Tracking the hologenome dynamics in aquatic invertebrates by the holo-2bRAD approach.

The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.

Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency.

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Transformation of As and Cd associated with Fe-Mn-modified biochar during simultaneous remediation on the contaminated soil.

Here, Fe- and Mn-modified biochar (BC-Fe-Mn) was applied to simultaneously stabilize As and Cd in the contaminated soil. The removal efficiencies for NaHCO3-extractable As and DTPA-extractable Cd by BC-Fe-Mn were 60.8% and 49.6%, respectively. The speciation analyses showed that the transformation to low-crystallinity Fe-bound (F3) As, Fe-Mn oxide-bound (OX) of Cd, and residual As and Cd was primarily attributed to stabilizing the two metal(loid)s. Moreover, the correlation analyses showed that the increase of As in F3 fraction was significantly and positively associated with the increase of OX fraction Mn (r = 0.64). Similarly, OX fraction Cd was increased notably with increasing OX fraction Fe (r = 0.91) and OX fraction Mn (r = 0.76). In addition, a novel dialysis experiment was performed to separate the reacted BC-Fe-Mn from the soil for intensively investigating the stabilization mechanisms for As and Cd by BC-Fe-Mn. The characteristic crystalline compounds of (Fe0.67Mn0.33)OOH and Fe2O3 on the surface of BC-Fe-Mn were revealed by SEM-EDS and XRD. And FTIR analyses showed that α-FeOOH, R-COOFe/Mn+, and O-H on BC-Fe-Mn potentially served as the reaction sites for As and Cd. A crystalline compound of MnAsO4 was found in the soil treated by BC-Fe-Mn in the dialysis experiment. Thus, our results are beneficial to deeper understand the mechanisms of simultaneous stabilization of As and Cd by BC-Fe-Mn in soil and support the application of the materials on a large scale.

Comparing the efficacy of traditional Chinese exercises and general aerobic exercises in university students with sleep disorders: A systematic review and meta-analysis.

BACKGROUND: The objective of this study was to compare the impact of traditional Chinese exercise (TCEs) and general aerobic exercise (GAEs) on the sleep quality of university students and to determine which exercise is more effective in improving sleep quality in this specific population. METHODS: We utilized Review Manager 5.3 to analyze data from 21 randomized controlled trials (RCTs), which included a total of 1252 participants. Effect sizes of TCEs and GAEs were compared using a random-effects model. Subgroup analyses were conducted on 3 modulating variables: times per session, frequency per week, and period. RESULTS: A Meta-analysis of 14 RCTs showed that both TCEs (standard mean difference [SMD] = -0.89, 95% CI: -1.18 to -0.61; P < .00001) and GAEs (SMD = -1.53, 95% CI: -2.10 to -0.97; P < .00001) can significantly improve the sleep of university students, with a significant difference between TCEs and GAEs (P = .05). Both GAEs and TCEs had positive effects on various aspects of sleep quality, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. A subgroup analysis of aerobic exercise showed that the effect size was larger in the 40 to 60 minutes group compared to the 60 to 90 minutes group (SMD = -1.89; 95% CI: -2.19 to -1.59; P < .00001). Furthermore, the effect size was larger in the 3 to 5 times per week group compared to the 2 times per week group (SMD = -1.56; 95% CI: -2.33 to -0.80; P < .0001). The effect size was also found to be larger in a period of 2 to 4 weeks compared to 6 to 18 weeks (SMD = -1.85; 95% CI: -2.17 to -1.54; P < .00001). CONCLUSION: GAEs is more effective than TCEs in improving the sleep quality of university students. An optimal aerobic exercise regimen for enhancing sleep quality among university students involves engaging in sessions lasting 40~60 minutes, 3~5 times per week, over a duration of 4 weeks.

Crohn's disease-associated IgA nephropathy may prone to better renal outcome.

BACKGROUND AND AIM: Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN). METHODS: Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study. RESULTS: Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m2 vs. 104.53 ± 32.97 ml per min per 1.73m2, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments. CONCLUSIONS: CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.

Planning biosynthetic pathways of target molecules based on metabolic reaction prediction and AND-OR tree search.

Bioretrosynthesis problem is to predict synthetic routes using substrates for given natural products (NPs). However, the huge number of metabolic reactions leads to a combinatorial explosion of searching space, which is high time-consuming and costly. Here, we propose a framework called BioRetro to predict bioretrosynthesis pathways using a one-step bioretrosynthesis network, termed HybridMLP combined with AND-OR tree heuristic search. The HybridMLP predicts precursors that will produce the target NPs, while the AND-OR tree generates the iterative multi-step biosynthetic pathways. The one-step bioretrosynthesis prediction experiments are conducted on MetaNetX dataset by using HybridMLP, which achieves 46.5%, 74.6%, 81.6% in terms of the top-1, top-5, top-10 accuracies. The great performance demonstrates the effectiveness of HybridMLP in one-step bioretrosynthesis. Besides, the evaluation of two benchmark datasets reveals that BioRetro can significantly improve the speed and success rate in predicting biosynthesis pathways. In addition, the BioRetro is further shown to find the synthetic pathway of compounds, such as ginsenoside F1 with the same substrates as reported but different enzymes, which may be the novel potential enzyme to have better catalytic performance.

Alternaria solani effectors AsCEP19 and AsCEP20 reveal novel functions in pathogenicity and conidiogenesis.

Previous work identified a pair of specific effectors AsCEP19 and AsCEP20 in Alternaria solani as contributors to the virulence of A. solani. Here, we constructed AsCEP19 and AsCEP20 deletion mutants in A. solani strain HWC168 to further reveal the effects of these genes on the biology and pathogenicity of A. solani. Deletion of AsCEP19 and AsCEP20 did not affect vegetative growth but did affect conidial maturation, with an increase in the percentage of abnormal conidia produced. Furthermore, we determined the expression patterns of genes involved in the conidiogenesis pathway and found that the regulatory gene abaA was significantly upregulated and chsA, a positive regulator for conidiation, was significantly downregulated in the mutant strains compared to the wild-type strain. These results suggest that AsCEP19 and AsCEP20 indirectly affect the conidial development and maturation of A. solani. Pathogenicity assays revealed significantly impaired virulence of ΔAsCEP19, ΔAsCEP20, and ΔAsCEP19 + AsCEP20 mutants on potato and tomato plants. Moreover, we performed localization assays with green fluorescent protein-tagged proteins in chili pepper leaves. We found that AsCEP19 can specifically localize to the chloroplasts of chili pepper epidermal cells, while AsCEP20 can localize to both chloroplasts and the plasma membrane. Weighted gene co-expression network analysis revealed enrichment of genes of this module in the photosynthesis pathway, with many hub genes associated with chloroplast structure and photosynthesis. These results suggest that chloroplasts are the targets for AsCEP19 and AsCEP20. IMPORTANCE: Alternaria solani is an important necrotrophic pathogen causing potato early blight. Previous studies have provide preliminary evidence that specific effectors AsCEP19 and AsCEP20 contribute to virulence, but their respective functions, localization, and pathogenic mechanisms during the infection process of A. solani remain unclear. Here, we have systematically studied the specific effectors AsCEP19 and AsCEP20 for the first time, which are essential for conidial maturation. The deletion of AsCEP19 and AsCEP20 can significantly impair fungal pathogenicity. Additionally, we preliminarily revealed that AsCEP19 and AsCEP20 target the chloroplasts of host cells. Our findings further enhance our understanding of the molecular mechanisms underlying the virulence of necrotrophic pathogens.

The role of LncRNA-mediated autophagy in cancer progression.

Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis.

Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.

BACKGROUND AND HYPOTHESIS: Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets. STUDY DESIGN: To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders. We applied pleiotropy-informed conditional false discovery rate (pleioFDR) analysis to identify common risk genetic loci for SCZ and BD-I. Additionally, we performed a cell-type-specific analysis in the human brain to detect risk genes notably enriched in distinct brain cell types. The impact of risk gene overexpression on dendritic arborization and axon length in neurons was also examined. STUDY RESULTS: Our PWAS identified 42 proteins associated with SCZ and 14 with BD-I, among which NEK4, HARS2, SUGP1, and DUS2 were common to both conditions. TWAS and MR analysis verified the significant risk gene NEK4 for both SCZ and BD-I. PleioFDR analysis further supported genetic risk loci associated with NEK4 for both conditions. The cell-type specificity analysis revealed that NEK4 is expressed on the surface of glutamatergic neurons, and its overexpression enhances dendritic arborization and axon length in cultured primary neurons. CONCLUSIONS: These findings underscore a shared genetic origin for SCZ and BD-I, offering novel insights for potential therapeutic target identification.

Mitochondrial structure and function: A new direction for the targeted treatment of chronic liver disease with Chinese herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive fat accumulation, biological clock dysregulation, viral infections, and sustained inflammatory responses can lead to liver inflammation, fibrosis, and cancer, thus promoting the development of chronic liver disease. A comprehensive understanding of the etiological factors leading to chronic liver disease and the intrinsic mechanisms influencing its onset and progression can aid in identifying potential targets for targeted therapy. Mitochondria, as key organelles that maintain the metabolic homeostasis of the liver, provide an important foundation for exploring therapeutic targets for chronic liver disease. Recent studies have shown that active ingredients in herbal medicines and their natural products can modulate chronic liver disease by influencing the structure and function of mitochondria. Therefore, studying how Chinese herbs target mitochondrial structure and function to treat chronic liver diseases is of great significance. AIM OF THE STUDY: Investigating the prospects of herbal medicine the Lens of chronic liver disease based on mitochondrial structure and function. MATERIALS AND METHODS: A computerized search of PubMed was conducted using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "botanicals, mitochondria and chronic liver disease".Data from the Web of Science and Science Direct databases were also included. The research findings regarding herbal medicines targeting mitochondrial structure and function for the treatment of chronic liver disease are summarized. RESULTS: A computerized search of PubMed using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "phytopharmaceuticals, mitochondria, and chronic liver disease", as well as the Web of Science and Science Direct databases was conducted to summarize information on studies of mitochondrial structure- and function-based Chinese herbal medicines for the treatment of chronic liver disease and to suggest that the effects of herbal medicines on mitochondrial division and fusion.The study suggested that there is much room for research on the influence of Chinese herbs on mitochondrial division and fusion. CONCLUSIONS: Targeting mitochondrial structure and function is crucial for herbal medicine to combat chronic liver disease.

Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

Development and application of machine learning models for prediction of soil available cadmium based on soil properties and climate features.

Identifying the key influencing factors in soil available cadmium (Cd) is crucial for preventing the Cd accumulation in the food chain. However, current experimental methods and traditional prediction models for assessing available Cd are time-consuming and ineffective. In this study, machine learning (ML) models were developed to investigate the intricate interactions among soil properties, climate features, and available Cd, aiming to identify the key influencing factors. The optimal model was obtained through a combination of stratified sampling, Bayesian optimization, and 10-fold cross-validation. It was further explained through the utilization of permutation feature importance, 2D partial dependence plot, and 3D interaction plot. The findings revealed that pH, surface pressure, sensible heat net flux and organic matter content significantly influenced the Cd accumulation in the soil. By utilizing historical soil surveys and climate change data from China, this study predicted the spatial distribution trend of available Cd in the Chinese region, highlighting the primary areas with heightened Cd activity. These areas were primarily located in the eastern, southern, central, and northeastern China. This study introduces a novel methodology for comprehending the process of available Cd accumulation in soil. Furthermore, it provides recommendations and directions for the remediation and control of soil Cd pollution.

Identification of symptom clusters and sentinel symptoms during the first cycle of chemotherapy in patients with lung cancer.

PURPOSE: To identify symptom clusters (SCs) in patients with lung cancer who are undergoing initial chemotherapy and to identify the sentinel symptoms of each SC. METHODS: A convenience sampling method was used to recruit patients with lung cancer who were undergoing their initial chemotherapy treatment. Patient information was collected using the General Demographic Questionnaire, MD Anderson Symptom Inventory (including the lung cancer module) and a schedule documenting the initial occurrence of symptoms. The Walktrap algorithm was employed to identify SCs, while sentinel symptoms within each SC were identified using the Apriori algorithm in conjunction with the initial occurrence time of symptoms. RESULTS: A total of 169 patients with lung cancer participated in this study, and four SCs were identified: the psychological SC (difficulty remembering, sadness, dry mouth, numbness or tingling, and distress), somatic SC (pain, fatigue, sleep disturbance, and drowsiness), respiratory SC (coughing, expectoration, chest tightness, and shortness of breath), and digestive SC (nausea, poor appetite, constipation, vomiting, and weight loss). Sadness, fatigue, and coughing were identified as sentinel symptoms of the psychological, somatic, and respiratory SCs, respectively. However, no sentinel symptom was identified for the digestive SC. CONCLUSION: Patients with lung cancer who are undergoing chemotherapy encounter a spectrum of symptoms, often presenting as SCs. The sentinel symptom of each SC emerges earlier than the other symptoms and is characterized by its sensitivity, significance, and driving force. It serves as a vital indicator of the SC and assumes a sentry role. Targeting sentinel symptoms might be a promising strategy for determining the optimal timing of interventions and for mitigating or decelerating the progression of the other symptoms within the SC.

Exploring Central and Bridge Symptoms in Patients with Lung Cancer: A Network Analysis.

OBJECTIVES: This study aimed to identify symptom clusters in lung cancer patients undergoing chemotherapy and the central and bridge symptoms within each symptom cluster. METHODS: In this cross-sectional study, 1,255 patients with lung cancer were recruited through convenience sampling at Nanfang Hospital. Patient symptom burden was assessed using the M.D. Anderson Symptom Inventory (MDASI) and the Lung Cancer module of the MDASI (MDASI-LC). Symptom clusters were identified using the Walktrap algorithm, and central and bridge symptoms in the symptom clusters were identified by network analysis. RESULTS: The patients included 818 (65.18%) males and 437 (34.82%) females with a mean age of 56.56 ± 11.78 years. Four symptom clusters were identified: fatigue, gastrointestinal, psychoneurological and respiratory. Their central symptoms were fatigue, vomiting, distress and hemoptysis, respectively, and their bridge symptoms were pain, vomiting, dry mouth and shortness of breath. CONCLUSIONS: Lung cancer symptoms show certain strong correlations with each other, resulting in symptom clusters. Central symptoms may influence other symptoms within a symptom cluster, and bridge symptoms might impact the density of the symptom network. This study identified central and bridge symptoms in lung cancer patients undergoing chemotherapy. Targeting these symptoms with interventions for symptom clusters could make symptom management more precise and effective. IMPLICATIONS FOR NURSING PRACTICE: In clinical settings, the burden of symptom clusters may be reduced by intervening against the central symptoms of these symptom clusters. Alternatively, if the objective is to diminish the connections between different symptom clusters and holistically alleviate the overall burden, interventions focused on bridge symptoms may be employed.

Passive green space exposure leading to lower aggression: The mediating role of sense of control.

Green spaces, integral to natural environments, have been extensively studied for their positive impact on mental health, yet their influence on social behavior, particularly aggression, is less explored. While prior research has predominantly emphasized the effects of actively engaging with nature, the significant role of passive nature exposure-a more common daily occurrence-has often been overlooked. We conducted two studies to explore the influence of passive green space exposure on aggression and the mediating effect of the sense of control. Study 1 (N = 240) utilized a cross-sectional survey to assess the relationship between passive green space exposure, sense of control, and aggression. Study 2 (N = 260) employed a single-factor between-subjects experimental design to further explore these relationships in a controlled environment. The results from both studies indicated that passive green space exposure is negatively related to aggression, and that this relationship is partially mediated by an increased sense of control. Specifically, passive green space exposure was found to negatively predict aggression by bolstering individuals' sense of control. These findings underscore the potential of enhancing the sense of control through environmental factors like green spaces as an effective strategy to reduce aggression. This study enriches our understanding of the broader impacts of green spaces, extending beyond mental health to include social behaviors. We discussed both the theoretical and practical implications of our findings, highlighting how urban planning and environmental design can incorporate green spaces to foster community well-being and mitigate aggressive behaviors.

Preparation and characterization of amphiphilic, biodegradable, waterborne polyurethanes without using organic solvent and catalyst.

Traditionally, waterborne polyurethanes (WPUs) are prepared using toxic organic solvents and catalysts. These WPUs are non-biodegradable and are buried or incinerated after the expiration date. This has adverse effects on the environment and human health, which limits the applications of WPUs. Herein, a special synthetic method was developed for biodegradable waterborne polyurethane (BWPU) by adding hydrophilic prepolymers into WPU prepolymers without using organic solvents and catalysts. Different proportions of polyethylene glycol (PEG) were introduced into polycaprolactone (PCL)-based BWPUs to improve the comprehensive properties. Results showed that as the PEG content was increased from 0 to 16 wt%, the solid content of BWPU increased from 34.8 wt% to 53.1 wt%, while the tensile strength and Young's modulus of BWPU films increased from 21.81 MPa to 56.83 MPa and 8.08 MPa to 19.4 MPa, respectively. However, the elongation at break did not decrease significantly, but still reached 827.17%. With an increase in PEG content, the crystallinity and phase separation decreased, while the hydrophilicity and surface energy increased for BWPU films. In addition, the prepared BWPUs had good biodegradability in PBS/lipase solution. The mass loss of BWPU without PEG reached 6.3 wt% after 4 weeks of degradation, whereas the mass losses of BWPUs with PEG reached 2.3-4.3 wt%. Obviously, the introduction of PEG did not increase biodegradability. Thus, the higher the PCL content, the faster the biodegradation rate. This work would provide an effective method for the preparation of ecofriendly biodegradable BWPU with excellent comprehensive properties.

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters.

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

Parallel Cerebrospinal Fluid and Serum Temporal Profile Assessment of Axonal Injury Biomarkers Neurofilament-Light Chain and Phosphorylated Neurofilament-Heavy Chain: Associations With Patient Outcome in Moderate-Severe Traumatic Brain Injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n = 277 unique subjects) and CSF (n = 95 unique subjects) daily for 1 week, and serum every 2 weeks for 6 months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n = 99 unique subjects) and CSF (n = 54 unique subjects) NF-L and pNF-H levels were measured at least daily during Days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r = 0.44-0.48; p < 0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (Months [M]2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p < 0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p < 0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and Glasgow Coma Scale. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

Whole-Genome Sequencing-Based Confirmatory Methods on RT-qPCR Results for the Detection of Foodborne Viruses in Frozen Berries.

Accurate detection, identification, and subsequent confirmation of pathogens causing foodborne illness are essential for the prevention and investigation of foodborne outbreaks. This is particularly true when the causative agent is an enteric virus that has a very low infectious dose and is likely to be present at or near the limit of detection. In this study, whole-genome sequencing (WGS) was combined with either of two non-targeted pre-amplification methods (SPIA and SISPA) to investigate their utility as a confirmatory method for RT-qPCR positive results of foods contaminated with enteric viruses. Frozen berries (raspberries, strawberries, and blackberries) were chosen as the food matrix of interest due to their association with numerous outbreaks of foodborne illness. The hepatitis A virus (HAV) and human norovirus (HuNoV) were used as the contaminating agents. The non-targeted WGS strategy employed in this study could detect and confirm HuNoV and HAV at genomic copy numbers in the single digit range, and in a few cases, identified viruses present in samples that had been found negative by RT-qPCR analyses. However, some RT-qPCR-positive samples could not be confirmed using the WGS method, and in cases with very high Ct values, only a few viral reads and short sequences were recovered from the samples. WGS techniques show great potential for confirmation and identification of virally contaminated food items. The approaches described here should be further optimized for routine application to confirm the viral contamination in berries.