Proteolytic activation of angiomotin by DDI2 promotes angiogenesis.

The scaffolding protein angiomotin (AMOT) is indispensable for vertebrate embryonic angiogenesis. Here, we report that AMOT undergoes cleavage in the presence of lysophosphatidic acid (LPA), a lipid growth factor also involved in angiogenesis. AMOT cleavage is mediated by aspartic protease DNA damage-inducible 1 homolog 2 (DDI2), and the process is tightly regulated by a signaling axis including neurofibromin 2 (NF2), tankyrase 1/2 (TNKS1/2), and RING finger protein 146 (RNF146), which induce AMOT membrane localization, poly ADP ribosylation, and ubiquitination, respectively. In both zebrafish and mice, the genetic inactivation of AMOT cleavage regulators leads to defective angiogenesis, and the phenotype is rescued by the overexpression of AMOT-CT, a C-terminal AMOT cleavage product. In either physiological or pathological angiogenesis, AMOT-CT is required for vascular expansion, whereas uncleavable AMOT represses this process. Thus, our work uncovers a signaling pathway that regulates angiogenesis by modulating a cleavage-dependent activation of AMOT.

C-Reactive Protein: The Most Familiar Stranger.

C-reactive protein (CRP) is a highly conserved pentraxin with pattern recognition receptor-like activities. However, despite being used widely as a clinical marker of inflammation, the in vivo functions of CRP and its roles in health and disease remain largely unestablished. This is, to certain extent, due to the drastically different expression patterns of CRP in mice and rats, raising concerns about whether the functions of CRP are essential and conserved across species and how these model animals should be manipulated to examine the in vivo actions of human CRP. In this review, we discuss recent advances highlighting the essential and conserved functions of CRP across species, and propose that appropriately designed animal models can be used to understand the origin-, conformation-, and localization-dependent actions of human CRP in vivo. The improved model design will contribute to establishing the pathophysiological roles of CRP and facilitate the development of novel CRP-targeting strategies.

A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration.

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.

Long-distance transport of sucrose in source leaves promotes sink root growth by the EIN3-SUC2 module.

In most plants, sucrose, a major storage sugar, is transported into sink organs to support their growth. This key physiological process is dependent on the function of sucrose transporters. Sucrose export from source tissues is predominantly controlled through the activity of SUCROSE TRANSPORTER 2 (SUC2), required for the loading of sucrose into the phloem of Arabidopsis plants. However, how SUC2 activity is controlled to support root growth remains unclear. Glucose is perceived via the function of HEXOKINASE 1 (HXK1), the only known nuclear glucose sensor. HXK1 negatively regulates the stability of ETHYLENE-INSENSITIVE3 (EIN3), a key ethylene/glucose interaction component. Here we show that HXK1 functions upstream of EIN3 in the regulation of root sink growth mediated by glucose signaling. Furthermore, the transcription factor EIN3 directly inhibits SUC2 activity by binding to the SUC2 promoter, regulating glucose signaling linked to root sink growth. We demonstrate that these molecular components form a HXK1-EIN3-SUC2 module integral to the control of root sink growth. Also, we demonstrate that with increasing age, the HXK1-EIN3-SUC2 module promotes sucrose phloem loading in source tissues thereby elevating sucrose levels in sink roots. As a result, glucose signaling mediated-sink root growth is facilitated. Our findings thus establish a direct molecular link between the HXK1-EIN3-SUC2 module, the source-to sink transport of sucrose and root growth.

Intermittent Theta-Burst Stimulation for Stroke: Primary Motor Cortex Versus Cerebellar Stimulation: A Randomized Sham-Controlled Trial.

BACKGROUND: Stroke survivors with impaired balance and motor function tend to have relatively poor functional outcomes. The cerebellum and primary motor cortex (M1) have been suggested as targets for neuromodulation of balance and motor recovery after stroke. This study aimed to compare the efficacy and safety of intermittent theta-burst stimulation (iTBS) to the cerebellum or M1 on balance and motor recovery in patients with stroke. METHODS: In this randomized, double-blind, sham-controlled clinical trial, patients with subacute stroke were randomly divided into 3 groups: M1-, cerebellar-, and sham-iTBS (n=12 per group; 15 sessions, 3 weeks). All outcomes were evaluated before intervention (T0), after 1 week of intervention (T1), after 3 weeks of intervention (T2), and at follow-up (T3). The primary outcome was the Berg balance scale score at T2. Secondary outcomes include the Fugl-Meyer assessment scale for lower extremities, the trunk impairment scale, the Barthel index, the modified Rankin Scale, the functional ambulation categories, and cortical excitability. RESULTS: A total of 167 inpatients were screened, 36 patients (age, 57.50±2.41 years; 10 women, 12 ischemic) were enrolled between December 2020 and January 2023. At T2, M1- or cerebellar-iTBS significantly improved Berg balance scale scores by 10.7 points ([95% CI, 2.7-18.6], P=0.009) and 14.2 points ([95% CI, 1.2-27.2], P=0.032) compared with the sham-iTBS group. Moreover, the cerebellar-iTBS group showed a significantly greater improvement in Fugl-Meyer assessment scale for lower extremities scores by 5.6 points than the M1-iTBS ([95% CI, 0.3-10.9], P=0.037) and by 7.8 points than the sham-iTBS ([95% CI, 1.1-14.5], P=0.021) groups at T2. The motor-evoked potential amplitudes of the M1- and cerebellar-iTBS groups were higher than those of the sham-iTBS group (P<0.001). CONCLUSIONS: Both M1- and cerebellar-iTBS could improve balance function. Moreover, cerebellar-iTBS, but not M1-iTBS, induced significant effects on motor recovery. Thus, cerebellar-iTBS may be a valuable new therapeutic option in stroke rehabilitation programs. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2100047002.

Continuously tunable single-photon level nonlinearity with Rydberg state wave-function engineering.

Extending optical nonlinearity into the extremely weak light regime is at the heart of quantum optics, since it enables the efficient generation of photonic entanglement and implementation of photonic quantum logic gate. Here, we demonstrate the capability for continuously tunable single-photon level nonlinearity, enabled by precise control of Rydberg interaction over two orders of magnitude, through the use of microwave-assisted wave-function engineering. To characterize this nonlinearity, light storage and retrieval protocol utilizing Rydberg electromagnetically induced transparency is employed, and the quantum statistics of the retrieved photons are analyzed. As a first application, we demonstrate our protocol can speed up the preparation of single photons in low-lying Rydberg states by a factor of up to∼40. Our work holds the potential to accelerate quantum operations and to improve the circuit depth and connectivity in Rydberg systems, representing a crucial step towards scalable quantum information processing with Rydberg atoms.

Resting-State fMRI Study of Vigilance Under Circadian and Homeostatic Modulation Based on Fractional Amplitude of Low-Frequency Fluctuation and Regional Homogeneity in Humans Under Normal Entrained Conditions.

BACKGROUND: How brain neural activity changes at multiple time points throughout the day and the neural mechanisms underlying time-dependent modulation of vigilance are less clear. PURPOSE: To explore the effect of circadian rhythms and homeostasis on brain neural activity and the potential neural basis of time-dependent modulation of vigilance. STUDY TYPE: Prospective. SUBJECTS: A total of 30 healthy participants (22-27 years old). FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted imaging, echo-planar functional MRI (fMRI). ASSESSMENT: Six resting-state fMRI (rs-fMRI) scanning sessions were performed at fixed times (9:00 h, 13:00 h, 17:00 h, 21:00 h, 1:00 h, and 5:00 h) to investigate fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) diurnal variation. The fALFF/ReHo and the result of the psychomotor vigilance task were used to assess local neural activity and vigilance. STATISTICAL TESTS: One-way repeated measures analysis of variance (ANOVA) was used to assess changes in vigilance (P < 0.05) and neural activity in the whole brain (P < 0.001 at the voxel level and P < 0.01 at the cluster level, Gaussian random field [GRF] corrected). Correlation analysis was used to examine the relationship between neural activity and vigilance at all-time points of the day. RESULTS: The fALFF/ReHo in the thalamus and some perceptual cortices tended to increase from 9:00 h to 13:00 h and from 21:00 h to 5:00 h, whereas the key nodes of the default mode network (DMN) tended to decrease from 21:00 h to 5:00 h. The vigilance tended to decrease from 21:00 h to 5:00 h. The fALFF/ReHo in the thalamus and some perceptual cortices was negatively correlated with vigilance at all-time points of the day, whereas the fALFF/ReHo in the key nodes of the DMN was positively correlated with vigilance. DATA CONCLUSION: Neural activities in the thalamus and some perceptual cortices show similar trends throughout the day, whereas the key nodes of the DMN show roughly opposite trends. Notably, diurnal variation of the neural activity in these brain regions may be an adaptive or compensatory response to changes in vigilance. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: 1.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.

Diurnal variation of cerebral blood flow in healthy humans under normal entrained conditions.

The presence of a circadian cycle of cerebral blood flow may have implications for the occurrence of daily variations in cerebrovascular events in humans, but how cerebral blood flow varies throughout the day and its mechanism are still unclear. The study aimed to explore the diurnal variation of cerebral blood flow in healthy humans and its possible mechanisms. Arterial spin labelling images were collected at six time-points (09:00 hours, 13:00 hours, 17:00 hours, 21:00 hours, 01:00 hours, 05:00 hours) from 18 healthy participants (22-39 years old; eight females) to analyse diurnal variations in cerebral blood flow. Resting heart rate and blood pressure at six time-points and blood indicators (20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids, prostaglandin E2, noradrenaline and nitric oxide) related to cerebral vascular tone at two time-points (09:00 hours and 21:00 hours) were collected to analyse possible influences on diurnal variations in cerebral blood flow. From 21:00 hours to 05:00 hours, parietal cortical relative cerebral blood flow tended to increase, while frontal cortical and cerebellar relative cerebral blood flow tended to decrease. There was a time-dependent negative correlation between parietal cortical relative cerebral blood flow and resting heart rate, whereas there was a time-dependent positive correlation between cerebellar relative cerebral blood flow and resting heart rate. The change of parietal cortical relative cerebral blood flow was positively correlated with the change of nitric oxide. There was also a time-dependent positive correlation between mean arterial pressure and mean whole-brain cerebral blood flow. The findings indicated that parietal cortical relative cerebral blood flow and frontal cortical/cerebellar relative cerebral blood flow showed roughly opposite trends throughout the day. The diurnal variations in relative cerebral blood flow were regional-specific. Diurnal variation of nitric oxide and neurogenic regulation may be potential mechanisms for diurnal variation in regional relative cerebral blood flow.

Changes in pituitary adenoma patient presentation and outcomes during the COVID pandemic at a Pituitary Center of Excellence.

PURPOSE: The COVID-19 pandemic caused significant disruption to the surgical care of patients. The aim of this study was to analyze the impact of the pandemic on endoscopic endonasal surgery (EES) for patients with a pituitary adenoma. METHODS: Patients from 2015 to 2022 that had EES for a pituitary adenoma were included in this study. Patients were separated into pre-COVID (January 2015-March 2020) and COVID (March 2020-September 2022) groups. Univariate analysis was done using chi-square, fisher exact tests, and t-tests to compare groups. RESULTS: This study included 492 patients that had EES for their pituitary adenoma. There were 314 patients in the pre-COVID group and 178 patients in the COVID group. Patients in the COVID group had a higher risk analysis index (RAI) frailty score (15 ± 10 pre-COVID vs. 20 ± 9 COVID, P < 0.001) and a higher American Society of Anesthesiology (ASA) physical status score (3 or 4) (72.0% pre-COVID vs. 81.9% COVID, P = 0.02). There were significantly more macroadenoma cases (87.6% pre-COVID vs. 94.4% COVID, P = 0.02) and extrasellar surgical approaches (45.2% pre-COVID vs. 61.2% COVID, P < 0.001) during COVID. There was no significant difference in length of stay (LOS) and readmission rates between groups. CONCLUSIONS: Patients that presented during the pandemic tended to be more frail, have more comorbidities, and require additional extrasellar surgical approaches. Despite changes in clinical presentation and operative management, the LOS and readmission rate remained stable during COVID, supporting the safety of this procedure during the recent pandemic.

Retrospective Analysis of Adverse Factors Impacting Medicine Logistics.

Background: Medicine logistics, particularly cryogenic storage, maintains pharmaceutical efficacy and safety. Ensuring seamless transportation and storage prevents spoilage, degradation, or contamination, safeguarding patient health. Objective: This study aimed to analyze the relationships among the components of the medication cold chain logistics system using grey relational analysis (GRA). Additionally, we utilized GRA to construct an adjacency matrix, facilitating a comprehensive understanding of the interdependencies within the system. Methods: Data from pertinent indices spanning 2021 and 2022 were utilized to conduct a quantitative analysis using GRA. This analysis aimed to identify the most influential elements affecting the growth of pharmaceutical cold chain logistics in a specific location. The negative aspects of the medication cold chain logistics system in particular areas were examined by assessing the grey relationship grades between various components and the medicine cold chain logistics system in those regions. Results: The analysis revealed significant insights into the correlated risk factors impacting medicine logistics operations. Through an examination of the financial status and operational processes of medicine logistics assets, four categories of risks were identified, encompassing transportation, storage, distribution, and quality management. These categories were established by analyzing the most significant risk factors across these operational domains. Additionally, GRA was employed to assess the factors influencing medicine logistics. The study found a strong relationship between key parameters, such as transportation risk and site facilities and equipment, and the growth of the pharmaceutical logistics sector. Operation risk emerged as the least influential factor, while site facilities and equipment, transportation risk, and operation risk demonstrated substantial influence on the region's medical logistics sector growth. Conclusion: This study provides important recommendations to improve medicine logistics, aiming to mitigate adverse effects and elevate inventory management. Implementation can enhance efficiency and safety in the medicine supply chain, benefiting patient care and public health.

Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

PURPOSE: The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. METHODS: Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. RESULTS: Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9 ± 18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. CONCLUSIONS: The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.

Evaluation of two laboratory model methods for diarrheal irritable bowel syndrome.

BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. METHODS: The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. RESULTS: Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1ß, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. CONCLUSION: In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling.

Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications.

BACKGROUND AND PURPOSE: Patients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG). METHODS: We performed a retrospective single-center cohort study and analyzed outcomes and complications after PGR of the TG. Clinical outcome after PGR of the TG was assessed via the Barrow Neurological Institute (BNI) Pain Scale. RESULTS: Forty-five patients underwent a total of 66 PGRs of the TG. At short-term follow-up, 58 procedures (87.9%) resulted in a BNI score of I (i.e., freedom from pain without medication). At a median follow-up of 3.07 years, 18 procedures (27.3%) resulted in a BNI score of I, 12 procedures (18.1%) resulted in BNI score of IIIa, and 36 procedures (54.5%) resulted in a BNI score of IIIb-V. The median length of freedom from pain without medication was 1.5 years. Eighteen procedures (27.3%) caused hypesthesia and two (3.0%) caused paresthesias. There were no serious complications. CONCLUSION: In patients with these anatomical subtypes of TN there was a high rate of short-term pain relief for the first 1-2 years and thereafter a large proportion of patients experienced pain relapse. In this patient group, PGR of the TG represents a safe procedure that is efficacious in the short term.

Pharmacokinetic profile of irinotecan in patients with chronic kidney disease: Two cases and literature review.

AIMS: There are limited pharmacokinetic data on the use of irinotecan in patients with reduced glomerular filtration rate (GFR) and no haemodialysis. In this case report, we present 2 cases and review the current literature. METHODS: The dose of irinotecan in both patients was reduced pre-emptively due to reduced GFR. The first patient had her irinotecan dose reduced to 50%, but was nevertheless admitted to hospital because of irinotecan-induced toxicity, including gastrointestinal toxicity and neutropenic fever. The dose was reduced further to 40% for the second cycle; however, the patient was again admitted to the hospital, and irinotecan was stopped indefinitely. The second patient also had his irinotecan dose reduced to 50% and was admitted to the emergency department for gastrointestinal toxicity after the first cycle. However, irinotecan could be administered in the same dose in later cycles. RESULTS: The area under the curve to infinity of irinotecan and SN-38 in the first patient were comparable to those of an individual receiving 100% dose intensity. The area under the curve to infinity of irinotecan and SN-38 in patient 2 in both cycles were slightly less than reference values. Furthermore, clearance values of irinotecan and SN-38 in our patients were comparable to those without renal impairment. CONCLUSION: Our case report suggests that reduced GFR may not significantly affect the clearance of irinotecan and SN-38, but can still result in clinical toxicity. Reduced initial dosing seems indicated in this patient population. Further research is needed to fully understand the relationship between reduced GFR, pharmacokinetics, and toxicity of irinotecan and SN-38.

Altered static and dynamic indices of intrinsic brain activity in patients with subcortical ischemic vascular disease: a resting-state functional magnetic resonance imaging analysis.

PURPOSE: To explore the static and dynamic characteristics of intrinsic brain activity (IBA) in subcortical ischemic vascular disease (SIVD) patients with or without cognitive impairment. METHODS: In total, 90 participants were recruited, including 32 SIVD patients with cognitive impairment (SIVD-CI, N = 32), 26 SIVD patients with no cognitive impairment (SIVD-NCI, N = 26), and 32 healthy controls (HC, N = 32) matched for age, gender, and education. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and neuropsychological tests. Amplitude of low-frequency fluctuation (ALFF) was calculated to reflect static alterations of regional IBA. Sliding window analysis was conducted in order to explore the dynamic characteristics. RESULTS: Both SIVD-CI and SIVD-NCI group showed significantly decreased ALFF in left angular gyrus (ANG), whereas SIVD-CI group showed increased ALFF in right superior frontal gyrus (SFG), compared with HCs. Furthermore, SIVD-CI group showed significantly decreased ALFF dynamics (dALFF) in right precuneus (PreCu) and left dorsal anterior cingulate cortex (dACC), compared with HC and SIVD-NCI groups (Gaussian random field-corrected, voxel-level P < 0.001, cluster-level P < 0.05). No dynamic changes were detected between SIVD-NCI group and HC group. The mean ALFF value in left ANG of SIVD-CI group was correlated with the score of delayed memory scale. CONCLUSION: ANG may be a vulnerable brain region in SIVD patients. Temporal dynamic analysis could serve as a sensitive and promising method to investigate IBA alterations in SIVD patients.

Tumor-derived autophagosome vaccines combined with immune adjuvants mediate antitumor immune responses via the neoantigen pathway.

Vaccines composed of autophagosomes derived from tumor cells called DRibbles (DRiPs-containing blebs) are involved in the cross-presentation of tumor antigens, thus inducing cross-reactive T-cell responses against the tumor. Compared with traditional tumor lysate vaccines, autophagosome vaccines were found to be better sources of multiple tumor-associated antigens (TAAs) that activate antigen-specific T-cells. However, the involvement of tumor neoantigens in the immune responses of autophagosome vaccines remains unclear. The present study showed that exogenous autophagosome vaccines (DRibbles) combined with immune adjuvants (anti-OX40 antibody and ATP) can effectively activate functional T cells in vitro. Importantly, the combination of exogenous tumor-derived autophagosome vaccines and immune adjuvants was found to induce tumor regression in B16F10 and 4T1 tumor-bearing mice. The combination of autophagosome-enriched DRibbles with anti-OX40 antibody and ATP also exhibited optimal immune stimulation and antitumor efficiency in vivo. The effectiveness of exogenous DRibble vaccines was mainly due to their enhancement of tumor immunogenicity by increasing the presentation and release of tumor neoantigens. These findings suggest that this immunotherapeutic method may be effective in the treatment of cancer.

State-of-the-Art Review on Amorphous Carbon Nanotubes: Synthesis, Structure, and Application.

Carbon nanotubes (CNTs) have rapidly received increasing attention and great interest as potential materials for energy storage and catalyst fields, which is due to their unique physicochemical and electrical properties. With continuous improvements in fabrication routes, CNTs have been modified with various types of materials, opening up new perspectives for research and state-of-the-art technologies. Amorphous CNTs (aCNTs) are carbon nanostructures that are distinctively different from their well-ordered counterparts, such as single-walled and multi-walled carbon nanotubes (SWCNTs and MWCNTs, respectively), while the atoms in aCNTs are grouped in a disordered, crystalline/non-crystalline manner. Owing to their unique structure and properties, aCNTs are attractive for energy storage, catalysis, and aerospace applications. In this review, we provide an overview of the synthetic routes of aCNTs, which include chemical vapor deposition, catalytic pyrolysis, and arc discharge. Detailed morphologies of aCNTs and the systematic elucidation of tunable properties are also summarized. Finally, we discuss the future perspectives as well as associated challenges of aCNTs. With this review, we aim to encourage further research for the widespread use of aCNTs in industry.

In2S3@TiO2/In2S3 Z-Scheme Heterojunction with Synergistic Effect for Enhanced Photocathodic Protection of Steel.

In this work, a TiO2/In2S3 heterojunction film was successfully synthesized using a one-step hydrothermal method and applied in the photocathodic protection (PCP) of 304SS. The octahedral In2S3 and In2S3@TiO2 nanoparticles combined and coexisted with each other, with In2S3 quantum dots growing on the surface of TiO2 to form In2S3@TiO2 with a wrapping structure. The composite photoelectrode, which includes TiO2 with a mixed crystalline phase and In2S3, exhibited significantly enhanced PCP performance for 304SS compared with pure In2S3 and TiO2. The In2S3@TiO2/In2S3 composites with 0.3 g of P25 titanium dioxide (P25) showed the best protection performance, resulting in a cathodic shift of its OCP coupled with 304SS to -0.664 VAgCl. The electron transfer tracking results demonstrate that In2S3@TiO2/In2S3 forms a Z-scheme heterojunction structure. The enhanced PCP performance could be attributed to the synergistic effect of the mixed crystalline phase and the Z-scheme heterojunction system. The mixed crystalline phase of TiO2 provides more electrons, and these electrons are gathered at higher energy potentials in the Z-scheme system. Additionally, the built-in electric field further promotes the more effective electrons transfer from photoelectrode to the protected metals, thus, leading to enhanced photoelectrochemical cathodic protection of 304SS.

Correlations between moral courage, moral sensitivity, and ethical decision-making by nurse interns: a cross-sectional study.

BACKGROUND: Clinical decision-making involves ethical issues that become more and more complex. Nurse interns must be more skilled in making rational and timely decisions when facing ethical dilemmas. The contributing factors and their relationships that challenge ethical decision-making among nurse interns must be fully understood, as this level of knowledge can support the development of strategies and interventions that improve the ethical decision-making ability of nurse interns. OBJECTIVE: This study examined the relationships between moral courage, moral sensitivity, and ethical decision-making by nurse interns. In addition, we investigated whether moral sensitivity mediates the relationship between moral courage and ethical decision-making. DESIGN: A descriptive cross-sectional study using an online questionnaire. SETTING: The study sampled nurse interns from Class iii Grade A general hospitals in Sichuan Province, China. PARTICIPANTS: A convenience sampling method was used to select 1334 nurse interns from March 2022 to May 2022. METHODS: A general information questionnaire, the Nurses' Moral Courage Scale (NMCS), the Chinese Moral Sensitivity Questionnaire (MSQ), and the Judgement About Nursing Decision (JAND) were used for data collection. Data was processed and analysed using SPSS 26.0 and Amos 28.0. Data analysis included descriptive statistics, Pearson correlation analysis, and structural equation modelling. RESULTS: Moral courage was found to be positively correlated with ethical decision-making (P < 0.01). Moral sensitivity was also positively correlated with ethical decision-making (P < 0.01) and had a mediating effect on the relationship between moral courage and ethical decision-making (P < 0.01). CONCLUSIONS: The moral courage and moral sensitivity of nurse interns are positively correlated with ethical decision-making ability. Moral sensitivity significantly mediates the relationship between moral courage and ethical decision-making ability. The knowledge gained from this study can inform educational strategies and interventions in supporting the development of nurse interns' ethical decision-making ability.