Designed endocytosis-inducing proteins degrade targets and amplify signals.

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras1,2 (LYTACs) and cytokine receptor-targeting chimeras3 (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor. Here we describe computational design approaches for endocytosis-triggering binding proteins (EndoTags) that overcome these challenges. We present EndoTags for insulin-like growth factor 2 receptor (IGF2R) and asialoglycoprotein receptor (ASGPR), sortilin and transferrin receptors, and show that fusing these tags to soluble or transmembrane target protein binders leads to lysosomal trafficking and target degradation. As these receptors have different tissue distributions, the different EndoTags could enable targeting of degradation to different tissues. EndoTag fusion to a PD-L1 antibody considerably increases efficacy in a mouse tumour model compared to antibody alone. The modularity and genetic encodability of EndoTags enables AND gate control for higher-specificity targeted degradation, and the localized secretion of degraders from engineered cells. By promoting endocytosis, EndoTag fusion increases signalling through an engineered ligand-receptor system by nearly 100-fold. EndoTags have considerable therapeutic potential as targeted degradation inducers, signalling activators for endocytosis-dependent pathways, and cellular uptake inducers for targeted antibody-drug and antibody-RNA conjugates.

The rRNA m6A methyltransferase METTL5 is involved in pluripotency and developmental programs.

Covalent chemical modifications of cellular RNAs directly impact all biological processes. However, our mechanistic understanding of the enzymes catalyzing these modifications, their substrates and biological functions, remains vague. Amongst RNA modifications N6-methyladenosine (m6A) is widespread and found in messenger (mRNA), ribosomal (rRNA), and noncoding RNAs. Here, we undertook a systematic screen to uncover new RNA methyltransferases. We demonstrate that the methyltransferase-like 5 (METTL5) protein catalyzes m6A in 18S rRNA at position A1832 We report that absence of Mettl5 in mouse embryonic stem cells (mESCs) results in a decrease in global translation rate, spontaneous loss of pluripotency, and compromised differentiation potential. METTL5-deficient mice are born at non-Mendelian rates and develop morphological and behavioral abnormalities. Importantly, mice lacking METTL5 recapitulate symptoms of patients with DNA variants in METTL5, thereby providing a new mouse disease model. Overall, our biochemical, molecular, and in vivo characterization highlights the importance of m6A in rRNA in stemness, differentiation, development, and diseases.

The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Enhanced neural synchronization during social communications between dyads with high autistic traits.

Autism is characterized by atypical social communication styles. To investigate whether individuals with high autistic traits could still have effective social communication among each other, we compared the behavioral patterns and communication quality within 64 dyads of college students paired with both high, both low, and mixed high-low (HL) autistic traits, with their gender matched. Results revealed that the high-high (HH) autistic dyads exhibited atypical behavioral patterns during conversations, including reduced mutual gaze, communicational turns, and emotional sharing compared with the low-low and/or HL autistic dyads. However, the HH autistic dyads displayed enhanced interpersonal neural synchronization during social communications measured by functional near-infrared spectroscopy, suggesting an effective communication style. Besides, they also provided more positive subjective evaluations of the conversations. These findings highlight the potential for alternative pathways to effectively communicate with the autistic community, contribute to a deeper understanding of how high autistic traits influence social communication dynamics among autistic individuals, and provide important insights for the clinical practices for supporting autistic people.

Proximal binding of dCas9 at a DNA double strand break stimulates homology-directed repair as a local inhibitor of classical non-homologous end joining.

In CRISPR/Cas9 genome editing, the tight and persistent target binding of Cas9 provides an opportunity for efficient genetic and epigenetic modification on genome. In particular, technologies based on catalytically dead Cas9 (dCas9) have been developed to enable genomic regulation and live imaging in a site-specific manner. While post-cleavage target residence of CRISPR/Cas9 could alter the pathway choice in repair of Cas9-induced DNA double strand breaks (DSBs), it is possible that dCas9 residing adjacent to a break may also determine the repair pathway for this DSB, providing an opportunity to control genome editing. Here, we found that loading dCas9 onto a DSB-adjacent site stimulated homology-directed repair (HDR) of this DSB by locally blocking recruitment of classical non-homologous end-joining (c-NHEJ) factors and suppressing c-NHEJ in mammalian cells. We further repurposed dCas9 proximal binding to increase HDR-mediated CRISPR genome editing by up to 4-fold while avoiding exacerbation of off-target effects. This dCas9-based local inhibitor provided a novel strategy of c-NHEJ inhibition in CRISPR genome editing in place of small molecule c-NHEJ inhibitors, which are often used to increase HDR-mediated genome editing but undesirably exacerbate off-target effects.

Solidophobic Surface for Electrochemical Extraction of High-Valued Mg(OH)2 Coupled with H2 Production from Seawater.

A significant challenge in direct seawater electrolysis is the rapid deactivation of the cathode due to the large scaling of Mg(OH)2. Herein, we synthesized a Pt-coated highly disordered NiCu alloy (Pt-NiCu alloy) electrode with superior solidophobic behavior, enabling stable hydrogen generation (100 mA cm-2, >1000 h durability) and simultaneous production of Mg(OH)2 (>99.0% purity) in electrolyte enriched with Mg2+ and Ca2+. The unconventional solidophobic property primarily stems from the high surface energy of the NiCu alloy substrate, which facilitates the adsorption of surface water and thereby compels the bulk formation of Mg(OH)2 via homogeneous nucleation. The discovery of this solidophobic electrode will revolutionarily simplify the existing techniques for seawater electrolysis and increase the economic viability for seawater electrolysis.

Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.

Microglial HO-1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co-located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG-mediated autophagy and HO-1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf-A1 or HO-1 inhibitor ZnPP protected against hemin-induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG-mediated autophagy and HO-1 signalling pathway. Knock-down of FoxO3a inhibited autophagy and prevented hemin-induced ferroptosis dependent of HO-1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO-1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro-inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis-induced striatum injury in the autologous blood-induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG-mediated autophagy and HO-1 play an important role in microglial activation and ferroptosis-induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.

Emerging connectivity of programmed cell death pathways and pulmonary vascular remodelling during pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD-associated drug targets for PH.

Homologous Peptide Foldamer Promotes FUS Aggregation and Triggers Cancer Cell Death.

Fused in sarcoma (FUS), a multifunctional deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)-binding protein, has been implicated in various cancer types, including sarcoma and leukemia. Despite its association with these diseases, there has been limited exploration of FUS as a cancer therapy target, primarily because its dynamic nature makes it difficult to target specifically. In this study, we explored a kind of ß-sheet peptide foldamer, named ß4-TAT, to influence FUS aggregation by targeting its RNA recognition motifs (RRM). This approach leverages the noncovalent interaction characteristics of peptide self-assembly processes. The ß4 sequence, derived from the FUS RRM ß-sheet, in combination with TAT, a peptide known for its nuclear targeting capability, enables ß4-TAT to bind specifically to the analogous ß4 sequence within FUS. Notably, ß4-TAT effectively induces FUS aggregation within cells, leading to the death of cancer cells. Our work developed a novel peptide foldamer-based strategy for inducing protein aggregation, paving the way for innovative therapeutic approaches in targeting FUS-associated cancers.

Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

Bioinformatics analysis and experimental validation reveal the anti-ferroptosis effect of FZD7 in acute kidney injury.

BACKGROUND: Ferroptosis plays an important role in acute kidney injury (AKI), but the specific regulatory mechanism of ferroptosis in AKI remains unclear. This study is expected to analyze ferroptosis-related genes (FRGs) in AKI and explore their underlying mechanisms. RESULTS: A total of 479 differentially expressed genes (DEGs), including 196 up-regulated genes and 283 down-regulated genes were identified in the AKI chip GSE30718. 341 FRGs were obtained from the Genecard, OMIM and NCBI database. Totally 11 ferroptosis-related DEGs in AKI were found, in which 7 genes (CD44, TIGAR, RB1, LCN2, JUN, ARNTL, ACSL4) were up-regulated and 4 genes (FZD7, EP300, FOXC1, DLST) were down-regulated. Three core genes (FZD7, JUN, EP300) were obtained by PPI and KEGG analysis, among which the function of FZD7 in AKI is unclear. The WGCNA analysis found that FZD7 belongs to a module that was negatively correlated with AKI. Further basic experiments confirmed that FZD7 is down-regulated in mouse model of ischemia-reperfusion-AKI and cellular model of hypoxia-reoxygenation(H/R). In addition, knockdown of FZD7 could further aggravate the down-regulation of cell viability induced by H/R and Erastin, while overexpression of FZD7 can rescue its down-regulation to some extent. Furthermore, we verified that knockdown of FZD7 decreased the expression of GPX4 and overexpression of FZD7 increased the expression of GPX4, suggesting that FZD7 may inhibit ferroptosis by regulating the expression of GPX4 and plays a vital role in the onset and development of AKI. CONCLUSIONS: This article revealed the anti-ferroptosis effect of FZD7 in acute kidney injury through bioinformatics analysis and experimental validation, suggesting that FZD7 is a promising target for AKI and provided more evidence about the vital role of ferroptosis in AKI.

Preparation and preliminary application of fluorescent microsphere test strips for feline parvovirus antibodies.

This study introduces a novel diagnostic modality for the detection of feline panleukopenia virus (FPV) antibodies in feline serum by using fluorescent microsphere immunochromatographic test strips (FM-ICTS). Leveraging the inherent specificity of antigen-antibody interactions, the FM-ICTS approach demonstrates considerable potential for efficient and accurate FPV antibody detection within a short timeframe. The FM-ICTS method demonstrates strong diagnostic performance, with consistent accuracy and stability over time. PBS buffer dilution enables detection across the range of FPV antibody haemagglutination inhibition (HI) titres in both healthy and immunized or infected cats. A high correlation (R² = 0.9733) between the T/C ratio and FPV antibody titres confirms the method's effectiveness in quantifying these titres. Clinical validation with 84 samples supports its reliability by matching results with HI assays. Additionally, stability tests show that the test strips maintain performance during storage, with a coefficient of variation (CV) below 12% over three months at 25℃. This innovative FM-ICTS framework emerges as a promising avenue for expedient and dependable disease diagnosis within the realm of veterinary science, offering implications for timely disease management and surveillance.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

Multi-omics analysis reveals genes and metabolites involved in Streptococcus suis biofilm formation.

BACKGROUND: Streptococcus suis is an important zoonotic pathogen. Biofilm formation largely explains the difficulty in preventing and controlling S. suis. However, little is known about the molecular mechanism of S. suis biofilm formation. RESULTS: In this study, transcriptomic and metabolomic analyses of S. suis in biofilm and planktonic states were performed to identify key genes and metabolites involved in biofilm formation. A total of 789 differential genes and 365 differential metabolites were identified. By integrating transcriptomics and metabolomics, five main metabolic pathways were identified, including amino acid pathway, nucleotide metabolism pathway, carbon metabolism pathway, vitamin and cofactor metabolism pathway, and aminoacyl-tRNA biosynthesis metabolic pathway. CONCLUSIONS: These results provide new insights for exploring the molecular mechanism of S. suis biofilm formation.

Aberrant accumulation of ceramides in mitochondria triggers cell death by inducing autophagy in Arabidopsis.

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.

Evaluation of the protective efficacy of three novel identified membrane associated proteins of Streptococcus suis serotype 2.

Streptococcus suis is one of the major pathogens of pigs circulating worldwide, and the development of vaccines will help to effectively control streptococcosis in swine. In this study, we evaluated the potential of three membrane associated proteins, histidine kinase (HK), glycosyltransferase family 2 (Gtf-2) and phosphate binding protein (PsbP) of S. suis as subunit vaccines. Bioinformatics analysis shows that protein ABC is highly conserved in S. suis. To verify the protective effects of these proteins in animal models, recombinant protein HK, Gtf-2 and PsbP were used to immunize BALB/c mice separately. The results showed that these proteins immunization in mice can effectively induce strong humoral immune responses, protect mice from cytokine storms caused by S. suis infection, and have a significant protective effect against lethal doses of S. suis infection. Furthermore, antibodies with opsonic activity exist in the recombinant proteins antiserum to assist phagocytic cells in killing S. suis. Overall, these results indicated that these recombinant proteins all elicit good immune protective effect against S. suis infection and can be represent promising candidate antigens for subunit vaccines against S. suis.

Dietary administration of Bacillus amyloliquefaciens AV5 on antioxidant activity, blood parameters, and stress responses of Nile tilapia (Oreochromis niloticus) raised under hypoxia and temperature variability.

The inability of Nile tilapia to tolerate hypoxia, as well as low and high temperatures, presents a significant economic concern, as it adversely affects their growth and leads to increased mortality rates. A 42-day feeding trial was conducted to evaluate the impact of adding Bacillus amyloliquefaciens AV5 to a fish meal on the physiological response of Nile tilapia. Three meals were administered to fish (23.4 ± 0.3g) in triplicates. The diets included GC (without B. amyloliquefaciens AV5), G1 (106cfu/g), and G2 (108cfu/g). After the treatment trial, we assessed the antioxidant parameters, hemato-immunological indices, and stress-related genes in O. niloticus. Subsequently, we subjected the fish to hypoxia for 20h and low and high temperatures for 3h each. The findings demonstrated a significant rise in white blood cells, red blood cells, haemoglobin, and hematocrit levels in the blood of fish that were fed a meal supplemented with B. amyloliquefaciens AV5, compared to the control group (GC) (P<0.05) and compared to the control group, the serum of all fish groups that were supplemented with B. amyloliquefaciens AV5 exhibited an increase in catalase, total antioxidant capacity and superoxide dismutase activity and a decrease in lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, pyruvate kinase, myeloperoxidase, glucose, cortisol (P< 0.05). In addition, all fish diet groups that received B. amyloliquefaciens AV5 as a supplement exhibited elevated levels of HIF-1α and HSP70 expression in their livers (P<0.05). Nile tilapia in the G2 diet, exhibited improved values in most evaluated indices under various stress settings (P<0.05). These data indicate that the G2 supplement may be used as a preventive measure to weaken the impacts of environmental stress on O. niloticus.

AI-2 quorum sensing-induced galactose metabolism activation in Streptococcus suis enhances capsular polysaccharide-associated virulence.

Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.

Smartphone GPS-Based Exposure to Greenspace and Walkability and Accelerometer-Assessed Physical Activity During Pregnancy and Early Postpartum-Evidence from the MADRES Cohort.

A growing number of studies have associated walkability and greenspace exposure with greater physical activity (PA) in women during pregnancy. However, most studies have focused on examining women's residential environments and neglected exposure in locations outside the home neighborhood. Using 350 person-days (N = 55 participants) of smartphone global positioning system (GPS) location and accelerometer data collected during the first and third trimesters and 4-6 months postpartum from 55 Hispanic pregnant women from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we examined the day-level effect of women's exposure to walkability and greenspace on their PA outcomes during pregnancy and in the early postpartum period. Moderate-to-vigorous physical activity [MVPA] minutes per day was assessed using accelerometers. Walkability and greenspace were measured using geographic information systems (GIS) within women's daily activity spaces (i.e., places visited and routes taken) recorded using a smartphone GPS and weighted by time spent. We used a generalized linear mixed-effects model to estimate the effects of daily GPS-derived environmental exposures on day-level MVPA minutes. Results showed that women engaged in 23% more MVPA minutes on days when they had some versus no exposure to parks and open spaces in activity spaces (b = 1.23; 95%CI: 1.02-1.48). In addition, protective effects of daily greenspace and walkability exposure on MVPA were stronger in the first and third trimesters, among first-time mothers, and among women who had high pre-pregnancy body mass index (BMI) and lived in least-safe neighborhoods. Our results suggest that daily greenspace and walkability exposure are important for women's PA and associated health outcomes during pregnancy and early postpartum.

Serum neurofilament light chain levels are associated with depression among US adults: a cross-sectional analysis among US adults, 2013-2014.

BACKGROUND: Serum neurofilament light chain (sNfL) has been identified as a biomarker for neurologic diseases. However, sNfL remains unknown to be responsible for depression. AIMS: The aim of this research was to explore the relationship between sNfL levels and depression in US adults. METHODS: In this cross-sectional survey of the general population, we investigated representative data involving 10,175 participants from the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Depression was diagnosed using the Patient Health Questionnaire-9 (PHQ-9). The effect of related factors on depression was analyzed by conducting a univariate analysis. Stratified analysis was utilized to detect the stability and sensitivity of the relationship. After adjusting for race, education, marital status, smoking status, body mass index (BMI), sleep duration, income, and a history of hypertension, sedentary behavior and stroke, multivariable linear regression was performed to demonstrate the correlation between sNfL and depression. RESULTS: A total of 1301 individuals between the ages of 20 and 75 were involved in this investigation, of which 108 (8.3%) were diagnosed with depression. A significant positive correlation between sNfL and depression among adults in the US was observed by conducting univariable analyses. After adjusting for confounding factors, the multivariate analyses indicated that elevated sNfL levels might play a pivotal role in the development of depression (odds ratio (OR) = 3.0; 95% confidence interval (CI): (1.5, 6.1), P = 0.002). CONCLUSION: These results indicated that sNfL is closely linked to depression in a nationally representative individual. However, further studies are needed to confirm the biological mechanism as well as the clinical implications of sNfL and depression.