Facile Synthesis of Rigid Binuclear Manganese Complexes for Magnetic Resonance Angiography and SLC39A14-Mediated Hepatic Imaging.

Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.

Advances in the Removal of Organic Pollutants from Water by Photocatalytic Activation of Persulfate: Photocatalyst Modification Strategy and Reaction Mechanism.

Environmental pollution caused by persistent organic pollutants has imposed big threats to the health of human and ecological systems. The development of efficient methods to effectively degrade and remove these persistent organic pollutants is therefore of paramount importance. Photocatalytic persulfate-based advanced oxidation technologies (PS-AOTs), which depend on the highly reactive SO4·- radicals generated by the activation of PS to degrade persistent organic pollutants, have shown great promise. This work discusses the application and modification strategies of common photocatalysts in photocatalytic PS-AOTs, and compares the degradation performance of different catalysts for pollutants. Furthermore, essential elements impacting photocatalytic PS-AOTs are discussed, including the water matrix, reaction process mechanism, pollutant degradation pathway, singlet oxygen generation, and potential PS hazards. Finally, the existing issues and future challenges of photocatalytic PS-AOTs are summarized and prospected to encourage their practical application. In particular, by providing new insights into the PS-AOTs, this review sheds light on the opportunities and challenges for the development of photocatalysts with advanced features for the PS-AOTs, which will be of great interests to promote better fundamental understanding of the PS-AOTs and their practical applications.

The CfKOB1 gene related to cell apoptosis is required for pathogenicity and involved in mycovirus-induced hypovirulence in Colletotrichum fructicola.

Colletotrichum fructicola is a globally significant phytopathogenic fungus. Mycovirus-induced hypovirulence has great potential for biological control and study of fungal pathogenic mechanisms. We previously reported that the mycovirus Colletotrichum alienum partitivirus 1 (CaPV1) is associated with the hypovirulence of C. fructicola, and the present study aimed to further investigate a host factor and its roles in mycovirus-induced hypovirulence. A gene named CfKOB1, which encodes putative protein homologous to the ß-subunit of voltage-gated potassium channels and aldo-keto reductase, is downregulated upon CaPV1 infection and significantly upregulated during the early infection phase of Nicotiana benthamiana by C. fructicola. Deleting the CfKOB1 gene resulted in diminished vegetative growth, decreased production of asexual spores, hindered appressorium formation, reduced virulence, and altered tolerance to abiotic stresses. Transcriptome analysis revealed that CfKOB1 regulates many metabolic pathways as well as the cell cycle and apoptosis. Furthermore, enhanced apoptosis was observed in the ΔCfKOB1 mutants. Viral RNA accumulation was significantly increased in the CfKOB1 deletion mutant. Additionally, our findings demonstrated that CaPV1 infection in the WT strain also induced cell apoptosis. Collectively, these results highlight the diverse biological roles of the CfKOB1 gene in the fungus C. fructicola, while it also participates in mycovirus-induced hypovirulence by regulating apoptosis.

Metal-organic framework-derived trimetallic particles encapsulated by ultrathin nitrogen-doped carbon nanosheets on a network of nitrogen-doped carbon nanotubes as bifunctional catalysts for rechargeable zinc-air batteries.

Economical oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts with high activity aimed at replacing precious metal catalysts for rechargeable zinc-air batteries (ZABs) must be developed. In this study, a multiple hierarchical-structural material is developed using a facile dielectric barrier discharge (DBD) plasma surface treatment, solvothermal reaction, and high-temperature carbonization strategy. This strategy allows for the construction of nanosheets using nitrogen-doped carbon (NC) material-encapsulated ternary CoNiFe alloy nanoparticles (NPs) on a network of NC nanotubes (NCNTs), denoted as CoNiFe-NC@p-NCNTs. Precisely, the presence of abundant CoNiFe alloy NPs and the formation of M-N-C active sites created by transition metals (cobalt, nickel, and iron) coupled with NC can provide superior OER/ORR bifunctional properties. Moreover, the prepared NC layers with a multilevel pore structure contribute to a larger specific surface area, exposing numerous active sites and enhancing the uniformity of electron and mass movement. The CoNiFe0.08-NC@p-NCNTs show remarkable dual functionality for electrochemical oxygen reactions (ORR half-wave potential of 0.811 V, limiting current density of 5.73 mA cm-2 measured with a rotating disk electrode at a rotation speed of 1600 rpm, and OER overpotential of 351 mV at 10 mA cm-2), which demonstrates similar ORR performance to 20 wt% Pt/C and better OER performance than the commercial RuO2. A liquid ZAB prepared using the proposed material has excellent bifunctionality with an open-circuit voltage of 1.450 V and long-term cycling stability of 230 h@10 mA cm-2.

The cardiovascular system at high altitude: A bibliometric and visualization analysis.

BACKGROUND: When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM: To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS: The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS: A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION: Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.

Non-alcoholic fatty liver disease and sleep disorders.

Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.

Unsupervised OCT image despeckling with ground-truth- and repeated-scanning-free features.

Optical coherence tomography (OCT) can resolve biological three-dimensional tissue structures, but it is inevitably plagued by speckle noise that degrades image quality and obscures biological structure. Recently unsupervised deep learning methods are becoming more popular in OCT despeckling but they still have to use unpaired noisy-clean images or paired noisy-noisy images. To address the above problem, we propose what we believe to be a novel unsupervised deep learning method for OCT despeckling, termed Double-free Net, which eliminates the need for ground truth data and repeated scanning by sub-sampling noisy images and synthesizing noisier images. In comparison to existing unsupervised methods, Double-free Net obtains superior denoising performance when trained on datasets comprising retinal and human tissue images without clean images. The efficacy of Double-free Net in denoising holds significant promise for diagnostic applications in retinal pathologies and enhances the accuracy of retinal layer segmentation. Results demonstrate that Double-free Net outperforms state-of-the-art methods and exhibits strong convenience and adaptability across different OCT images.

Fixed-time synchronization for two-dimensional coupled reaction-diffusion complex networks: Boundary conditions analysis.

This paper examines fixed-time synchronization (FxTS) for two-dimensional coupled reaction-diffusion complex networks (CRDCNs) with impulses and delay. Utilizing the Lyapunov method, a FxTS criterion is established for impulsive delayed CRDCNs. Herein, impulses encompass both synchronizing and desynchronizing variants. Subsequently, by employing a Lyapunov-Krasovskii functional, two FxTS boundary controllers are formulated for CRDCNs with Neumann and mixed boundary condition, respectively. It is observed that vanishing Dirichlet boundary contributes to the synchronization of the CRDCNs. Furthermore, this study calculates the optimal constant for the Poincaré inequality in the square domain, which is instrumental in analyzing FxTS conditions for boundary controllers. Conclusive numerical examples underscore the efficacy of the proposed theoretical findings.

Evaluation of pharmacist-led medication reconciliation at county hospitals in China: A multicentre, open-label, assessor-blinded, nonrandomised controlled study.

Background: Due to a lack of related research, we aimed to determine the effectiveness of a pharmacist-led medication reconciliation intervention in China. Methods: We conducted a multicentre, prospective, open-label, assessor-blinded, cluster, nonrandomised controlled study at six county-level hospitals, with hospital wards serving as the clusters. We included patients discharged from the sampled hospitals who were aged ≥60 years; had ≥1 studied diagnoses; and were prescribed with ≥3 medications at discharge. Patients in the intervention group received a pharmacist-led medication reconciliation intervention and those in the control group received standard care. We assessed the incidence of medication discrepancies at discharge, patients' medication adherence, and health care utilisation within 30 days after discharge. Results: There were 429 patients in the intervention group (mean age = 72.5 years, standard deviation (SD) = 7.0) and 526 patients in the control group (mean age = 73.6 years, SD = 7.1). Of the 1632 medication discrepancies identified at discharge, fewer occurred in the intervention group (1.9 per patient on average) than the control group (2.6 per patient on average).The intervention significantly reduced the incidence of medication discrepancy by 9.6% (95% confidence interval (CI) = -15.6, -3.6, P = 0.002) and improved patients' medication adherence, with an absolute decrease in the mean adherence score of 2.5 (95% CI = -2.8, -2.2, P < 0.001). There was no significant difference in readmission rates between the intervention and control groups. Conclusions: Pharmacist-led medication reconciliation at discharge from Chinese county-level hospitals reduced medication discrepancies and improved patients' adherence among patients aged 60 years or above, though no impact on readmission after discharge was observed. Registration: ChiCTR2100045668.

Novel mutation leading to splice donor loss in a conserved site of DMD gene causes Duchenne muscular dystrophy with cryptorchidism.

BACKGROUND: As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. METHODS: In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype. RESULTS: In 30 of 115 patients (26.1%), we identified four novel genes (ARSH, DMD, MAGEA4 and SHROOM2) affecting at least five unrelated patients and four known genes (USP9Y, UBA1, BCORL1 and KDM6A) with the candidate rare pathogenic variants affecting at least two cases. Burden tests of rare variants revealed the genome-wide significances for newly identified genes (p<2.5×10-6) under the Bonferroni correction. Surprisingly, novel and known genes were mainly found on X chromosome (seven on X and one on Y) and all rare X-chromosomal segregating variants exhibited a maternal inheritance rather than de novo origin. CRISPR-Cas9 mouse modelling of a splice donor loss variant in DMD (NC_000023.11:g.32454661C>G), which resides in a conserved site across vertebrates, replicated bilateral cryptorchidism phenotypes, confirmed by MRI at 4 and 10 weeks. The movement tests further revealed symptoms of Duchenne muscular dystrophy (DMD) in transgenic mice. CONCLUSION: Our results revealed the role of the DMD gene mutation in causing cryptorchidism. The results also suggest that maternal-X inheritance of pathogenic defects could have a predominant role in the development of cryptorchidism.

Clinical evaluation of droplet digital pcr for suspected ascites infection in patients with liver cirrhosis.

BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.

Association between metabolic syndrome severity score and cardiovascular disease: results from a longitudinal cohort study on Chinese adults.

Objective: This study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults. Methods: 13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021. A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression. Results: Both the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380-2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329-2.470), 1.746 (1.265-2.410), and 2.817 (2.015-3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk (P for non-linearity = 0.437). Similar results were found in various sensitivity analyses. Conclusion: The MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.

Factors Associated with Family Functioning During Pregnancy by Adolescent and Young Adult Women.

Introduction: Pregnancy represents a stressful period for both women and their families. Whether the family maintains functioning during pregnancy could have significant implications on maternal and child health. In this study, we explored individual- and family-level factors associated with family functioning in adolescent and young adult mothers. Methods: This study was a secondary analysis of 295 young mothers, ages between 15 and 21 years. Multivariate logistic regression models were conducted to estimate adjusted odds ratios of exploratory factors on the risk of being in high family functioning group. The parent study was approved by the Institutional Review Boards at Yale University. Results: The mean score of family functioning was 5.14 out of 7. With the inclusion of individual-level factors (Model 1), significant associations were observed between high family functioning and having ever attended religious services (OR = 2.22, 95% CI: 1.20-4.09), low perceived discrimination (OR = 3.04, 95% CI: 1.60-5.75), and high perceived social support (OR = 3.74, 95% CI: 2.01-6.95). After including both individual- and family-level factors (Model 2), results identified significant associations between high family functioning and annual household income>$15,000 (OR = 9.82, 95% CI: 1.67-57.67, p = 0.011) and no experience of violence from any family members (OR = 4.94, 95% CI: 1.50-16.21, p = 0.008). Discussion: The models of care should be structured to support the continuity of maternity care in which health care providers have the opportunity to discover and utilize each family's strengths to provide the optimal caring experience for young mothers and their families as a unit.

Effect of an Airbag-selective Portal Vein Blood Arrester on the Liver after Hepatectomy: A New Technique for Selective Clamping of the Portal Vein.

OBJECTIVE: A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions. METHODS: Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels. RESULTS: Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group. CONCLUSION: Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy.

A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.

Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

Action Speaks Louder: The Role of Proactive Behavior between Creative Leadership and Employees' Creativity.

Drawing on social learning theory, this study presents a moderated mediation model to examine the role of proactive behavior and conformity value in the positive relationship between creative leadership and employees' creativity. Two-wave data are collected from 230 employees and their leaders in an automobile manufacturing enterprise in China, in which employees are encouraged to be creative because they need to implement novel designs and proposals to attract consumers. Statistical analysis reveals that proactive behavior partially mediates the influence of creative leadership on employees' creativity. Conformity value moderates not only the relationship between creative leadership and proactive behavior but also the indirect effect of creative leadership on employees' creativity via proactive behavior. The relationship and the mediating mechanism are stronger in the presence of employees' higher conformity value. We discuss the theoretical and practical implications as well as future research directions of the findings.

MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases.

Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven to be an effective local treatment modality but incompetent against metastases. Hence, the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a magnetic resonance imaging (MRI)-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with a programmed cell death 1 (PD-1) inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser. In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32°C to 60.7°C in 5 min. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided PTT/PDT results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.

Attitudes Toward the Uptake of Combination HIV Prevention Methods Among Young Black and Latino Heterosexual Couples Living in New York City: A Qualitative Study.

ABSTRACT: Couple-based HIV interventions that increase uptake of two or more effective biomedical HIV prevention methods may be a promising HIV prevention strategy for young Black and Latino heterosexual couples. We conducted in-depth, semi-structured individual interviews with 23 Black and Latino adolescent and young adult heterosexual couples that explored their attitudes toward using combination HIV prevention methods (CHPMs). A qualitative hybrid thematic analysis approach was used to identify key themes. Themes included: (a) attitudes that encouraged uptake-CHPMs increased assurance of safety against HIV/sexually transmitted infections and (b) attitudes that impeded uptake-CHPMs are too much to do and are not appropriate for serious relationships. Although Black and Latino adolescents and young adults may recognize the combined protective benefits of using multiple HIV prevention methods, personal and relational considerations play an instrumental role in uptake of CHPMs.

PCDHA9 as a candidate gene for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.

Cellulose Nanostructures as Tunable Substrates for Nanocellulose-Metal Hybrid Flexible Composites.

Nanocomposite represents the backbone of many industrial fabrication applications and exerts a substantial social impact. Among these composites, metal nanostructures are often employed as the active constituents, thanks to their various chemical and physical properties, which offer the ability to tune the application scenarios in thermal management, energy storage, and biostable materials, respectively. Nanocellulose, as an emerging polymer substrate, possesses unique properties of abundance, mechanical flexibility, environmental friendliness, and biocompatibility. Based on the combination of flexible nanocellulose with specific metal fillers, the essential parameters involving mechanical strength, flexibility, anisotropic thermal resistance, and conductivity can be enhanced. Nowadays, the approach has found extensive applications in thermal management, energy storage, biostable electronic materials, and piezoelectric devices. Therefore, it is essential to thoroughly correlate cellulose nanocomposites' properties with different metallic fillers. This review summarizes the extraction of nanocellulose and preparation of metal modified cellulose nanocomposites, including their wide and particular applications in modern advanced devices. Moreover, we also discuss the challenges in the synthesis, the emerging designs, and unique structures, promising directions for future research. We wish this review can give a valuable overview of the unique combination and inspire the research directions of the multifunctional nanocomposites using proper cellulose and metallic fillers.