by thrombolytic drugs; however, we have ascertained an effect of these drugs, proposing a hypothesis of microthrombotic events at the tip of the catheter if fibroblastic sleeve is present.

This study aims to explore: (1) the validity of post-exercise ultra-short-term heart rate variability (HRV_ust) after two different bouts of repeated sprint ability test (RSA), and (2) the relationship between HRV_ust measure and RSA performance. Twenty adolescent male futsal players voluntarily participated in this study (age: 17.65 ± 1.81 years, body height: 170.88 ± 4.98 cm, body weight: 61.78 ± 4.67 kg). The participants performed a standard RSA test (RSA_standard) and an RSA test with a 10% decrement of the best sprint time test (RSA_10%decrement) on two separate occasions within a week. On both occasions, a 5-min resting electrocardiography was administered pre- and post-RSA exercise protocols. The first 30-s (HRV_ust30s), 60-s (HRV_ust60s), and 60-120-s (HRV_ust1-2min) were extracted and used to compare with the standard of 5-min HRV recording (HRV_criterion). The natural logarithm (ln) of the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive normal-to-normal interval differences (RMSSD) HRV indices were utilised to establish intraclass correlation coefficient (ICC_2,1), coefficient of variation (%CV), and Pearson product-moment correlation (r). Results revealed the ICC values of HRV_ust lnSDNN (RSA_standard = 0.77-0.88; RSA_10%decrement = 0.41-0.71) and lnRMSSD (RSA_standard = 0.81-0.86; RSA_10%decrement = 0.57-0.82). Furthermore, significantly positive correlations between best sprint time and post-exercise HRV_ust indices were found in lnSDNN (r = 0.47-0.62; p < 0.05) and lnRMSSD (r = 0.45; p < 0.05). Additionally, a large CV of lnSDNN (RSA_standard = 32%-45%; RSA_10%decrement = 29%-39%), lnRMSSD (RSA_standard = 50%-66%; RSA_10%decrement = 48%-52%), and ratio (RSA_standard = 45%-126%; RSA_10%decrement = 27%-45%) was found after the RSA protocols. In conclusion, the number of bouts of RSA exercise potentially influences the agreement of post-exercise time-domain HRV_ust indices to standard HRV measure.

Objective: We sought to characterize the clinical prognostic factors in veterans with amyotrophic lateral sclerosis (ALS) followed in our ALS clinic.

Background: ALS is a rare, progressive neurodegenerative condition associated with decreased survival compared to that in the normal population.

Method: The electronic medical records of 105 veterans diagnosed with ALS who are followed in our ALS clinic between 2010 and 2021 were reviewed. Approval from the institutional review board was obtained from the study protocol. Demographic and clinical variables included age at symptom onset, age at initial evaluation, survival (from symptom onset to death), gender, site of onset (appendicular, bulbar, and respiratory), initial amyotrophic lateral sclerosis functional-related score-revised (ALSFRS-R), total functional independence measure (TFIM) scores, initial forced vital capacity (FVC), and interventions (Riluzole, gastrostomy, noninvasive ventilation [NIV], and tracheostomy). Normally distributed data was expressed as mean ± standard deviation. Fischer's exact analysis of the distribution differences of categorical data. The Kaplan-Meier plot analyzed the time-to-event.

Results: The mean (SD) age at symptom onset was 62.0 (11.1) years, age at diagnosis was 65 (11) years, with 72% of the patients being over 60 years at diagnosis. The median survival time from symptom onset was 4.12 (3) years. Limb-onset ALS (appendicular) was the most frequent (52%) followed by bulbar-onset ALS (43%). The mean ALSFRS-R and TFIM scores were 31 (8) and 91 (25), respectively. Family history (familial), bulbar, and respiratory presentation at diagnosis were associated with shorter survival times.

Conclusion: This study suggests that of the clinical prognostic factors veterans with familial ALS, bulbar, and respiratory onset at presentations had shorter survival. The presence of Agent Orange, PEG placement, and NIV did not affect survival.

This feasibility study evaluated the psychological status of patients with differentiated thyroid cancer (DTC) before, during, and 40 days after administration of I-131 radionuclide therapy (RAI). We investigated the appropriateness of providing patient a comprehensive psychological assessment in an isolation ward. Thirty consecutive patients (Study Group; SG) who received RAI were enrolled. The tools used were the Hospital Anxiety and Depression Scale (HADS) at three different moments, and the Coping Responses Inventory (CRI) at baseline for each patient. A supportive approach was also implemented. Data were collected at the first specialist visit, at the day of admission, and at 40 days follow-up visit. A matched cohort of patients (Control Group; CG), who did not receive psycho-oncological counseling, was retrospectively studied only about their medical needs and requests. Staff exposure to radiation was also compared during SG and CG hospitalization, to assess a possible reduction of radiological risk for them. A significant difference between the basal, intermediate, and final psychological status was observed (p < 0.0001), which was found to be irrespective of the induced hypothyroidism. Patients showed a significant worsening of their status in terms of anxiety and depression after the consent, but it improved 40 days after treatment. Repeated measures analysis showed a similar trend in patients' psychological status over this period. At hospital discharge, patients showed indirect signs of increased well-being. CG required more nursing and medical interventions. Staff exposure was significantly lower during hospitalization of SG as compared to CG. This study demonstrates that timed psychological evaluation and appropriate support may help to reduce anxiety and depression of patients receiving a diagnosis of cancer and undergoing RAI. Moreover, an improvement of workplace safety was recorded.

Background: The pressure fluctuation in the volute can be effectively reduced when the impeller of the double-suction pump is staggered, but the mechanism of this reduction is still unclear. At the same time, the traditional analysis method cannot realize the visualization of pressure fluctuation.

Objective: The purpose of this article is to explore the spatial distribution, propagation, and attenuation law of pressure fluctuation, and on this basis, to research the reason why staggered impeller reduce pressure fluctuation.

Methods: A new method called Pulse tracking network (PTN) was used in this article. Compared with the traditional method, which only analyzes the pressure fluctuation at scattered points, this method greatly improves the spatial resolution of the pressure fluctuation. In particular, the phase analysis is a major highlight of the method.

Results: Staggered impeller significantly reduced the pressure fluctuation intensity dominated by blade passing frequency. At the same time, the propagation of the pressure fluctuation in the volute changed from radial to circumferential in the volute cross-section.

Conclusions: Staggered impeller can effectively reduce pressure fluctuation, and the circumferential propagation caused by it is considered to be the main reason for it.

This study introduces an approach for converting the current from a sensor into controllable voltage. To this end, a switched-capacitor structure was integrated to provide efficient current-to-voltage conversion. The generated voltage was further regulated by an operational amplifier current source, enhancing stability and precision. An n-type metal oxide semiconductor field-effect transistor structure under an H-bridge was integrated into the system to achieve fine-tuned control over current stimulation. This component contributed to voltage regulation and enabled bi-directional control of current flow, offering versatility in adjusting current amplitudes using working and counter electrodes. This dynamic control mechanism was pivotal for effectively controlling the intensity of current stimulation. We applied Verilog-A modeling to simulate the optical characteristics of Si nanowires. The proposed system efficiently converted sensor-derived current into voltage using a switched-capacitor structure. Simultaneously, the precision was enhanced via operational amplifier regulation and n-type metal-oxide-semiconductor field-effect transistor-based H-bridge control. The simulation showed a current stimulus amplitude ranging from 2 to 13 μA for a variable photocurrent of Si nanowires (Rex: 10 kΩ, pulse: 100 Hz, 1 ms). The ability to finely control current stimulation intensity holds promise for diverse applications requiring accurate and adjustable current manipulation. This study contributes to the growing field of sensor technology by offering a unique perspective on the integration of nanostructures and electronic components for an enhanced control and functionality.