Search

Organic synthesis often requires multiple steps where a functional group (FG) is concealed from reaction by a protecting group (PG). Common PGs include N -carbobenzyloxy (Cbz or Z) of amines and tert -butyloxycarbonyl (O t Bu) of acids. An essential step is the removal of the PG, but this often requires excess reagents, extensive time and can have low % yield. An overarching goal of biocatalysis is to use "green" or "enzymatic" methods to catalyse chemical transformations. One under-utilised approach is the use of "deprotectase" biocatalysts to selectively remove PGs from various organic substrates. The advantage of this methodology is the exquisite selectivity of the biocatalyst to only act on its target, leaving other FGs and PGs untouched. A number of deprotectase biocatalysts have been reported but they are not commonly used in mainstream synthetic routes. This study describes the construction of a cascade to deprotect doubly-protected amino acids. The well known Bacillus BS2 esterase was used to remove the O t Bu PG from various amino acid substrates. The more obscure Sphingomonas Cbz-ase (amidohydrolase) was screened with a range of N -Cbz-modified amino acid substrates. We then combined both the BS2 and Cbz-ase together for a 1 pot, 2 step deprotection of the model substrate CBz-L-Phe O t Bu to produce the free L-Phe. We also provide some insight into the residues involved in substrate recognition and catalysis using docked ligands in the crystal structure of BS2. Similarly, a structural model of the Cbz-ase identifies a potential di-metal binding site and reveals conserved active site residues. This new biocatalytic cascade should be further explored for its application in chemical synthesis.

Interruptions in the working environment cause extra mental workload for the operators, and this phenomenon has garnered significant research attention. This study designed four interruption conditions based on the perceptual and cognitive perspectives of human information processing, using a 2(perceptual primary task and cognitive primary task)*2(perceptual interruption task and cognitive interruption task) factorial design. Multimodal measurement methods were used to evaluate mental workload in different interruption conditions. The results show that when the primary task and the interruption task are different load types, they generate a higher mental workload than the same load type. It can be attributed to the fact that perceptual tasks and cognitive tasks increase mental workload during switching. In addition, based on the multimodal index data, the prediction model of interruption recovery delay time and the classification model of interruption conditions are established, which provides a basis for rational scheduling of work and preventing mental overload.

With the continuous advancement of nanotechnology, the application of gold nanorods (AuNRs) functionalized with polysaccharides in the realm of cancer photothermal therapy is garnering increasing attention. To harness photothermal therapy for cancer treatment, FLP-MPBA-AuNRs were successfully synthesized in this study for the first time, utilizing Poria cocos polysaccharides (FLP), mercaptophenylboronic acid (MPBA), and gold nanorods (AuNRs). FLP-MPBA-AuNRs is a nanomaterial characterized by a unique rod-shaped structure, featuring a long diameter of 29.3 nm and a short diameter of 6.5 nm, which conferred upon it exceptional photothermal stability and remarkable photothermal conversion efficiency. Under near-infrared light irradiation, FLP-MPBA-AuNRs elicited significant photothermal effects, effectively curtailing the proliferation of various cancer cells. Additionally, it impeded cancer progression by inducing cell apoptosis and releasing reactive oxygen species (ROS). Furthermore, FLP-MPBA-AuNRs suppressed the metastasis and growth of cancer cells in zebrafish models. In summary, FLP-MPBA-AuNRs showcased immense potential in cancer therapy by inhibiting tumor cell growth through photothermal and photodynamic mechanisms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Nucleic acid therapy is currently the most promising method for treating tumors and genetic diseases and for preventing infectious diseases. However, the biggest obstacle to this therapy is delivery of the nucleic acids to the target site, which requires overcoming problems such as capture by the immune system, the need to penetrate biofilms, and degradation of nucleic acid performance. Designing suitable delivery vectors is key to solving these problems. Lipids-which consist of a hydrophilic headgroup, a linker, and a hydrophobic tail-are crucial components for the construction of vectors. The headgroup is particularly important because it affects the drug encapsulation rate, the vector cytotoxicity, and the transfection efficiency. Herein, we focus on various headgroup structures (tertiary amines, quaternary ammonium salts, peptides, piperazines, dendrimers, and several others), and we summarize and classify important lipid-based carriers that have been developed in recent years. We also discuss applications of cationic lipids with various headgroups for delivery of nucleic acid drugs, and we analyze how headgroup structure affects transport efficiency and carrier toxicity. Finally, we briefly describe the challenges of developing novel lipid carriers, as well as their prospects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. Wanting Ma drafted the manuscript. Xingxing Fu and Tianyi Zhao searched part of the literature. Wanting Ma, Yinan Zhao, Yanfei Qi and Shubiao Zhang conceived and designed the work. Yinan Zhao, Yanfei Qi and Shubiao Zhang edited and revised the manuscript. All the authors have read and approved the final manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Background: Web- and mobile-based physical activity interventions effectively promote physical and mental health among older adults, but participation and adherence are suboptimal., Methods: This qualitative review used the mega-aggregation approach. Searches were conducted in five databases from the earliest to November 2023. Quality assessment and data extraction used JBI tools. Data synthesis used the COM-B model as a guide., Results: Sixteen sub-themes were identified from the eight studies and categorized into the COM-B model. Sub‑themes were physical and psychological changes, digital skills and knowledge, older adult-friendly design, integration into daily routines, social influence, family engagement and support, health benefits and impairments, accessibility and flexibility, low cost, visibility and interaction, instructions and feedback, personalization and progression, incentives, self-efficacy, visual cues, self-monitoring., Discussion: Web- and mobile-based interventions motivate older adults to engage in physical activity, but modifications are necessary. This includes age-appropriate interfaces and contents, tailored behavioral change techniques, and family engagement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Astrocytes and microglia undergo dynamic and complex morphological and functional changes following ischemic stroke, which are instrumental in both inflammatory responses and neural repair. While gene expression alterations poststroke have been extensively studied, investigations into posttranscriptional regulatory mechanisms, specifically alternative splicing (AS), remain limited. Utilizing previously reported Ribo-Tag-seq data, this study analyzed AS alterations in poststroke astrocytes and microglia from young adult male and female mice. Our findings reveal that in astrocytes, compared to the sham group, 109 differential alternative splicing (DAS) events were observed at 4 h poststroke, which increased to 320 at day 3. In microglia, these numbers were 316 and 266, respectively. Interestingly, the disparity between DAS genes and differentially expressed genes is substantial, with fewer than 10 genes shared at both poststroke time points in astrocytes and microglia. Gene ontology enrichment analysis revealed the involvement of these DAS genes in diverse functions, encompassing immune response (Adam8, Ccr1), metabolism (Acsl6, Pcyt2, Myo5a), and developmental cell growth (App), among others. Selective DAS events were further validated by semiquantitative RT-PCR. Overall, this study comprehensively describes the AS alterations in astrocytes and microglia during the hyperacute and acute phases of ischemic stroke and underscores the significance of certain hub DAS events in neuroinflammatory processes., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

This study investigates the relationship between self-rated health, social participation, spouse health, and depressive symptoms in older adults. It also analyzed the moderating effects of gender, drinking, visual function, diet, quality of life, and economic level on the model. We analyzed data from 5119 participants aged 60 and above, from the CLHLS. We used a partial least squares structural equation model to explore the correlation between self-rated health, spouse health, social participation, and depressive symptoms. Self-rated health was significantly correlated with spouse health, social participation, and depressive symptoms (P < 0.001). Social participation (β=-0.034) and spouse health (β=-0.029) were mediators of self-rated health to depressive symptoms. In addition, gender, drinking, visual function, diet, quality of life, and economic level were mediated factors. This study provides evidence that self-rated health has direct or indirect associations with depressive symptoms in older people, with social participation and spouse health playing a crucial mediating role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Depression is a common and complex mental illness that manifests as persistent episodes of sadness, loss of interest, and decreased energy, which might lead to self-harm and suicide in severe cases. Reportedly, depression affects 3.8 % of the world's population and has been listed as one of the major global public health concerns. In recent years, aromatherapy has been widely used as an alternative and complementary therapy in the prevention and treatment of depression; people can relieve anxiety and depression by sniffing plant aromatic essential oils. Acorus tatarinowii and Panax ginseng essential oils in Chang Shen Hua volatile oil (CSHVO) are derived from Acorus tatarinowii and Panax ginseng, respectively, the main medicines in the famous Chinese medicine prescription Kai Xin San (KXS), Then, these oils are combined with the essential oil of Albizia julibrissin flower to form a new Chinese medicine inhalation preparation, CSHVO. KXS has been widely used in the treatment of depression; however, whether CSHVO can ameliorate depression-like behavior, its pharmacological effects, and the underlying mechanisms of action are yet to be elucidated., Study Design and Methods: A rat model of chronic and unpredictable mild stimulation (CUMS) combined with orphan rearing was treated with CSHVO for 4 weeks. Using behavioral tests (sucrose preference, force swimming, tail suspension, and open field), the depression-like degree was evaluated. Concurrently, brain homogenate and serum biochemistry were analyzed to assess the changes in the neurotransmitters and inflammatory and neurotrophic factors. Furthermore, tissue samples were collected for histological and protein analyses. In addition, network pharmacology and molecular docking analyses of the major active compounds, potential therapeutic targets, and intervention pathways predicted a role of CSHVO in depression relief. Subsequently, these predictions were confirmed by in vitro experiments using a corticosterone (CORT)-induced PC12 cell damage model., Results: CSHVO inhalation can effectively improve the weight and depression-like behavior of depressed rats and regulate the expression of inflammatory factors and neurotransmitters. Hematoxylin-eosin, Nissl, and immunofluorescence staining indicated that compared to the model group, the pathological damage to the brain tissues of rats in the CSHVO groups was improved. The network pharmacological analysis revealed that 144 CSHVO active compounds mediate 71 targets relevant to depression treatment, most of which are rich in the cAMP signaling and inflammatory cytokine pathways. Protein-protein interaction analysis showed that TNF, IL6, and AKT are the core anti-depressive targets of CSHVO. Molecular docking analysis showed an adequate binding between the active ingredients and the key targets. In vitro experiments showed that compared to the model group, the survival rate of PC12 cells induced by CSHVO intervention was increased, the apoptosis rate was decreased, and the expression of inflammatory cytokines in the cell supernatant was improved. Western blot analysis and immunofluorescence staining confirmed that CSHVO regulates PC12 cells in the CORT model through the cAMP-PKA-CREB signaling pathway, and pretreatment with PKA blocker H89 eliminates the protective effect of CSHVO on CORT-induced PC12 cells., Conclusions: CSHVO improves CORT-induced injury in the PC12 cell model and CUMS combined with orphan rearing-induced depression model in rats. The antidepressant mechanism of CSHVO is associated with the modulation of the cAMP-PKA-CREB signaling pathway., Competing Interests: Declaration of competing interest The authors declare no competing interests associated with this study., (Copyright © 2024. Published by Elsevier GmbH.)

High-throughput sequencing and multiomics technologies have allowed increasing numbers of biomarkers to be mined and used for disease diagnosis, risk stratification, efficacy assessment, and prognosis prediction. However, the large number and complexity of tumor markers make screening them a substantial challenge. Machine learning (ML) offers new and effective ways to solve the screening problem. ML goes beyond mere data processing and is instrumental in recognizing intricate patterns within data. ML also has a crucial role in modeling dynamic changes associated with diseases. Used together, ML techniques have been included in automatic pipelines for tumor marker screening, thereby enhancing the efficiency and accuracy of the screening process. In this review, we discuss the general processes and common ML algorithms, and highlight recent applications of ML in tumor marker screening of genomic, transcriptomic, proteomic, and metabolomic data of patients with various types of cancers. Finally, the challenges and future prospects of the application of ML in tumor therapy are discussed., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. Xingxing Fu drafted the manuscript. Qi Zuo and Wanting Ma searched part of the literature. Xingxing Fu, Yinan Zhao, Yanfei Qi and Shubiao Zhang conceived and designed the work. Xingxing Fu, Yinan Zhao, Yanfei Qi and Shubiao Zhang edited and revised the manuscript. All the authors have read and approved the final manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Multiple sclerosis (MS) is the leading cause of neurologic disability in young adults, but the burden caused by MS in China is lacking. We aimed to comprehensively describe the prevalence and health loss due to MS by demographic and geographical variables from 1990 to 2019 across China., Methods: Data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). We used GBD methodology to systematically analyze the prevalence, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to MS by age, sex, and location from 1990 to 2019 in mainland China and its provinces. We also compared the MS burden in China with the world and other Group of 20 (G20) countries., Results: In 2019, 42,571 (95% uncertainty interval [UI] 33,001-53,329) individuals in China had MS, which doubled from 1990. The age-standardized prevalence rate of MS was 2.32 per 100,000 (95% UI 1.78-2.91), which increased by 23.31% (95% UI 20.50-25.89) from 1990, with most of the growth occurring after 2010. There was a positive latitudinal gradient with the increasing prevalence from south to north across China. The total DALYs caused by MS were 71,439 (95% UI 58,360-92,254) in 2019, ranking China third among G20 countries. Most of the MS burden in China derived from premature mortality, with the higher fraction of YLLs than that at the global level and most other G20 countries. From 1990 to 2019, the age-standardized DALY and YLL rate had nonsignificant changes; however, the age-standardized YLD rate substantially increased by 23.33% (95% UI 20.50-25.89). The geographic distribution of MS burden varied at the provincial level in China, with a slight downward trend in the age-standardized DALY rates along with increasing Socio-Demographic Index over the study period., Discussion: Although China has a low risk of MS, the substantial and increasing prevalent cases should not be underestimated. The high burden due to premature death and geographic disparity of MS burden reveals insufficient management of MS in China, highlighting the needs for increased awareness and effective intervention.

Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each., (© 2024. The Author(s).)

Aims: Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressing neurodegenerative disease caused by CSF1R gene mutations. This study aimed to identify and investigate the effect of a novel intronic mutation (c.1754-3C>G) of CSF1R on splicing., Methods: A novel intronic mutation was identified using whole-exome sequencing. To investigate the impact of this mutation, we employed various bioinformatics tools to analyze the transcription of the CSF1R gene and the three-dimensional structure of its encoded protein. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the findings., Results: A novel mutation (c.1754-3C>G) in CSF1R was identified, which results in exon 13 skipping due to the disruption of the 3' splice site consensus sequence NYAG/G. This exon skipping event was further validated in the peripheral blood of the mutation carrier through RT-PCR and Sanger sequencing. Protein structure prediction indicated a disruption in the tyrosine kinase domain, with the truncated protein showing significant structural alterations., Conclusions: Our findings underscore the importance of intronic mis-splicing mutations in the diagnosis and management of CSF1R-related leukoencephalopathy., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Maternal histone methyltransferase is critical for epigenetic regulation and development of mammalian embryos by regulating histone and DNA modifications. Here, we reported a novel mechanism by revealing the critical effects of maternal Ezh1/2 deletion on mitochondria in MII oocytes and early embryos in mice. We found that Ezh1/2 knockout in mouse MII oocytes impaired the structure of mitochondria and decreased its number, but membrane potential and respiratory function of mitochondrion were increased. The similar effects of Ezh1/2 deletion have been observed in 2-cell and morula embryos, indicating that the effects of maternal Ezh1/2 deficiency on mitochondrion extend to early embryos. However, the loss of maternal Ezh1/2 resulted in a severe defect of morula: the number, membrane potential, respiratory function, and ATP production of mitochondrion dropped significantly. Content of reactive oxygen species was raised in both MII oocytes and early embryos, suggesting maternal Ezh1/2 knockout induced oxidative stress. In addition, maternal Ezh1/2 ablation interfered the autophagy in morula and blastocyst embryos. Finally, maternal Ezh1/2 deletion led to cell apoptosis in blastocyst embryos in mice. By analyzing the gene expression profile, we revealed that maternal Ezh1/2 knockout affected the expression of mitochondrial related genes in MII oocytes and early embryos. The chromatin immunoprecipitation-polymerase chain reaction assay demonstrated that Ezh1/2 directly regulated the expression of genes Fxyd6, Adpgk, Aurkb, Zfp521, Ehd3, Sgms2, Pygl, Slc1a1, and Chst12 by H3K27me3 modification. In conclusion, our study revealed the critical effect of maternal Ezh1/2 on the structure and function of mitochondria in oocytes and early embryos, and suggested a novel mechanism underlying maternal epigenetic regulation on early embryonic development through the modulation of mitochondrial status., (© 2024 Wiley Periodicals LLC.)

Background: To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD., Methods: This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort., Results: The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort., Conclusions: Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Momordica charantia L. ( M. charantia ) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM., Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals., Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: -0.85 mmol/L; 95%CI: -1.44, -0.26; p  = 0.005; I 2  = 73.4 %), postprandial glucose (PPG) (WMD: -2.28 mmol/L; 95%CI: -3.35, -1.21; p  = 0.000; I 2  = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.38 %; 95%CI: -0.53, -0.23; p  = 0.000; I 2  = 37.6 %), and total cholesterol (TC) (WMD: -0.38 mmol/L; 95%CI: -0.70, -0.07; p  = 0.017; I 2  = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)., Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

An undisclosed polysaccharide, BCP80-2, was isolated from Belamcanda chinensis (L.) DC. Structural investigation revealed that BCP80-2 consists of ten monosaccharide residues including t-α-Araf-(1→, →3,5)-α-Araf-(1→, →5)-α-Araf-(1→, →4)-β-Xylp-(1→, →3)-α-Rhap-(1→, →4)-β-Manp-(1→, t-β-Glcp-(1→, →6)-α-Glcp-(1→, t-β-Galp-(1→, and→3)-α-Galp-(1→. In vivo activity assays showed that BCP80-2 significantly suppressed neoplasmic growth, metastasis, and angiogenesis in zebrafish. Mechanistic studies have shown that BCP80-2 inhibited cell migration of HepG2 cells by suppressing the FAK signaling pathway. Moreover, BCP80-2 also activated immunomodulation and upregulated the secretion of co-stimulatory molecules CD40, CD86, CD80, and MHC-II. In conclusion, BCP80-2 inhibited tumor progression by targeting the FAK signaling pathway and activating CD40-induced adaptive immunity., Competing Interests: Declaration of competing interest Each author has completed the corresponding work, and there is no conflict of interest between the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sucrose esters (SEs) have great potential in the field of nucleic acid delivery due to their unique physical and chemical properties and good biosafety. However, the mechanism of the effect of SEs structure on delivery efficiency has not been studied. The liposomes containing peptide lipids and SEs were constructed, and the effects of SEs on the interaction between the liposomes and DNA were studied. The addition of SEs affects the binding rate of liposomes to DNA, and the binding rate gradually decreases with the increase of SEs' carbon chain length. SEs also affect the binding site and affinity of liposomes to DNA, promoting the aggregation of lipids to form liposomes, where DNA wraps around or compresses inside the liposomes, allowing it to compress DNA without damaging the DNA structure. COL-6, which is composed of sucrose laurate, exhibits the optimal affinity for DNA, and SE promotes the formation of ordered membrane structure and enhances membrane stability, so that COL-6 exhibits a balance between rigidity and flexibility, and thus exhibits the highest delivery efficiency of DNA among these formulations. This work provides theoretical foundations for the application of SE in gene delivery and guides for the rational design of delivery systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon β was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country., (© The Author(s), 2024.)

In this paper, we propose and demonstrate enhanced orthogonal frequency division multiplexing with index modulation (OFDM-IM) schemes for bandlimited underwater visible light communication (UVLC) systems via geometric constellation shaping (GCS) and subblock interleaving. Specifically, two heuristic GCS approaches based on particle swarm optimization (PSO) and hybrid genetic algorithm-PSO (GA-PSO) algorithms are proposed to generate IM-preferable constellations. Moreover, a generalized interleaving technique is further proposed to overcome the low-pass effect of bandlimited UVLC systems, where an optimal step size can be obtained to perform subblock interleaving. Simulation and experiments are conducted to evaluate the performance of the proposed enhanced OFDM-IM schemes in bandlimited UVLC systems, where both OFDM with single-mode index modulation (OFDM-SM) and OFDM with dual-mode index modulation (OFDM-DM) schemes are considered. The experimental results demonstrate remarkable signal-to-noise ratio (SNR) gains of 1.3 and 1.9 dB for OFDM-SM and OFDM-DM in comparison to the benchmark schemes, respectively.

Background: Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years., Methods: This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan-Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms., Results: A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO 2 over 14 years was significantly associated with fewer depressive symptoms., Conclusions: In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution., (© 2024. The Author(s).)

Background: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG., Methods: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk., Results: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in T H 2 cells and MG risk., Conclusions: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development., (© 2024. The Author(s).)

Purpose: To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque., Patients and Methods: We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability., Results: Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P<0.05)., Conclusion: High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhao et al.)

Purpose: Perivascular epicardial fat stranding detected in the coronary computed tomography (CT) angiography is associated with culprit lesions and provides helpful information on the risk of acute coronary syndrome. This study aimed to evaluate the potential clinical significance of pericarotid fat stranding (PCFS) and investigate the association between PCFS and short-term prognosis in acute stroke using head and neck CT angiography (CTA)., Methods: This study included 80 patients (mean age, 69.69 ± 11.03; 58 men) who underwent both head and neck CTA and magnetic resonance imaging within a 1-week period. Baseline characteristics, pericarotid adipose tissue attenuation, plaque characteristics, ischemic penumbra, infarct core volume, infarct core growth rate (CGR), and the grade of collateral status were recorded and compared between a PCFS group and a non-PCFS group. Data were compared using the 2-sample t test, Mann-Whitney U test, Fisher exact test, and Spearman rank correlation analysis., Results: We found that patients with PCFS had a significantly higher pericarotid adipose tissue density than patients without PCFS (-55.75 ± 5.53 vs -65.82 ± 9.65, P < 0.001). Patients with PCFS showed a larger infarct core volume (166.43 ± 73.07 vs 91.43 ± 55.03, P = 0.001) and faster CGR (39.57 ± 12.01 vs 19.83 ± 32.77; P < 0.001), and the frequency of adverse prognosis was more significant than in control participants (83.33% vs 19.11%)., Conclusions: Individuals with PCFS showed higher CGR, which was substantially related to worse outcomes in patients with acute stroke with ipsilateral carotid atherosclerosis. Recognition of PCFS may help predict stroke prognosis and allow doctors to take early action to improve patient prognosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The study aimed to investigate the predictive value of clinical characteristics, major computed tomography angiography (CTA) indexes of carotid AS (carotid lumen stenosis and plaque burden), and inflammatory pericarotid adipose tissue for acute stroke risk in patients with a moderate or higher degree of carotid stenosis. In all, 119 patients with unilateral carotid stenosis who underwent head and neck computed tomography angiography were included and assigned to the stroke group or non-stroke group according to magnetic resonance imaging. Pericarotid adipose tissue attenuation value, net enhancement value in the base phase and the enhancement phase, and atherosclerotic features (plaque burden and lumen stenosis) were recorded. Multivariate logistic regression analysis and the operating characteristic curve (ROC) were performed to establish a predictive model for the presence of acute ischemic stroke. ROC analysis showed that pericarotid adipose tissue attenuation value and lumen stenosis were predictive factors for stroke. The AUC of pericarotid adipose tissue attenuation (PCAT) attenuation, lumen stenosis, the novel prediction model independently constructed based on PCAT attenuation, and lumen stenosis resulted in 0.838 (95% CI 0.759-0.899), 0.700 (95% CI 0.826-0.944), and 0.942 (95% CI 0.884-0.977), respectively. The model had a sensitivity and specificity of 0.909 and 0.893, respectively, when the cutoff value was 0.388. We found that the risk model combining pericarotid adipose tissue attenuation value and lumen stenosis has significant predictive values for the presence of symptomatic stroke among patients with a moderate or higher degree of carotid stenosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: To identify intrinsic capacity trajectories, predictors of intrinsic capacity trajectories and associations between intrinsic capacity trajectories and care dependence in community-dwelling older adults in China., Methods: A retrospective longitudinal study was conducted, and the data were obtained from a five-year national longitudinal cohort study of older adults in China between 2011 and 2015. The social determinants of health framework informed the data analysis and interpretation., Results: A total of 3893 older adults met the selection criteria and were included in the study. Three intrinsic capacity trajectories were identified: high trajectory (15.7 %), stable trajectory (52.7 %) and declining trajectory (31.6 %). Social determinants contribute to intrinsic capacity decline in older adults. Decreased cognitive function, psychological status, and locomotion at baseline were associated with care dependence., Conclusion: Approximately thirty percent of the older adults in this cohort study experienced a decline in intrinsic capacity within a 5-year period. Social determinants contributed to this decline in older adults., Competing Interests: Declaration of competing interest On behalf of all the authors, I declare that all authors have contributed to the work, we all agree with the findings presented, and that the work has not been published before nor is being considered for publication in another journal. There is no interest conflict in this study., (Copyright © 2023. Published by Elsevier Inc.)

Background: The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not., Methods: A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately., Results: After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model., Conclusion: The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion., (© 2023. The Author(s).)

In this Letter, we propose and demonstrate a dual-mode spatial index modulation (DM-SIM) scheme for spectral efficiency enhancement of band-limited multiple-input multiple-output optical wireless communication (MIMO-OWC) systems. By performing dual-mode index modulation in the spatial domain, DM-SIM can transmit both spatial and constellation symbols. Since constellation design plays a vital role in the proposed DM-SIM scheme, we further propose three dual-mode constellation design approaches including phase rotation, amplitude scaling and joint phase rotation and amplitude scaling. Moreover, we also designed a differential log-likelihood ratio (LLR) detector for the proposed DM-SIM scheme. Experimental results show that the joint phase rotation and amplitude scaling approach can achieve a remarkable 3.2 dB signal-to-noise ratio (SNR) gain compared with the phase rotation approach in a 2×2 MIMO-OWC system applying DM-SIM.

Background: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation., Methods: Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells., Results: SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner., Conclusions: This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC., (© 2024. The Author(s).)

In recent years, the application of nanoparticles formed by coupling metal nanomaterials of photothermal therapy with polysaccharides as modified carriers in the targeted treatment of liver cancer has attracted extensive attention. In the present work, an undescribed homogeneous polysaccharide BCP50-2 was obtained from Belamcanda chinensis (L.) DC. The structural analysis displayed that BCP50-2 contained galactose and a small amount of arabinose, and was mainly composed of six monosaccharide residues: →3,5)-α-l-Araf-(1→, →4)-β-d-Galp-(1→, →4,6)-β-d-Galp-(1→, →3)-α-l-Galp-(1→, terminal α-l-Araf, and terminal β-d-Galp. To enhance the antitumor activity of BCP50-2, BCP50-2-AuNRs were prepared by coupling BCP50-2 with gold nanorods for the treatment of liver cancer. BCP50-2-AuNRs were rod-shaped with a long diameter of 26.8 nm and had good photothermal conversion effects. Under near-infrared (NIR) light irradiation, BCP50-2-AuNRs possessed photothermal effects and suppressed the growth of HepG2, A549, and MCF-7 cells. In addition, BCP50-2-AuNRs inhibited the development of liver cancer by inducing cell apoptosis, arresting the cell cycle in G2/M phases, and inhibiting cell migration. Moreover, BCP50-2-AuNRs inhibited tumor proliferation, migration, and angiogenesis in zebrafish. In summary, BCP50-2-AuNRs may be potentially useful for cancer treatment., Competing Interests: Declaration of competing interest Each author has completed the corresponding work, and there is no conflict of interest between the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To solve error propagation and exorbitant computational complexity of signal detection in wireless multiple-input multiple-output-orthogonal frequency division multiplexing (MIMO-OFDM) systems, a low-complex and efficient signal detection with iterative feedback is proposed via a constellation point feedback optimization of minimum mean square error-ordered successive interference cancellation (MMSE-OSIC) to approach the optimal detection. The candidate vectors are formed by selecting the candidate constellation points. Additionally, the vector most approaching received signals is chosen by the maximum likelihood (ML) criterion in formed candidate vectors to reduce the error propagation by previous erroneous decision, thus improving the detection performance. Under a large number of matrix inversion operations in the above iterative MMSE process, effective and fast signal detection is hard to be achieved. Then, a symmetric successive relaxation iterative algorithm is proposed to avoid the complex matrix inversion calculation process. The relaxation factor and initial iteration value are reasonably configured with low computational complexity to achieve good detection close to that of the MMSE with fewer iterations. Simultaneously, the error diffusion and complexity accumulation caused by the successive detection of the subsequent OSIC scheme are also improved. In addition, a method via a parallel coarse and fine detection deals with several layers to both reduce iterations and improve performance. Therefore, the proposed scheme significantly promotes the MIMO-OFDM performance and thus plays an irreplaceable role in the future sixth generation (6G) mobile communications and wireless sensor networks, and so on.

Background: Middle-aged and older adults frequently experience hearing loss and a decline in cognitive function. Although an association between hearing difficulty and cognitive function has been demonstrated, its temporal sequence remains unclear. Therefore, we investigated whether there are bidirectional relationships between hearing difficulty and cognitive function and explored the mediating role of depressive symptoms in this relationship., Method: We used the cross-lagged panel model and the random-intercept cross-lagged panel model to look for any possible two-way link between self-reported hearing difficulty and cognitive function. To investigate depressive symptoms' role in this association, a mediation analysis was conducted. The sample was made up of 4,363 adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS; 2011-2018; 44.83% were women; mean age was 56.16 years). One question was used to determine whether someone had a hearing impairment. The tests of cognitive function included episodic memory and intelligence. The Center for Epidemiologic Studies Depression Scale, which consists of 10 items, was used to measure depressive symptoms., Results: A bidirectional association between hearing and cognition was observed, with cognition predominating (Wald χ 2 (1) = 7.241, p < 0.01). At the between-person level, after controlling for potential confounders, worse hearing in 2011 predicted worse cognitive function in 2013 ( β = -0.039, p < 0.01) and vice versa ( β = -0.041, p < 0.01) at the between-person level. Additionally, there was no corresponding cross-lagged effect of cognitive function on hearing difficulty; rather, the more hearing difficulty, the greater the cognitive decline at the within-person level. According to the cross-lagged mediation model, depressive symptoms partially mediates the impact of cognitive function on subsequent hearing difficulty (indirect effect: -0.003, bootstrap 95% confidence interval: -0.005, -0.001, p < 0.05), but not the other way around., Conclusion: These results showed that within-person relationships between hearing impairment and cognitive function were unidirectional, while between-person relationships were reciprocal. Setting mental health first may be able to break the vicious cycle that relates hearing loss to cognitive decline. Comprehensive long-term care requires services that address depressive symptoms and cognitive decline to be integrated with the hearing management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Hu, Zhao, Peng, Guo, Zhang, Huang, Feng and Sun.)

Multifunctional biomass-based aerogels with mechanically robust and high fire safety are urgently needed for the development of environmentally-friendly intelligent fire fighting but challenging. Herein, a novel polymethylsilsesquioxane (PMSQ)/cellulose/MXene composite aerogel (PCM) with superior comprehensive performance was fabricated by ice-induced assembly and in-situ mineralization. It exhibited light weight (16.2 mg·cm -3 ), excellent mechanical resilience, and rapidly recovered after being subjected to the pressure of 9000 times of its own weight. Moreover, PCM demonstrated outstanding thermal insulation, hydrophobicity and sensitive piezoresistive sensing. In addition, benefiting from the synergism of PMSQ and MXene, PCM displayed good flame retardancy and improved thermostability. The limiting oxygen index of PCM was higher than 45.0 %, and it quickly self-extinguished after being removed away from fire. More importantly, the rapid electrical resistance reduction of MXene at high temperature endowed PCM with sensitive fire-warning capability (trigger time was less than 1.8 s), which provided valuable time for people to evacuate and relief. This work provides new insights for the preparation and application of the next-generation high performance biomass-based aerogels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This paper proposes an improved frequency domain turbo equalization (IFDTE) with iterative channel estimation and feedback to achieve both a good performance and low complexity in underwater acoustic communications (UWACs). A selective zero-attracting (SZA) improved proportionate normal least mean square (SZA-IPNLMS) algorithm is adopted by utilizing the sparsity of the UWAC channel to estimate it using a training sequence. Simultaneously, a set-membership (SM) SZA differential IPNLMS (SM SZA-DIPNLMS) with variable step size is adopted to estimate the channel status information (CSI) in the iterative channel estimation with soft feedback. In this way, the computational complexity for iterative channel estimation is reduced effectively with minimal performance loss. Different from traditional schemes in UWACs, an IFDTE with expectation propagation (EP) interference cancellation is adopted to estimate the a posteriori probability of transmitted symbols iteratively. A bidirectional IFDTE with the EP interference cancellation is proposed to further accelerate the convergence. THe simulation results show that the proposed channel estimation obtains 1.9 and 0.5 dB performance gains, when compared with those of the IPNLMS and the l0-IPNLMS at a bit error rate (BER) of 10-3. The proposed channel estimation also effectively reduces the unnecessary updating of the coefficients of the UWAC channel. Compared with traditional time-domain turbo equalization and FDTE in UWACs, the IFDTE obtains 0.5 and 1 dB gains in the environment of SPACE'08 and it obtains 0.5 and 0.4 dB gains in the environment of MACE'04 at a BER of 10-3. Therefore, the proposed scheme obtains a good BER performance and low complexity and it is suitable for efficient use in UWACs.

Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo , with IC 50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Chen, Jin, Li, Zhu, Zhang, Zhi, Zhao, Li and Zhang.)

Nucleic acid-based therapies such as messenger RNA have the potential to revolutionize modern medicine and enhance the performance of existing pharmaceuticals. The key challenges of mRNA-based therapies are delivering the mRNA safely and effectively to the target tissues and cells and controlling its release from the delivery vehicle. Lipid nanoparticles (LNPs) have been widely studied as drug carriers and are considered to be state-of-the-art technology for nucleic acid delivery. In this review, we begin by presenting the advantages and mechanisms of action of mRNA therapeutics. Then we discuss the design of LNP platforms based on ionizable lipids and the applications of mRNA-LNP vaccines for prevention of infectious diseases and for treatment of cancer and various genetic diseases. Finally, we describe the challenges and future prospects of mRNA-LNP therapeutics., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. Zhe Wang drafted the manuscript. Wanting Ma and Xingxing Fu searched part of the literature. Zhe Wang, Yinan Zhao, Yanfei Qi and Shubiao Zhang conceived and designed the work. Yinan Zhao, Yanfei Qi and Shubiao Zhang edited and revised the manuscript. All the authors have read and approved the final manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Quercetin (QT) is a very effective anticancer drug in combating breast cancer. However, it has several disadvantages such as poor water solubility, low bioavailability and low targeting, which seriously restrict its clinical application. In this work, amphiphilic hyaluronic acid polymers (dHAD) were synthesized by grafting dodecylamine to hyaluronic acid (HA). The dHAD self-assembles with QT to form drug-carrying micelles (dHAD-QT). The dHAD-QT micelles possessed excellent drug-loading capacities (75.9 %) for QT and showed significantly improved CD44 targeting compared with unmodified HA. dHAD-QT micelles exhibited high cytotoxicity and apoptosis-inducing abilities, which were ascribed to the pH-sensitive dHAD-QT micelles accomplishing rapid drug release of QT under low pH condition. Importantly, in vivo experiments showed that dHAD-QT effectively inhibited tumor growth in tumor-bearing mice, with a tumor inhibition rate of 91.8 %. Furthermore, dHAD-QT prolonged the survival time of tumor-bearing mice and reduced the toxicity of the drug to normal tissues. These findings indicate that the designed dHAD-QT micelles have promising potential as efficient nano-drugs for breast cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competitive financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

China has made great progress in the electrification of passenger cars, and the sales of battery electric vehicles (BEVs) have exceeded 10%. We applied a life-cycle assessment (LCA) method to estimate the carbon dioxide (CO 2 ) emissions of the past (2015), present (2020), and future (2030) BEVs, incorporating China's carbon peaking and neutrality policies, which would substantially reduce emissions from the electricity, operation efficiency, metallurgy, and battery manufacturing industries. BEVs can reduce cradle-to-grave (C2G) CO 2 emissions by ∼40% compared with internal combustion engine vehicles (ICEVs) on the national-average level in 2020, far more significant than the benefit in 2015. Improved BEV operating efficiency was the largest factor driving emission reductions from 2015 to 2020. Looking forward to 2030, China's BEVs equipped with nickel-cobalt-manganese (NCM) batteries can achieve a further 43% of CO 2 emissions reductions, among which 51 g km -1 of reduction is from the well-to-wheels (WTW) stage majorly owing to the further cleaner electricity mix, while other vehicle-cycle benefits are mainly from the advancement of battery (12 g km -1 ) and related metal materials (5 g km -1 ). We highlight the importance of better material efficiency and synchronized decarbonization through the automotive industrial chain in promoting climate mitigation from transport activities., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: A hallmark signature of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) is abundantly infiltration of cancer-associated fibroblasts (CAFs), which facilitate HNSCC progression. However, some clinical trials showed targeted CAFs ended in failure, even accelerated cancer progression. Therefore, comprehensive exploration of CAFs should solve the shortcoming and facilitate the CAFs targeted therapies for HNSCC. Methods: In this study, we identified two CAFs gene expression patterns and performed the single-sample gene set enrichment analysis (ssGSEA) to quantify the expression and construct score system. We used multi-methods to reveal the potential mechanisms of CAFs carcinogenesis progression. Finally, we integrated 10 machine learning algorithms and 107 algorithm combinations to construct most accurate and stable risk model. The machine learning algorithms contained random survival forest (RSF), elastic network (Enet), Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox (plsRcox), supervised principal components (SuperPC), generalised boosted regression modelling (GBM), and survival support vector machine (survival-SVM). Results: There are two clusters present with distinct CAFs genes pattern. Compared to the low CafS group, the high CafS group was associated with significant immunosuppression, poor prognosis, and increased prospect of HPV negative. Patients with high CafS also underwent the abundant enrichment of carcinogenic signaling pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation. The MDK and NAMPT ligand-receptor cellular crosstalk between the cancer associated fibroblasts and other cell clusters may mechanistically cause immune escape. Moreover, the random survival forest prognostic model that was developed from 107 machine learning algorithm combinations could most accurately classify HNSCC patients. Conclusion: We revealed that CAFs would cause the activation of some carcinogenesis pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation and revealed unique possibilities to target glycolysis pathways to enhance CAFs targeted therapy. We developed an unprecedentedly stable and powerful risk score for assessing the prognosis. Our study contributes to the understanding of the CAFs microenvironment complexity in patients with head and neck squamous cell carcinoma and serves as a basis for future in-depth CAFs gene clinical exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zhao, Wang and Tan.)

Hospitalized patients who lose one or more activities of daily living at the time of discharge compared with 2 weeks before admission (before acute onset) are referred to as hospitalization-associated disability (HAD). The incidence of HAD is high among elderly patients, which leads to the increased readmission rates, long-term care rates, and mortality, bringing a huge burden on patients, families, and society. It is vital for doctors and nurses to identify the risk factors of HAD of the elderly patients and take targeted intervention measures to prevent and improve HAD. At present, the research on HAD in foreign countries is relatively perfect, while the research on HAD in China is still in its infancy, and there is still lack of systematic research and reports on the incidence, influencing factors, and intervention measures of HAD. Domestic clinical nursing practice can learn from foreign mature interventions, carry out cultural adjustment, create a friendly environment in the hospital for elderly patients, pay attention to the assessment of the influencing factors of HAD in elderly patients, and provide personalized and patient-centered nursing measures for hospitalized elderly patients according to the assessment results, maintain their function during hospitalization and prevent the occurrence of HAD.

Social participation is a key factor in achieving active aging. This study aimed to explore the trajectories and predictors of social participation changes among older adults in China. The data used in this study are from the ongoing national longitudinal study CLHLS. A total of 2492 older adults from the cohort study were included. Group-based trajectory models (GBTM) were used to identify potential heterogeneity in longitudinal changes over time and investigate associations between baseline predictors and trajectories for different cohort members using logistic regression. Four different trajectories of social participation were reported in older adults, namely, stable (8.9%), slow decline (15.7%), lower score with decline (42.2%), and higher score with decline (9.5%). On multivariate analyses, age, years of schooling, pension, mental health, cognitive function, instrumental activities of daily living, and initial social participation scores significantly impact the rate of change in social participation over time. Four trajectories of social participation were identified in the Chinese elderly population. Management of mental health, physical function, and cognitive function appear to be important in maintaining the long-term social participation of older people in the community. Early identification of factors influencing the rapid decline in social participation and timely interventions can maintain or improve social participation levels in older adults.

Background: We developed a novel system for quantifying DNA damage response (DDR) to help diagnose and predict the risk of Alzheimer's disease (AD)., Methods: We thoroughly estimated the DDR patterns in AD patients Using 179 DDR regulators. Single-cell techniques were conducted to validate the DDR levels and intercellular communications in cognitively impaired patients. The consensus clustering algorithm was utilized to group 167 AD patients into diverse subgroups after a WGCNA approach was employed to discover DDR-related lncRNAs. The distinctions between the categories in terms of clinical characteristics, DDR levels, biological behaviors, and immunological characteristics were evaluated. For the purpose of choosing distinctive lncRNAs associated with DDR, four machine learning algorithms, including LASSO, SVM-RFE, RF, and XGBoost, were utilized. A risk model was established based on the characteristic lncRNAs., Results: The progression of AD was highly correlated with DDR levels. Single-cell studies confirmed that DDR activity was lower in cognitively impaired patients and was mainly enriched in T cells and B cells. DDR-related lncRNAs were discovered based on gene expression, and two different heterogeneous subtypes (C1 and C2) were identified. DDR C1 belonged to the non-immune phenotype, while DDR C2 was regarded as the immune phenotype. Based on various machine learning techniques, four distinctive lncRNAs associated with DDR, including FBXO30-DT, TBX2-AS1, ADAMTS9-AS2, and MEG3 were discovered. The 4-lncRNA based riskScore demonstrated acceptable efficacy in the diagnosis of AD and offered significant clinical advantages to AD patients. The riskScore ultimately divided AD patients into low- and high-risk categories. In comparison to the low-risk group, high-risk patients showed lower DDR activity, accompanied by higher levels of immune infiltration and immunological score. The prospective medications for the treatment of AD patients with low and high risk also included arachidonyltrifluoromethane and TTNPB, respectively., Conclusions: In conclusion, immunological microenvironment and disease progression in AD patients were significantly predicted by DDR-associated genes and lncRNAs. A theoretical underpinning for the individualized treatment of AD patients was provided by the suggested genetic subtypes and risk model based on DDR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lai, Lin, Chen, Lin, Wu, Zhao, Lin and Lin.)

Background: Urinary incontinence is an increasingly common problem, especially among older people in nursing homes. Nursing assistants are the leading workforce in nursing homes, and their knowledge and attitudes regarding urinary incontinence have garnered considerable attention in the context of aging in China. However, most previous studies on this issue have focused on registered nurses. This study aimed to explore nursing assistants' knowledge, attitudes and training needs with regard to urinary incontinence., Methods: We conducted a two-part mixed-methods study. After institutional manager approval, we surveyed the knowledge and attitudes of 509 nursing assistants regarding urinary incontinence. We carried out semi-structured interviews with 40 nursing assistants to elicit detailed information on training needs., Results: In general, knowledge about urinary incontinence was poor (14.00 ± 4.18), although attitudes were primarily positive (35.51 ± 3.19). Most nursing assistants were very willing to learn more about urinary incontinence (93.9%, 478/509), but time constraints and low educational background may be barriers to learning motivation. The three preferred training styles among nursing assistants were face-to-face guidance from a mentor, training combining theory with practice, and online video training., Conclusions: Chinese nursing assistants had poor knowledge but positive attitudes toward urinary incontinence. Facility managers should focus on developing training and learning mechanisms regarding urinary incontinence. It is important to adopt diverse training styles according to the actual situation of nursing homes., (© 2023. The Author(s).)

Raman spectra of two series of InAs/AlAs short-period superlattices were measured at room temperature to investigate the impact of strain on the phonon modes taking into consideration the confinement effect and interface mode. The evolution of strain in the InAs layer and the AlAs layer was studied in (InAs) 2 /(AlAs) 2 superlattices grown at various temperatures (400-550 °C). While the strain existed in the AlAs layer remained almost constant, the strain in the InAs layer varied significantly as the growth temperature increased from 500 to 550 °C. The confinement effect on the optical phonons was analyzed based on results from (InAs) n /(AlAs) n grown at 450 °C (n = 2, 3, 4, and 5). Additionally, the confinement effect was found to be stronger in shorter periods with higher interface quality. The interface phonon modes were resolved between the longitudinal optical and transverse optical phonon modes, which assist in the rough estimation of the thickness of the layers. The disorder-activated acoustic phonon modes at the low-frequency side were also addressed., (© 2023. The Author(s).)

Photothermal therapy is a novel strategy for cancer treatment, which can kill tumor cells by converting light energy into heat energy through irradiating photothermal conversion materials with laser. As a common photothermal agent, gold nanorods (GNRs) have characteristics of high conversion efficiency and long circulation time in vivo. However, improving stability and reducing toxicity of GNRs remain a significant challenge. In this research, a simple and novel strategy for the synthesis of modified GNRs was proposed. The polysaccharide CL90 was obtained from lemon, which was modified to afford thiolated lemon polysaccharide (SH-CL90). SH-CL90 was used to prepare stable GNRs and give the composite GNRs-SH-CL90, which was found to have good stability in PBS solution and possess high photothermal conversion effects and photothermal stability. The biological experiments revealed that GNRs-SH-CL90 inhibited tumor cell proliferation under near-infrared light irradiation and could induce apoptosis significantly. Furthermore, in vivo experiments supported that GNRs-SH-CL90 could inhibit the proliferation and migration of tumor cells. All the experiments demonstrated that GNRs-SH-CL90 might be promising in the field of cancer treatment., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Immune-checkpoint blockade (ICB) has been routinely implemented to treat head and neck squamous cell carcinoma (HNSCC) patients. However, only a few patients benefit from immune checkpoint inhibitor (ICI) therapies. Methods: In this study, we used a combined cohort (including the GSE41613, GSE65858, TCGA, and CELL cohorts) to identify hub genes significantly associated with ICB and activated CD8 + T-cell gene signatures. We performed single-sample gene set enrichment analysis (ssGSEA) to quantify the expression of hub genes; we then constructed a novel immune signature named "the IMS" that can predict immunotherapy responsiveness, prognosis, immune infiltration, and clinical characteristics. Data from the GSE102349 external cohort and the pembrolizumab cohort obtained from a clinical trial were used to validate the efficiency of the IMS. In addition, we revealed potential mechanisms of the antitumor response by analyzing the HNSCC single-cell database. Finally, we used the LASSO algorithm to build an IMS-related risk model. Results: The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB. Moreover, a tumor microenvironment with a higher IMS underwent remarkable metabolic reprogramming characterized by enrichment in the glycolysis/gluconeogenesis, oxidative phosphorylation, and citrate cycle (TCA cycle) pathways. We also revealed key information on cellular crosstalk between the IMS and other immune lineages, which may mechanistically explain immune escape. In addition, we constructed and validated a risk prediction model (CD2, TBC1D10C, and CD3E) that could stratify HNSCC patients based on survival and response to ICB treatment. Conclusion: IMS is a signature closely correlated with the tumor immune microenvironment. The findings of this study contribute to the understanding of the immune landscape in HNSCC patients. IMS may aid in the clinical management of HNSCC patients through the identification of effective immunotherapies for specific patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Wang and Tan.)

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC., (© 2022. The Author(s).)

Objectives: The aim of this study was to investigate the impact of unified discharge standards on the clinical efficacy and prognosis of hemiarthroplasty in elderly patients with hip fractures., Methods: Retrospective study of 158 elderly patients with hip fractures who underwent artificial femoral head replacement in our hospital from March 2016 to July 2019 were enrolled. According to the unified discharge standards, patients were divided into the observation (65 cases who met discharge criteria) and control group (93 cases who failed to meet all discharge criteria). Histopathological feature, operation status, postoperative Harris Hip score, therapeutic outcome, postoperative complications, readmission and mortality rate were compared between the two groups., Results: Surgery duration and intraoperative blood loss exhibited no difference between the two groups, while transfusion volume and length of hospital stay were significantly increased in the observation group. There was no significant difference in the Harris Hip score between the two groups 12 months postoperatively. The incidence of postoperative complications during the follow-up period was notably lower in the observation group. In addition, the three-month readmission rate and one-year mortality rate were significantly lower in the observation group., Conclusions: For elderly patients with hip fractures undergoing artificial femoral head replacement, the incidence of postoperative complications and postoperative readmission/mortality rate could be reduced through the establishment of unified discharge standards, which should be used in future clinical practice., Competing Interests: None., (AJTR Copyright © 2022.)

Background: COVID-19 has brought greater workload pressures to the medical field, such as medical staff being required to wear personal protective equipment (PPE). While PPE can protect the safety of staff during the pandemic, it can also accelerate the accumulation of fatigue among operators., Objective: This study explores the influence of different protection states on the mental fatigue of nurses., Methods: In this study, 10 participants (5 males and 5 females) were randomly selected among applicants to monitor mental fatigue during the nurses' daily work in four different PPE states (low temperature and low protection; low temperature and high protection; high temperature and low protection; high temperature and high protection). The NASA subjective mental fatigue scale was used for subjective evaluation. Reaction time, attention concentration, attention distribution, memory, and main task completion time were used for objective evaluation., Results: The results demonstrated a significant difference in the effects of different protection states on mental fatigue. The state of high temperature and high protection had the greatest influence on mental fatigue, the state of low temperature and low protection had the least, and states of high (low) temperature and low (high) protection had intermediate effects on mental fatigue. Furthermore, the correlation between the subjective and objective fatigue indices was analyzed using a multiple regression model., Conclusion: This study clarified the influence of different protection states on the mental fatigue of nurses, and verified that nurses require more time and energy to complete the same work as before under high protection states. It provides a basis for evaluating the mental fatigue of nurses in the unique period of the COVID-19 pandemic and specific ideas for optimizing the nursing process., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 Jin et al.)