A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation.

The coronavirus disease 2019 (COVID-19) pandemic underscores the need to better understand animal-to-human transmission of coronaviruses and adaptive evolution within new hosts. We scanned more than 182,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes for selective sweep signatures and found a distinct footprint of positive selection located around a non-synonymous change (A1114G; T372A) within the spike protein receptor-binding domain (RBD), predicted to remove glycosylation and increase binding to human ACE2 (hACE2), the cellular receptor. This change is present in all human SARS-CoV-2 sequences but not in closely related viruses from bats and pangolins. As predicted, T372A RBD bound hACE2 with higher affinity in experimental binding assays. We engineered the reversion mutant (A372T) and found that A372 (wild-type [WT]-SARS-CoV-2) enhanced replication in human lung cells relative to its putative ancestral variant (T372), an effect that was 20 times greater than the well-known D614G mutation. Our findings suggest that this mutation likely contributed to SARS-CoV-2 emergence from animal reservoirs or enabled sustained human-to-human transmission.

A conserved viral amphipathic helix governs the replication site-specific membrane association.

Positive-strand RNA viruses assemble their viral replication complexes (VRCs) on specific host organelle membranes, yet it is unclear how viral replication proteins recognize and what motifs or domains in viral replication proteins determine their destinations. We show here that an amphipathic helix, helix B in replication protein 1a of brome mosaic virus (BMV), is necessary for 1a's localization to the nuclear endoplasmic reticulum (ER) membrane where BMV assembles its VRCs. Helix B is also sufficient to target soluble proteins to the nuclear ER membrane in yeast and plant cells. We further show that an equivalent helix in several plant- and human-infecting viruses of the Alsuviricetes class targets fluorescent proteins to the organelle membranes where they form their VRCs, including ER, vacuole, and Golgi membranes. Our work reveals a conserved helix that governs the localization of VRCs among a group of viruses and points to a possible target for developing broad-spectrum antiviral strategies.

Association between remnant cholesterol and the risk of 4 site-specific cancers: evidence from a cross-sectional and Mendelian randomization study.

BACKGROUND: Recent studies have implicated remnant cholesterol (RC) in the etiology, progression, and prognosis of cancer. However, very few of them concentrated on the study of the precise relationship between serum RC levels and cancer risk, leaving this subject unexplored. Consequently, this study aims to investigate the association between serum RC levels and 4 site-specific cancers, employing a dual approach that combines observational and mendelian randomization (MR) analysis. METHODS: Based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020, this study collected data from18,067 participants. To rule out confounders, this study utilized weighted multivariable logistic regression and assessed non-linear associations using restricted cubic spline (RCS) regression, followed by two-piecewise linear regression. Sensitivity analysis conducted in this study included subgroup analysis, multiple imputation, outlier removal, and propensity score matching. To strengthen causal inference, this study employed univariable and multivariable MR analysis. The robustness and reliability of the findings were estimated by the application of replication and meta-analysis. RESULTS: The results of multivariable logistic regression analysis demonstrated a significant association between serum RC levels and breast cancer, showing that individuals in the higher logRC category had a higher risk of breast cancer compared to those in the lower category (Q3 vs. Q1: OR = 1.71, 95% CI: 1.01-2.88, P = 0.044). Weighted RCS revealed an inverted L-shape association between RC and the risk of breast cancer (P-nonlinear = 0.0386, P-overall = 0.010). Primary MR analysis provided evidence for an increased risk of breast (IVW: OR = 1.08, 95% CI: 1.03-1.12, P = 0.000951) and colorectal cancer (IVW: OR = 1.12, 95% CI: 1.00-1.24, P = 0.0476) associated with RC. However, the results of replication and meta-analysis did not support a significant causal association of RC with the risk of breast cancer (OR = 1.04, 95% CI: 0.95-1.13), lung cancer (OR = 0.95, 95% CI: 0.88-1.03), colorectal cancer (OR = 1.05, 95% CI: 0.92-1.19), and prostate cancer (OR = 1.01, 95% CI: 0.95-1.08). CONCLUSION: Although a non-linear relationship was observed in the cross-sectional study between remnant cholesterol levels and breast cancer risk, MR analyses failed to provide any causal evidence.

Meta-Analysis of eVisit Technology on Psychological Anxiety and Factors Influencing the Parents of NICU Newborns.

BACKGROUND: Due to the geographical distance, work obligations, and parenting responsibilities, it is often difficult for parents to visit the neonatal intensive care unit (NICU). Limited parent presence might also constrain updates about infant status thus increasing anxiety, which potentially leads to a stronger necessity for visitation. PURPOSE: Examine the evidence for use of electronic visit (eVisit) technology for parents of newborns in NICU, for example, do eVisits decrease anxiety and are there other factors that demonstrate effectiveness. DATA SOURCES: Seven databases were used to search for evidence from 1 January 2000 to 13 November 2023. STUDY SELECTION: Studies were included with terms related to eHealth, NICU, infant, parent and 41 eligible studies were assessed. DATA EXTRACTION: Data were extracted by 2 reviewers with a systematic-staged review approach. RESULTS: Eight studies with a total of 1450 cases were included. Results of meta-analysis showed that eVisit technology improved anxiety compared with conventional visitation (MD = - 5.04, 95% CI [-5.92, - 4.17], P < .01) and hospitalization satisfaction (RR = 1.09, 95% CI [1.05, 1.13], P < .01), but the effect was not significant with regard to reduction in infant length of stay (MD = - 1.07, 95% CI [-5.39, 3.25], P = .63). IMPLICATIONS FOR PRACTICE AND RESEARCH: A large sample, high-quality, multi-centered randomized controlled study needs to be conducted to validate the effect of eVisit technology on the psychological state of parents, implications for nursing practice as well as potential newborn affects to improve future ease of use. VIDEO ABSTRACT: Available for more insights from the authors. This video shows the concept, current status, significance, and implications for practice and research of eVisit technology.

The Experience and Needs of Living With Home Parenteral Nutrition in Adult Patients: A Meta-Synthesis of Qualitative Studies.

BACKGROUND: Home parenteral nutrition (HPN) can improve the nutritional status of patients with gastrointestinal dysfunction. However, some patients face a series of challenges during its implementation, which significantly affect their quality of life. AIMS: To explore the experience and needs of living with home parenteral nutrition in adult patients. DESIGN: A systematic review and meta-synthesis. METHODS: A search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database and Wipu Database, to explore the real-life experiences and needs of adult patients receiving HPN. The search covered the period up to March 2024. Qualitative research quality was evaluated using the Joanna Briggs Institute's Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. Data synthesis was performed using Thomas and Harden's method of thematic and content analysis. RESULTS: Twelve studies, each offering qualitative data, were analysed, resulting in the identification of four themes: positive experiences of HPN; the interplay of dynamic changes across physical, mental and social levels; self-adjustment to the new normal; and multidimensional needs of patients receiving HPN. CONCLUSIONS: Patients receiving HPN face multiple challenges physically, psychologically and socially. This paper also reveals the supportive needs of patients in adapting to a new lifestyle with HPN. This indicates that healthcare professionals should provide comprehensive, continuous and dynamic supportive medical services to facilitate patients' reintegration and return to normal social life. PATIENT AND PUBLIC INVOLVEMENT: As this study constitutes a meta-synthesis, patient or public contribution is not applicable. REPORTING APPROACH: Adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines, this meta-synthesis was conducted.

Systematic Review and Meta-Analysis of Effectiveness of Acceptance and Commitment Therapy in Patients With Breast Cancer.

BACKGROUND: The physical and psychological well-being of patients with breast cancer is an important global issue. Acceptance and commitment therapy (ACT) aims to equip patients with the skills to respond and adapt to difficult circumstances. However, the extent of the physical and psychological outcomes of this therapy in patients with breast cancer remains unclear. OBJECTIVES: The aim of the study was to summarize available evidence and assess the efficacy of ACT on physiological and psychological outcomes in patients with breast cancer. METHODS: Published randomized controlled studies were identified in MEDLINE, PsycInfo, Embase, Web of Science, CINAHL, and CNKI from inception to December 2019 and Cochrane Library, AMED, and Clinical trials.gov from inception to September 2020. Methodological rigor was assessed by two reviewers using the Cochrane Handbook for Systematic Review of Interventions. Sufficient data were statistically pooled with review manager; otherwise, a narrative summary was used. RESULTS: Thirteen trials were included in the review. Methodological quality varied across the studies. Meta-analyses demonstrated that ACT had moderate to large effects on reducing anxiety, depression, and stress and improving hope. Sensitivity analyses reached results similar to those of the meta-analyses. However, the effects of ACT on the physiological symptoms, fear of cancer recurrence, and psychological flexibility of patients with breast cancer remain inconclusive. DISCUSSION: ACT has beneficial effects on the anxiety, depression, stress, and hope of patients with breast cancer. The evidence of ACT on physiological symptoms, fear of cancer recurrence, and psychological flexibility needs to be treated with caution. Further studies are needed and should consider different delivery forms and also explore the mechanisms of each component of ACT under different cultural contexts.

An engineered mutant of a host phospholipid synthesis gene inhibits viral replication without compromising host fitness.

Viral infections universally rely on numerous hijacked host factors to be successful. It is therefore possible to control viral infections by manipulating host factors that are critical for viral replication. Given that host genes may play essential roles in certain cellular processes, any successful manipulations for virus control should cause no or mild effects on host fitness. We previously showed that a group of positive-strand RNA viruses enrich phosphatidylcholine (PC) at the sites of viral replication. Specifically, brome mosaic virus (BMV) replication protein 1a interacts with and recruits a PC synthesis enzyme, phosphatidylethanolamine methyltransferase, Cho2p, to the viral replication sites that are assembled on the perinuclear endoplasmic reticulum (ER) membrane. Deletion of the CHO2 gene inhibited BMV replication by 5-fold; however, it slowed down host cell growth as well. Here, we show that an engineered Cho2p mutant supports general PC synthesis and normal cell growth but blocks BMV replication. This mutant interacts and colocalizes with BMV 1a but prevents BMV 1a from localizing to the perinuclear ER membrane. The mislocalized BMV 1a fails to induce the formation of viral replication complexes. Our study demonstrates an effective antiviral strategy in which a host lipid synthesis gene is engineered to control viral replication without comprising host growth.

Host Pah1p phosphatidate phosphatase limits viral replication by regulating phospholipid synthesis.

Replication of positive-strand RNA viruses [(+)RNA viruses] takes place in membrane-bound viral replication complexes (VRCs). Formation of VRCs requires virus-mediated manipulation of cellular lipid synthesis. Here, we report significantly enhanced brome mosaic virus (BMV) replication and much improved cell growth in yeast cells lacking PAH1 (pah1Δ), the sole yeast ortholog of human LIPIN genes. PAH1 encodes Pah1p (phosphatidic acid phosphohydrolase), which converts phosphatidate (PA) to diacylglycerol that is subsequently used for the synthesis of the storage lipid triacylglycerol. Inactivation of Pah1p leads to altered lipid composition, including high levels of PA, total phospholipids, ergosterol ester, and free fatty acids, as well as expansion of the nuclear membrane. In pah1Δ cells, BMV replication protein 1a and double-stranded RNA localized to the extended nuclear membrane, there was a significant increase in the number of VRCs formed, and BMV genomic replication increased by 2-fold compared to wild-type cells. In another yeast mutant that lacks both PAH1 and DGK1 (encodes diacylglycerol kinase converting diacylglycerol to PA), which has a normal nuclear membrane but maintains similar lipid compositional changes as in pah1Δ cells, BMV replicated as efficiently as in pah1Δ cells, suggesting that the altered lipid composition was responsible for the enhanced BMV replication. We further showed that increased levels of total phospholipids play an important role because the enhanced BMV replication required active synthesis of phosphatidylcholine, the major membrane phospholipid. Moreover, overexpression of a phosphatidylcholine synthesis gene (CHO2) promoted BMV replication. Conversely, overexpression of PAH1 or plant PAH1 orthologs inhibited BMV replication in yeast or Nicotiana benthamiana plants. Competing with its host for limited resources, BMV inhibited host growth, which was markedly alleviated in pah1Δ cells. Our work suggests that Pah1p promotes storage lipid synthesis and thus represses phospholipid synthesis, which in turn restricts both viral replication and cell growth during viral infection.

A Modified Technique Using Levator Aponeurosis-Müller Muscle-Reinforced Plication for Blepharoptosis Correction.

BACKGROUND: Blepharoptosis is a common and challenging clinical problem for oculoplastic surgeons, and various surgical techniques have been used to correct ptosis. The aims of this study were to present the clinical results of a modified technique using levator aponeurosis-Müller muscle-reinforced plication for blepharoptosis correction and to demonstrate its advantages over conventional advancement or plication methods. METHODS: This study was conducted in the Plastic Surgery Department of Sir Run Run Shaw Hospital between April 2017 and September 2018. By using this modified technique, the levator-Müller complex was reinforced with a plication suture that pierced under and through the levator-Müller complex, and the posterior and lower part of the levator-Müller complex was advanced to the tarsus, which provided permanent, reliable adhesion. The primary outcome was marginal reflex distance 1 preoperatively and postoperatively. Secondary outcomes were the cosmetic outcome, complications, and operative time. RESULTS: Eighty-six patients (169 eyelids) underwent this modified surgery. Patients' average age was 26 ± 7.6 years, and the median follow-up was 14 months. The preoperative and postoperative mean marginal reflex distance 1 values were 1.72 ± 0.32 and 3.69 ± 0.28 mm, respectively. The amount of plication ranged from 4 to 15 mm. The overall surgical success rate was 88.17%. Some complications were observed including undercorrection (5.92%), asymmetry (4.73%), lagophthalmos (0.59%), and conjunctival prolapse (0.59%). CONCLUSIONS: The modified technique provided good functional and cosmetic outcomes for blepharoptosis correction by avoiding unpredicted adhesion, and it has its advantages including simplicity, easy adjustment of the eyelid height intraoperatively, minimal edema formation, and high success rate.

Integrating network pharmacology and computational biology to propose Yiqi Sanjie formula's mechanisms in treating NSCLC: molecular docking, ADMET, and molecular dynamics simulation.

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths globally. Current treatments often do not fully meet efficacy and quality of life expectations. Traditional Chinese medicine (TCM), particularly the Yiqi Sanjie formula, shows promise but lacks clear mechanistic understanding. This study addresses this gap by investigating the therapeutic effects and underlying mechanisms of Yiqi Sanjie formula in NSCLC. Methods: We utilized network pharmacology to identify potential NSCLC drug targets of the Yiqi Sanjie formula via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Compounds with favorable oral bioavailability and drug-likeness scores were selected. Molecular docking was conducted using AutoDock Vina with structural data from the Protein Data Bank and PubChem. Molecular dynamics (MD) simulations were performed with Desmond Molecular Dynamics System, analyzing interactions up to 500 nanoseconds using the OPLS4 force field. ADMET predictions were executed using SwissADME and ADMETlab 2.0, assessing pharmacokinetic properties. Results: Using network pharmacology tools, we performed Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) analysis for protein-protein interaction, Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway enrichment, and gene ontology (GO) for functional enrichment, identifying crucial signaling pathways and biological processes influenced by the hit compounds bifendate, xambioona, and hederagenin. STRING analysis indicated substantial connectivity among the targets, suggesting significant interactions within the cell cycle regulation and growth factor signaling pathways as outlined in our KEGG results. The GO analysis highlighted their involvement in critical biological processes such as cell cycle control, apoptosis, and drug response. Molecular docking simulations quantified the binding efficiencies of the identified compounds with their targets-CCND1, CDK4, and EGFR-selected based on high docking scores that suggest strong potential interactions crucial for NSCLC inhibition. Subsequent MD simulations validated the stability of these complexes, supporting their potential as therapeutic interventions. Additionally, the novel identification of ADH1B as a target underscores its prospective significance in NSCLC therapy, further expanded by our comprehensive bioinformatics approach. Conclusions: Our research demonstrates the potential of integrating network pharmacology and computational biology to elucidate the mechanisms of the Yiqi Sanjie formula in NSCLC treatment. The identified compounds could lead to novel targeted therapies, especially for patients with overexpressed targets. The discovery of ADH1B as a therapeutic target adds a new dimension to NSCLC treatment strategies. Further studies, both in vitro and in vivo, are needed to confirm these computational findings and advance these compounds towards clinical trials.

Advancements in melanoma immunotherapy: the emergence of Extracellular Vesicle Vaccines.

Malignant melanoma represents a particularly aggressive type of skin cancer, originating from the pathological transformation of melanocytes. While conventional interventions such as surgical resection, chemotherapy, and radiation therapy are available, their non-specificity and collateral damage to normal cells has shifted the focus towards immunotherapy as a notable approach. Extracellular vesicles (EVs) are naturally occurring transporters, and are capable of delivering tumor-specific antigens and directly engaging in the immune response. Multiple types of EVs have emerged as promising platforms for melanoma vaccination. The effectiveness of EV-based melanoma vaccines manifests their ability to potentiate the immune response, particularly by activating dendritic cells (DCs) and CD8+ T lymphocytes, through engineering a synergy of antigen presentation and targeted delivery. Here, this review mainly focuses on the construction strategies for EV vaccines from various sources, their effects, and immunological mechanisms in treating melanoma, as well as the shortcomings and future perspectives in this field. These findings will provide novel insights into the innovative exploitation of EV-based vaccines for melanoma immune therapy.

Advances in the Applications of Extracellular Vesicle for the Treatment of Skin Photoaging: A Comprehensive Review.

Skin photoaging is a complex biological process characterized by the accumulation of oxidative damage and structural changes in the skin, resulting from chronic exposure to ultraviolet (UV) radiation. Despite the growing demand for effective treatments, current therapeutic options for skin photoaging remain limited. However, emerging research has highlighted the potential of extracellular vesicles (EVs), including exosomes, micro-vesicles, apoptotic bodies and liposomes, as promising therapeutic agents in skin rejuvenation. EVs are involved in intercellular communication and can deliver bioactive molecules, including proteins, nucleic acids, and lipids, to recipient cells, thereby influencing various cellular processes. This comprehensive review aims to summarize the current research progress in the application of EVs for the treatment of skin photoaging, including their isolation and characterization methods, roles in skin homeostasis, therapeutic potential and clinical applications for skin photoaging. Additionally, challenges and future directions in EVs-based therapies for skin rejuvenation are discussed.

Comparisons of the effects of topical anti-scar drugs on post-surgical facial scar formation: a clinical investigation.

OBJECTIVES: Scarring is a common but intricate problem, and topical anti-scarring drugs are the most widely used treatment. However, the wide range of drugs available makes it difficult for doctors and patients to choose from because of the lack of clinical comparisons. Therefore, we conducted an observational study to compare the clinical efficacy of different topical anti-scarring drugs. METHODS: Patients with post-suturing facial scars were enrolled in this study. The questionnaire was designed to record the basic characteristics of the patients. The Vancouver Scar Scale, SCAR scale, and measurements of scar width and thickness were used to evaluate scar quality. Patients who met the inclusion criteria were divided into four groups for comparison: the silicone preparation (SP), onion extract (OE), asiaticoside (AC) groups, and the untreated blank control (BC) group. The overall data were analyzed before they were confined to the zygomatic region. RESULTS: A total of 127 eligible patients were enrolled in this study. The results of the total and zygomatic scars demonstrated that SP, OE, and AC groups resulted in narrower scars and lower scar scale scores. The SP group depicted higher melanin efficacy than the other two groups. The OE group had the best pliability, whereas the AC group had the thinnest scar. CONCLUSIONS: In this study, we acquired expertise with different topical anti-scar agents: SP significantly reduced melanin levels, OE mainly benefited scar pliability, and AC was better at reducing scar thickness. These differences may be more instructive for clinical applications.

Correlates of Sleep Disturbance among Older Adults with Mild Cognitive Impairment: A Cross-Sectional Study.

Individuals with mild cognitive impairment (MCI) are at high risk for dementia development. Sleep disturbance is often overlooked in MCI, although it is an important risk factor of cognitive decline. In the absence of a cure for dementia, managing the risk factors of cognitive decline in MCI is likely to delay disease progression. To develop interventions for sleep disturbance in MCI, its related factors should be explored. This study aimed to identify and compare the correlates of sleep disturbance in older adults with MCI and those in cognitively healthy older adults. A comparative cross-sectional study was adopted. Data were obtained from 219 Chinese community-dwelling older adults (female: 70.3%), which consisted of 127 older adults with MCI and 92 age-matched cognitively healthy controls. The candidate correlates of sleep disturbance included socio-demographic correlates, health-related factors, lifestyle-related factors and psychological factor. Descriptive, correlational and regression statistics were used for data analysis. The prevalence of sleep disturbance in MCI was 70.1% compared to that of 56.5% in cognitively healthy controls (p < 0.001). The multivariate analysis indicated that, in participants with MCI, depressive symptoms (Beta = 0.297, p = 0.001), comorbidity burden (Beta = 0.215, p = 0.012) and physical activity (Beta = -0.297, p = 0.001) were associated with sleep disturbance. However, in the cognitively healthy controls, only depressive symptoms (Beta = 0.264, p = 0.028) and comorbidity burden (Beta = 0.361, p = 0.002) were associated with sleep disturbance. This finding highlights that sleep disturbance is sufficiently prominent to warrant evaluation and management in older adults with MCI. Furthermore, the findings elucidate several important areas to target in interventions aimed at promoting sleep in individuals with MCI.

Decreased Risk in the Pancreatic Cancer With History of Hay Fever: A Meta-Analysis.

Background: An increasing incidence of pancreatic cancer has been observed worldwide over the last few decades. Previous reports suggested that hay fever, a common allergic disease, may function in pancreatic cancer. Data on hay fever as a risk or protective factor for pancreatic cancer was controversial in several case-control reports. So, we here did a meta-analysis on published studies to evaluate the association of hay fever and the risk of pancreatic cancer. Methods: A comprehensive literature search was performed through public databases. The association between hay fever and pancreatic cancer was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). The Cochran's Q test and I2 index were used to evaluate heterogeneity. Results: We included 8 population-based case-control studies involving 10,454 participants from 1986 to 2014. A history of hay fever was associated with a decreased risk of pancreatic cancer (OR, 0.57; 95% CI, 0.50-0.64, P < 0.00001) through fixed effect model. Conclusion: The result of our study suggested that hay fever may significantly decrease the risk of pancreatic cancer.

Role of depressive symptoms in subjective memory complaint in older adults with mild cognitive impairment.

AIMS: To explore the independent relationship between depressive symptoms and subjective memory complaint (SMC) amongst older adults with mild cognitive impairment (MCI) after adjusting for objective cognitive function and other important confounding factors. BACKGROUND: subjective memory complaint is a core symptom of MCI and is often the primary reason for older adults with MCI to seek for medical help. Improving subjective memory amongst older adults with MCI is important to enhance their quality of life and potentially delay further cognitive decline. Depressive symptoms, which are highly prevalent neuropsychiatric symptoms amongst older adults with MCI, may be one of the reasons that affect an individual's self-perception of memory function. However, there is a dearth of studies to provide a thorough evaluation of the independent relationship between depressive symptoms and SMC amongst older adults with MCI. DESIGN: A descriptive correlational study. METHODS: A consecutive sample (N = 154) of adults aged over 60 years was recruited from a community healthcare centre between June and September 2016. MCI was detected using the Montreal Cognitive Assessment. Depressive symptoms and subjective memory were measured using the Geriatric Depression Scale and Memory Inventory for the Chinese, respectively. Hierarchical regression was performed to explore the relationship between SMC and depressive symptoms, with control over objective cognitive function, socio-demographic and health-related confounding factors. RESULTS: After controlling objective cognitive function and other confounding factors, SMC was independently associated with depressive symptoms (standardised ß = 0.336, p < .001). This psychological status even explained for a greater variance (R2  = 8.8%) for SMC compared with objective cognitive function (R2  = 2.4%). CONCLUSION: subjective memory complaint was independently associated with depressive symptoms in older adults with MCI. Early detection and management of depressive symptoms are highly important amongst this clinical cohort. IMPLICATIONS FOR PRACTICE: Early detection and prompt treatment of depressive symptoms is a highly prioritised care agenda in managing SMC in older adults with MCI.

An Amphipathic Alpha-Helix Domain from Poliovirus 2C Protein Tubulate Lipid Vesicles.

Positive-strand RNA viruses universally remodel host intracellular membranes to form membrane-bound viral replication complexes, where viral offspring RNAs are synthesized. In the majority of cases, viral replication proteins are targeted to and play critical roles in the modulation of the designated organelle membranes. Many viral replication proteins do not have transmembrane domains, but contain single or multiple amphipathic alpha-helices. It has been conventionally recognized that these helices serve as an anchor for viral replication protein to be associated with membranes. We report here that a peptide representing the amphipathic α-helix at the N-terminus of the poliovirus 2C protein not only binds to liposomes, but also remodels spherical liposomes into tubules. The membrane remodeling ability of this amphipathic alpha-helix is similar to that recognized in other amphipathic alpha-helices from cellular proteins involved in membrane remodeling, such as BAR domain proteins. Mutations affecting the hydrophobic face of the amphipathic alpha-helix severely compromised membrane remodeling of vesicles with physiologically relevant phospholipid composition. These mutations also affected the ability of poliovirus to form plaques indicative of reduced viral replication, further underscoring the importance of membrane remodeling by the amphipathic alpha-helix in possible relation to the formation of viral replication complexes.

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.

The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Interestingly, co-occurrence of polyprenols and dolichols, i.e. detection of a dolichol along with significant levels of its precursor polyprenol, are unusual in eukaryotic cells. Our metabolomics studies revealed that cis-polyisoprenoids are more diverse in the malaria parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite's development. Moreover, we confirmed the presence of an active cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite.

Correlates of Health-Related Quality of Life Among Chinese Older Adults with Mild Cognitive Impairment.

PURPOSE: This study aimed to assess the health-related quality of life (HRQoL) and identify the important correlates of HRQoL in older Chinese adults with mild cognitive impairment (MCI). PATIENTS AND METHODS: A cross-sectional study design was adopted. A total of 204 older adults with MCI were enrolled in this study. HRQoL was evaluated by the Quality of Life-Alzheimer's disease. Hierarchical regression analysis was conducted to investigate the sociodemographic, disease-related, psychological, and behavioral factors associated with the HRQoL of individuals with MCI. RESULTS: Hierarchical regression analysis indicated that old age (Beta = -0.131, p =0.024), low income (Beta = 0.128, p = 0.032), depressive symptoms (Beta = -0.564, p < 0.001), and poor sleep quality (Beta = -0.169, p =0.004) were significantly associated with the HRQoL of individuals with MCI. CONCLUSION: Caring for older Chinese adults with MCI should focus on sociodemographically disadvantaged groups with advanced age and low income. Rehabilitation programs that effectively alleviate depressive symptoms and improve sleep quality should be applied to older adults with MCI to enhance their HRQoL.

Host Lipids in Positive-Strand RNA Virus Genome Replication.

Membrane association is a hallmark of the genome replication of positive-strand RNA viruses [(+)RNA viruses]. All well-studied (+)RNA viruses remodel host membranes and lipid metabolism through orchestrated virus-host interactions to create a suitable microenvironment to survive and thrive in host cells. Recent research has shown that host lipids, as major components of cellular membranes, play key roles in the replication of multiple (+)RNA viruses. This review focuses on how (+)RNA viruses manipulate host lipid synthesis and metabolism to facilitate their genomic RNA replication, and how interference with the cellular lipid metabolism affects viral replication.