Levosimendan: A New Therapeutical Strategy in Patients with Renal Insufficiency.

Levosimendan, a Ca2 + sensitizer with positive inotropic effects, is primarily employed for the short-term treatment of acute decompensated heart failure (ADHF). Levosimendan exerts renal function protection through various mechanisms, including anti-apoptosis, anti-inflammatory, and antioxidant effects in vivo. Additionally, levosimendan may have a protective effect on individuals with heart failure and renal insufficiency, as well as on renal function impairment after cardiac surgery. However, the application of levosimendan in patients with severe renal dysfunction remains controversial. This article delves into the use of levosimendan in severe renal insufficiency, explores its impact on renal function, and provides a comprehensive overview of its impact on renal function after cardiac surgery.

Light People: Prof. Donal D C Bradley (FRS).

EDITORIAL: The invention of organic light emitting diodes (LEDs) led to enormous excitement in both academe and industry in the late 1980's. Flexibility, large area solution processability, roll-to-roll printing, low cost, and environmentally friendly are some of the advantages of organic semiconductor materials, which brought a new horizon for optoelectronics. Together with the achievement of organic solar cells, transistors, lasers, and amplifiers, this has demonstrated potential applications of organic semiconductors in displays, lighting, solar energy generation, electronics, sensing and imaging, and many aspects of photonics. In an enlightened conversation with Light: Science & Applications, Prof. Donal Bradley (FRS), a pioneer in the field, shared his deep insights on past, current, and future exciting developments of organic optoelectronic materials and devices. In particular, he expressed his opinion on the hot topics related to organic optoelectronics research and application, such as the relationship between organic and inorganic semiconductors and the challenge of electrically pumped organic lasers. As a successful scientist, Donal has also been co-founder of several organic optoelectronics innovation companies and research centers and a long-term academic administrator serving as a Head of Department, Centre Director, and Vice-Rector for Research at Imperial College, Head of the Mathematical, Physical, and Life Sciences Division at the University of Oxford, Vice-President for Research at King Abdullah University of Science and Technology and now Vice-President for Research and Innovation at NEOM U and Executive Director of the NEOM Education, Research and Innovation Foundation. Through this interview, we also explore the major roles and events in Donal's career experience from the invention of the first conjugated polymer LED in the world to the set-up of entrepreneurial companies, from Cambridge to Sheffield, Imperial College, and Oxford, from the UK to overseas, and from the establishment of the Centre for Plastic Electronics in Imperial College to the set-up of the Oxford Suzhou Centre for Advanced Research (OSCAR). Before the end of the conversation, he also shares his interesting story of identifying a new species of Sea Bream, Acanthopagrus oconnorae (Bev Bradley's Bream), named after his mother and wife, while fishing in the Red Sea.

Inverse association between serum chloride levels and the risk of atrial fibrillation in chronic kidney disease patients.

Background: Electrolyte abnormalities are common symptoms of chronic kidney disease (CKD), but previous studies have mainly focussed on serum potassium and sodium levels. Chloride is an important biomarker for the prognosis of various diseases. However, the relationship between serum chloride levels and atrial fibrillation (AF) in CKD patients is unclear. Objective: In this study, we sought to determine the association between serum chloride homeostasis and AF in CKD patients. Methods: In this retrospective cohort study, we included patients who met the diagnostic criteria for CKD in China between 2000 and 2021. Competing risk regression for AF was performed. The associations of the baseline serum chloride concentration with heart failure (HF) and stroke incidence were also calculated by competing risk regression. The association of baseline serum chloride levels with all-cause death was determined by a Cox regression model. Results: The study cohort comprised 20 550 participants. During a median follow-up of 350 days (interquartile range, 123-730 days), 211 of the 20 550 CKD patients developed AF. After multivariable adjustment, every decrease in the standard deviation of serum chloride (5.02 mmol/l) was associated with a high risk for AF [sub-hazard ratio (sHR) 0.78, 95% confidence interval (CI) 0.65-0.94, P = .008]. These results were also consistent with those of the stratified and sensitivity analyses. According to the fully adjusted models, the serum chloride concentration was also associated with a high risk for incident HF (sHR 0.85, 95% CI 0.80-0.91, P < .001), a high risk for incident stroke (sHR 0.87, 95% CI 0.81-0.94, P < .001), and a high risk for all-cause death [hazard ratio (HR) 0.82, 95% CI 0.73-0.91, P < .001]. Conclusion: In this CKD population, serum chloride levels were independently and inversely associated with the incidence of AF. Lower serum chloride levels were also associated with an increased risk of incident HF, stroke, and all-cause death.

Stimulation by exosomes from hypoxia-preconditioned hair follicle mesenchymal stem cells facilitates mitophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to alleviate ulcerative colitis.

Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.

Protective effect of Cordycepin on blood-testis barrier against pre-puberty polystyrene nanoplastics exposure in male rats.

Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.

A machine learning model utilizing delphian lymph node characteristics to predict contralateral central lymph node metastasis in papillary thyroid carcinoma: A prospective multicenter study.

BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.

GABPA-Mediated Expression of HPN-AS1 Facilitates Cell Apoptosis and Inhibits Cell Proliferation in Hepatocellular Carcinoma by Promoting eIF4A3 Degradation.

Hepatocellular carcinoma (HCC) represents a common neoplasm that presents a substantial worldwide health challenge. Nevertheless, the involvement of HPN-AS1 in HCC remains unknown. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was utilized to measure HPN-AS1 expression in HCC. The GABPA effects on the HPN-AS1 promoter were analyzed through chromatin immunoprecipitation and luciferase reporter assays. Cell proliferation potential was determined by deploying CCK-8 assay, Ki-67 immunofluorescence staining, and colony formation assay. Cell apoptosis was detected using acridine orange/ethidium bromide staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Western blotting was utilized to measure the protein levels of proliferation factors and apoptosis regulators. HPN-AS1 binding to eIF4A3 was accessed by RNA-binding protein immunoprecipitation assay. HPN-AS1 was significantly downregulated in both HCC cells and tissues. Lower HPN-AS1 levels indicate a poorer HCC prognosis. Moreover, we found that GABPA functions as a transcription factor for HPN-AS1. Functional studies revealed that HPN-AS1 displayed inhibitory effects on HCC cell proliferation and promoted apoptosis. Mechanically, HPN-AS1 bound to and facilitated translation initiation factor eIF4A3 degradation. Loss of HPN-AS1 augmented eIF4A3 protein levels rather than eIF4A3 mRNA levels. Exogenous expression of eIF4A3 could restore eIF4A3 protein levels and reverse HPN-AS1 overexpression-induced cell proliferation inhibition and cell apoptosis. Our study elucidated that HPN-AS1 downregulation was mediated by GABPA. HPN-AS acted as a tumor suppressor within HCC through binding and facilitating eIF4A3 degradation. The study provides a novel insight into the biological function of HPN-AS1 in HCC, suggesting that HPN-AS1 could be a promising biomarker and a potential target for HCC diagnosis and treatment.

Advances of surgical robotics: image-guided classification and application.

Surgical robotics application in the field of minimally invasive surgery has developed rapidly and has been attracting increasingly more research attention in recent years. A common consensus has been reached that surgical procedures are to become less traumatic and with the implementation of more intelligence and higher autonomy, which is a serious challenge faced by the environmental sensing capabilities of robotic systems. One of the main sources of environmental information for robots are images, which are the basis of robot vision. In this review article, we divide clinical image into direct and indirect based on the object of information acquisition, and into continuous, intermittent continuous, and discontinuous according to the target-tracking frequency. The characteristics and applications of the existing surgical robots in each category are introduced based on these two dimensions. Our purpose in conducting this review was to analyze, summarize, and discuss the current evidence on the general rules on the application of image technologies for medical purposes. Our analysis gives insight and provides guidance conducive to the development of more advanced surgical robotics systems in the future.

Chromosome-level assembly and evolution analysis of the Trichosanthes truncata genome.

Trichosanthes truncata C. B. Clarke, an important medicinal plant, is a dioecious plant belonging to the Cucurbitaceae family. This study presents a chromosomal-level reference genome assembly for T. truncata. Through the integration of PacBio high-fidelity sequencing and high-throughput chromosome conformation capture technology, a final genome sequence of 637.41 Mb was assembled, with an N50 of 57.24 Mb and consisting of 11 pseudochromosomes. Additionally, 97.21 Mb of repetitive sequences and 36,172 protein-coding genes were annotated. This high-quality genome assembly is of utmost significance for studying the molecular mechanisms underlying the biosynthesis of bioactive compounds. Furthermore, this study provided valuable insights into plant comparative genomics research.

Exploring Cognitive Related Microstructural Alterations in Normal Appearing White Matter and Deep Grey Matter for Small Vessel Disease: A Quantitative Susceptibility Mapping Study.

Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.

Experiences of Chinese Rheumatoid Arthritis Patients Who Chose Western Medicine, Traditional Chinese Medicine, and a Combination of Treatments: A Study Based on Interviews and Thematic Analysis.

Background: This qualitative study, part of a prospective mixed-methods research, aimed to gain insights into the medical experiences and disease perceptions of Chinese patients living with rheumatoid arthritis (RA). Specifically, the study examined how RA patients' perceptions of their disease were influenced by the diagnosis and treatment they receive. Methods: RA patients undergoing treatment were invited to participate in this qualitative study. Face-to-face semi-structured interviews were conducted among 18 patients, and the collected data were analyzed using thematic analysis. Results: The 18 participants in this study had a mean (SD) age of 58, a median disease duration of 6.5 years, and a predominance of female subjects (17 out of 18). The qualitative analysis identified two themes with six sub-themes: 1. Patients' experiences of treatment: discovery of the disease, misdiagnosis and mistreatment, and patients' treatment choices; 2. Feelings about the disease: psychological impact, reflections on the disease, and expectations of treatment. Conclusion: This study provides valuable perspectives and data to enhance the understanding of the relationship between patients' illness perceptions and their healthcare choices.

Exceptional Nexus in Bose-Einstein Condensates with Collective Dissipation.

In multistate non-Hermitian systems, higher-order exceptional points and exotic phenomena with no analogues in two-level systems arise. A paradigm is the exceptional nexus (EX), a third-order EP as the cusp singularity of exceptional arcs (EAs), that has a hybrid topological nature. Using atomic Bose-Einstein condensates to implement a dissipative three-state system, we experimentally realize an EX within a two-parameter space, despite the absence of symmetry. The engineered dissipation exhibits density dependence due to the collective atomic response to resonant light. Based on extensive analysis of the system's decay dynamics, we demonstrate the formation of an EX from the coalescence of two EAs with distinct geometries. These structures arise from the different roles played by dissipation in the strong coupling limit and quantum Zeno regime. Our Letter paves the way for exploring higher-order exceptional physics in the many-body setting of ultracold atoms.

Probing the interfacial behaviors of interfacially active and non-active asphaltenes and their impact on emulsion stability.

HYPOTHESIS: Asphaltenes subfractions with distinct interfacial behaviors may play different roles in stabilizing oil-water emulsions. EXPERIMENTS: In this work, whole asphaltenes were separated into interfacially active asphaltenes (IAA) and interfacially non-active asphaltenes (INAA). Employing advanced nanomechanical techniques, we have explored the compositions, morphologies, sizes, adsorption, and interfacial behaviors of IAA and INAA. FINDINGS: IAA exhibits a high and unevenly distributed oxygen content, distinguishing it from INAA. In toluene, the diameters of IAA and INAA are about 60 nm and 6 nm, respectively. When adsorbed irreversibly on mica surfaces, the thickness of the IAA and INAA film was measured at âˆ¼5.5 nm or 1 nm, respectively; while in a toluene solution, the film thickness reached âˆ¼46 nm and 3.1 nm for IAA and INAA, respectively. IAA demonstrates superior interfacial activity, and elastic/viscous moduli compared to INAA at the water-toluene interface. Quantified surface force measurements reveal that IAA stabilizes water droplets in toluene at a concentration of only 10 mg/L, while INAA requires a higher concentration of 100 mg/L. This work provides the first comprehensive investigation into the adsorption and interfacial behaviors of asphaltene subfractions and provides useful insights into the asphaltenes-stabilization mechanism of emulsions.

Mutualistic Synthesis from Orthogonal Dynamic Covalent Reactions.

Mutualisms are interactions that benefit all species involved. It has been widely investigated in neighbouring subjects, such as biology, ecology, sociology, and economics. However, such a reciprocal relationship in synthetic chemical systems has rarely been studied. Here, we demonstrate a mutualistic synthesis where byproducts from two orthogonal chemical reactions aid each other's production. Disulfide exchange and hydrazone exchange were chosen to generate two dynamic combinatorial libraries. A minor tetrameric macrocycle from the active disulfide library was quantitatively amplified in the presence of the hydrazone library. This incorporation also turned on the previously inert hydrazone reaction, producing a linear species that formed a "handcuffs" catenane with the disulfide tetramer. These findings not only lend robust support to the hypothesis of "RNA-peptide coevolution" for the origin of life but also broaden the scope of synthetic chemistry, highlighting the untapped potential of minor products from different reactions. Additionally, the co-self-assembly of these mutualistic entities to form supramolecular structures opens new avenues for future development of composite nanosystems with synergistic properties.

CIAO1 loss of function causes a neuromuscular disorder with compromise of nucleocytoplasmic Fe-S enzymes.

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.

[Estrogen receptor Esr1 induces early ovarian differentiation in Trachemys scripta].

This study aims to explore the roles of three estrogen receptors (Esr1, Esr2, and Gper1) in early differentiation of embryonic gonads of Trachemys scripta. The expression characteristics of the receptor genes were studied first. The Esr1, Esr2, and Gper1 agonists PPT, WAY 200070, and G-1 were respectively injected into the embryos at the male-producing temperature (MPT) before initiation of gonadal differentiation. The sex reversal of the treated embryonic gonads was analyzed in terms of morphological structure of gonads, distribution pattern of germ cells, and expression of key genes and proteins involved in sex differentiation. The expression level of esr1 during the critical stage of sex differentiation was higher than those of esr2 and gper1 (very low expression) and was particularly high in the gonads at the female-producing temperature (FPT). After treatment with PPT, the MPT gonads presented obviously feminized morphology and structure, with the germ cells exhibiting a female distribution pattern. Furthermore, the mRNA expression levels of the key genes (dmrt1, amh, and sox9) for male differentiation were down-regulated significantly, while those of the key genes (foxl2 and cyp19a1) for female differentiation were up-regulated observably. The fluorescent signals of Amh and Sox9 expression almost disappeared, while Foxl2 and Arom were activated to express abundantly, which fully demonstrated the sex reversal of the gonads from male to female (sex reversal rate: 70.27%). However, the MPT gonads treated with WAY 200070 and G-1 still differentiated into testes, and the expression patterns of the key genes and proteins were similar to those in male gonads. The above results demonstrate that activation of Esr1 alone can fully initiate the early female differentiation process of gonads, suggesting that estrogen may induce early ovarian differentiation via Esr1 in Trachemys scripta. The findings provide a basis for further revealing the mechanisms of estrogen regulation in sex determination and differentiation of turtles.

Common functional mechanisms underlying dynamic brain network changes across five general anesthetics: A rat fMRI study.

BACKGROUND: Reversible loss of consciousness is the primary therapeutic endpoint of general anesthesia; however, the drug-invariant mechanisms underlying anesthetic-induced unconsciousness are still unclear. This study aimed to investigate the static, dynamic, topological and organizational changes in functional brain network induced by five clinically-used general anesthetics in the rat brain. METHOD: Male Sprague-Dawley rats (n = 57) were randomly allocated to received propofol, isoflurane, ketamine, dexmedetomidine, or combined isoflurane plus dexmedetomidine anesthesia. Resting-state functional magnetic resonance images were acquired under general anesthesia and analyzed for changes in dynamic functional brain networks compared to the awake state. RESULTS: Different general anesthetics induced distinct patterns of functional connectivity inhibition within brain-wide networks, resulting in multi-level network reorganization primarily by impairing the functional connectivity of cortico-subcortical networks as well as by reducing information transmission capacity, intrinsic connectivity, and network architecture stability of subcortical regions. Conversely, functional connectivity and topological properties were preserved within cortico-cortical networks, albeit with fewer dynamic fluctuations under general anesthesia. CONCLUSIONS: Our findings highlighted the effects of different general anesthetics on functional brain network reorganization, which might shed light on the drug-invariant mechanism of anesthetic-induced unconsciousness.

The effect of post-labeling delay on cerebral blood flow is influenced by age and sex: a study based on arterial spin-labeling magnetic resonance imaging.

Background: Whether the effect of post-labeling delay (PLD) on cerebral blood flow (CBF) is influenced by age and sex in adults is unknown. In this study, we mainly aimed to explore the potential influence of age and sex on the effect of PLD on CBF. Methods: This prospective study enrolled 90 healthy adult volunteers (49.47±15.63 years of age; age range, 20-77 years; 47 female; 43 male). All participants underwent 3-dimensional (3D) pseudo-continuous arterial spin labeling (ASL) imaging with 3 different PLDs (1,525, 2,025, and 2,525 ms). The CBF values for each PLD, the arterial transit time (ATT), and the spatial coefficient of variation (spatial CoV) were computed for 21 regions of interest (ROIs) in every participant. Multivariate regression analysis was conducted to assess the potential influence of age and sex on the effect of PLD on CBF and the relationships among CBF, ATT, PLD, age, sex, and spatial CoV. Results: The CBF increased for 7.32 to 9.87 mL/100 g/min as the PLD increased per 1 second in the global gray matter, bilateral frontal, temporal lobes, the vascular territories of bilateral anterior and middle carotid artery. When the age increased per 1 year, the speed of the changes for CBF decreased for 0.26 to 0.3 mL/100 g/min/s in these regions. However, the CBF decreased for 12 to 17 mL/100 g/min as the PLD increased per 1 second in the bilateral limbic lobes, insula, and deep gray matter. In these regions, the speed of the changes for CBF increased for 0.2 to 0.28 mL/100 g/min/s as the age increased per 1 year. Furthermore, compared to the female, the speed of the changes for CBF decreased for 3.58 to 4.6 mL/100 g/min/s for the male in global gray matter, bilateral frontal, limbic lobes, and the vascular territories of bilateral anterior carotid artery, and the speed increased 4.49 to 5.09 mL/100 g/min/s for the male in the limbic lobes. In addition, the CBF decreased with aging and the CBF tended to be higher in females compared to males. At the same time, we found that the ATT of all ROIs increased with age and manifested higher in males than females. Moreover, we found that CBF decreased with the increase of ATT, and the effect of ATT on CBF was less influenced by PLD. Finally, we found that the spatial CoV of ASL in certain regions increased with the increase of ATT and age, and was greater in males. Conclusions: The effect of PLD on CBF can be influenced by age and sex. The relationships among CBF, ATT, PLD, age, sex, and spatial CoV found in this study may have certain significance for the study of ASL imaging in the future.

Long-term impact of nusinersen on motor and electrophysiological outcomes in adolescent and adult spinal muscular atrophy: insights from a multicenter retrospective study.

BACKGROUND: 5q spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease. OBJECTIVE: We aimed to assess the effects of nusinersen on motor function and electrophysiological parameters in adolescent and adult patients with 5q SMA. METHODS: Patients with genetically confirmed 5q SMA were eligible for inclusion, and clinical data were collected at baseline (V1), 63 days (V4), 180 days (V5), and 300 days (V6). The efficacy of nusinersen was monitored by encompassing clinical assessments, including the Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 6-Minute Walk Test (6MWT), and percent-predicted Forced Vital Capacity in sitting position (FVC%) and Compound Muscle Action Potential (CMAP) amplitude. The patients were divided into "sitter" and "walker" subgroups according to motor function status. RESULTS: 54 patients were screened, divided into "sitter" (N = 22) and "walker" (N = 32), with the mean age at baseline of 27.03 years (range 13-53 years). The HFMSE in the walker subgroup increased significantly from baseline to V4 (mean change +2.32-point, P = 0.004), V5 (+3.09, P = 0.004) and V6 (+4.21, P = 0.005). The patients in both the sitter and walker subgroup had no significant changes in mean RULM between V1 and the following time points. Significant increases in CMAP amplitudes were observed in both upper and lower limbs after treatment. Also, patients with RULM ≥ 36 points showed significant CMAP improvements. Our analysis predicted that patients with CMAP amplitudes of trapezius ≥ 1.76 mV were more likely to achieve significant motor function improvements. CONCLUSIONS: Nusinersen effectively improves motor function and electrophysiological data in adolescent and adult patients with SMA. This is the first report on the CMAP amplitude changes in the trapezius after treatment in patients with SMA. The CMAP values effectively compensate for the ceiling effect observed in the RULM, suggesting that CMAP could serve as an additional biomarker for evaluating treatment efficacy.

Molecular Interaction Mechanisms Between Lubricant-Infused Slippery Surfaces and Mussel-Inspired Polydopamine Adhesive and DOPA Moiety.

Lubricant-infused slippery surfaces have recently emerged as promising antifouling coatings, showing potential against proteins, cells, and marine mussels. However, a comprehensive understanding of the molecular binding behaviors and interaction strength of foulants to these surfaces is lacking. In this work, mussel-inspired chemistry based on catechol-containing chemicals including 3,4-dihydroxyphenylalanine (DOPA) and polydopamine (PDA) is employed to investigate the antifouling performance and repellence mechanisms of fluorinated-based slippery surface, and the correlated interaction mechanisms are probed using atomic force microscopy (AFM). Intermolecular force measurements and deposition experiments between PDA and the surface reveal the ability of lubricant film to inhibit the contact of PDA particles with the substrate. Moreover, the binding mechanisms and bond dissociation energy between a single DOPA moiety and the lubricant-infused slippery surface are quantitatively investigated employing single-molecule force spectroscopy based on AFM (SM-AFM), which reveal that the infused lubricant layer can remarkably influence the dissociation forces and weaken the binding strength between DOPA and underneath per-fluorinated monolayer surface. This work provides new nanomechanical insights into the fundamental antifouling mechanisms of the lubricant-infused slippery surfaces against mussel-derived adhesive chemicals, with important implications for the design of lubricant-infused materials and other novel antifouling platforms for various bioengineering and engineering applications.