An abrupt regime shift of bacterioplankton community from weak to strong thermal pollution in a subtropical bay.

Thermal pollution from the cooling system of the nuclear power plants greatly changes the environmental and the ecological conditions of the receiving marine water body, but we know little about their impact on the steady-state transition of marine bacterioplankton communities. In this study, we used high-throughput sequencing based on the 16S rRNA gene to investigate the impact of the thermal pollution on the bacterioplankton communities in a subtropical bay (the Daya Bay). We observed that thermal pollution from the cooling system of the nuclear power plant caused a pronounced thermal gradient ranging from 19.6°C to 24.12°C over the whole Daya Bay. A temperature difference of 4.5°C between the northern and southern parts of the bay led to a regime shift in the bacterioplankton community structure. In the three typical scenarios of regime shifts, the steady-state transition of bacterioplankton community structure in response to temperature increasing was more likely consistent with an abrupt regime shift rather than a smooth regime or a discontinuous regime model. Water temperature was a decisive factor on the regime shift of bacterioplankton community structure. High temperature significantly decreased bacterioplankton diversity and shifted its community compositions. Cyanobium and Synechococcus of Cyanobacteria, NS5 marine group of Bacteroidota, and Vibrio of Gammaproteobacteria were found that favored high temperature environments. Furthermore, the increased water temperature significantly altered the community assembly of bacterioplankton in Daya Bay, with a substantial decrease in the proportion of drift and others, and a marked increase in the proportion of homogeneous selection. In summary, we proposed that seawater temperature increasing induced by the thermal pollution resulted in an abrupt regime shift of bacterioplankton community in winter subtropical bay. Our research might broad our understanding of marine microbial ecology under future conditions of global warming.

Mechanism for improving the in vitro digestive properties of coconut milk by modifying the structure and properties of coconut proteins with monosodium glutamate.

In this paper, the effect of monosodium glutamate (MSG) on coconut protein (CP) solubility, surface hydrophobicity, emulsification activity, ultraviolet spectroscopy and fluorescence spectroscopy was investigated. Meanwhile, the changes in the in vitro digestive properties of coconut milk were also further analyzed. MSG treatment altered the solubility and surface hydrophobicity of CP, thereby improving protein digestibility. Molecular docking showed that CP bound to pepsin and trypsin mainly through hydrogen bonds and salt bridges. And MSG increased the cleavable sites of pepsin and trypsin on CP, thus further improving the protein digestibility. In addition, MSG increased the Na+ concentration in coconut milk, promoted flocculation and aggregation between coconut milk droplets, which prevented the binding of lipase and oil droplets and inhibited lipid digestion. These findings may provide new ideas and insights to improve the digestive properties of plant-based milk.

Intratumor microbiome-derived butyrate promotes lung cancer metastasis.

Most recurrences of lung cancer (LC) occur within 3 years after surgery, but the underlying mechanism remains unclear. Here, we collect LC tissues with shorter (<3 years, recurrence group) and longer (>3 years, non-recurrence group) recurrence-free survival. By using 16S sequencing, we find that intratumor microbiome diversity is lower in the recurrence group and butyrate-producing bacteria are enriched in the recurrence group. The intratumor microbiome signature and circulating microbiome DNA can accurately predict LC recurrence. We prove that intratumor injection of butyrate-producing bacteria Roseburia can promote subcutaneous tumor growth. Mechanistically, bacteria-derived butyrate promotes LC metastasis by increasing expression of H19 in tumor cells through inhibiting HDAC2 and increasing H3K27 acetylation at the H19 promoter and inducing M2 macrophage polarization. Depletion of macrophages partially abolishes the metastasis-promoting effect of butyrate. Our results provide evidence for the cross-talk between the intratumor microbiome and LC metastasis and suggest the potential prognostic and therapeutic value of the intratumor microbiome.

Circulating microbiome DNA as biomarkers for early diagnosis and recurrence of lung cancer.

Lung cancer mortality is exacerbated by late-stage diagnosis. Emerging evidence indicates the potential clinical significance of distinct microbial signatures as diagnostic and prognostic biomarkers across various cancers. However, circulating microbiome DNA (cmDNA) profiles are underexplored in lung cancer (LC). Here, whole-genome sequencing is performed on plasma of LC patients and healthy controls (HCs). Differentially enriched microbial species are identified between LC and HC. A diagnostic model is developed, which has a high sensitivity of 87.7% and achieves an AUC of 93.2% in the independent validation dataset. Crucially, this model demonstrates the capability to detect early-stage LC, achieving a sensitivity of 86.5% for stage I and 87.1% for tumors <1 cm. In addition, we construct a cmDNA model for recurrence, which precisely predicts LC recurrence after surgery. Overall, this study highlights the significant alterations of cmDNA profiles in LC, indicating its potential as biomarkers for early diagnosis and recurrence.

Effect of borax-modified activator on mechanical properties and drying shrinkage of alkali-activated slag/metakaolin mortar.

Alkali-activated materials (AAMs) possess several advantages, such as high strengths and low carbon emissions. However, their application is hindered due to their significant shrinkage. This study explored the effect of borax-modified sodium silicate activator and metakaolin (MK) on the mechanical properties and drying shrinkage (DS) of alkali-activated slag (AAS) and AAS/MK (AASM) mortars. X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to characterize the hydration products. The results showed that the DS reduction of the AAS mortar was related to decreased Na2O content, a reduction in the proportion of mesopores, and the formation of moisture-retaining borate compounds. The DS reduction of the AASM mortar was attributed to the ultra-fine differential effect induced by MK, reducing the connected pores. The modified activator combined with MK increased the chemically bound water content in the matrix. Additionally, the B-O bond and highly active MK improved compactness of the AASM mortar. The use of borax-modified activators and MK provides a new solution to address the significant shrinkage issue in AAMs. This sets the stage for AAMs to potentially replace OPC, contributing to low-carbon emissions and promoting environmental protection.

Add-on effects of Chinese herbal medicine external application (FZHFZY) to topical urea for mild-to-moderate psoriasis vulgaris: Protocol for a double-blinded randomized controlled pilot trial embedded with a qualitative study.

Psoriasis vulgaris is a chronic dermatological disease with a high global prevalence. It significantly reduces patients' quality of life and is associated with a substantial economic burden. Conventional therapies for mild-to-moderate psoriasis are often associated with insufficient long-term symptomatic relief and side effects. Chinese herbal medicine (CHM) is commonly used for psoriasis management. A CHM formula, namely Fu zheng he fu zhi yang (FZHFZY), has shown promising treatment effects in clinical practice when used as a bath therapy. However, its efficacy and safety has not been evaluated by a rigorous randomized controlled trial (RCT). Therefore, we designed a double-blinded pilot RCT embedded with a qualitative study on CHM formula FZHFZY plus topical urea for mild-to-moderate psoriasis vulgaris to advance the evidence development and practice of CHM external application for psoriasis. This will be a mixed-method design consisting of a pilot RCT and a qualitative study. The pilot RCT is a two-arm, parallel, placebo-controlled, double-blinded trial. Sixty eligible participants will be randomized at a 1:1 ratio to receive eight weeks' treatment of either FZHFZY plus 10% urea cream, or placebo plus 10% urea cream, with 12-week follow-up visits after the treatment phase. The CHM or placebo will be administered externally as a bath therapy. Outcome measures include trial feasibility, efficacy and safety. The primary efficacy outcome will be Psoriasis Area Severity Index (PASI). Secondary efficacy outcomes include Physician Global Assessment, PASI-75, PASI-50, Body Surface Area, Dermatology Life Quality Index, Skindex-16, itch visual analogue scale and relapse. The qualitative study will be conducted to collect participants' feedback on CHM external application and their experience with the pilot RCT. This study will advance the evidence-based clinical practice of using CHM for psoriasis vulgaris and then to support translation of findings into clinical practice in the future. Trial registration number: ChiCTR2200064092.

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study.

Objective: To explore the influence of serum metabolites on the risk of psoriasis. Methods: In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio's odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran's Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages. Results: In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism. Conclusion: Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

Adding Chinese herbal medicine bath therapy to conventional therapies for psoriasis vulgaris: A systematic review with meta-analysis of randomised controlled trials.

BACKGROUND: Chinese herbal medicine (CHM) bath is commonly used in China as an adjuvant therapy for managing psoriasis vulgaris. Previous systematic reviews showed that CHM bath therapy was effective and safe for psoriasis vulgaris, however, without exploration of the specifics of CHM bath therapy such as the optimal temperature, duration of each session, and the total treatment duration. PURPOSE: To evaluate the add-on effects of CHM bath therapy to conventional therapies for adult psoriasis vulgaris. METHODS: We conducted a comprehensive search in nine medical databases from inception to September 2022 to identify relevant randomised controlled trials (RCTs) published in Chinese or English. The included studies compared the combination of CHM bath therapy and conventional therapies to conventional therapies alone for adult psoriasis vulgaris. Methodological quality assessment of the included RCTs was performed using the Cochrane risk-of-bias tool 2 (RoB 2). Statistical analysis was carried out using RevMan 5.4, R 4.2.3 and Stata 12.0 software. The certainty of evidence of outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation Working Group (GRADE) system. RESULTS: A total of 23 RCTs involving 2,183 participants were included in this systematic review. Findings suggested that the combination of CHM bath therapy and conventional therapies was more effective in reducing Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and itch visual analogue scale, compared to using conventional therapies alone. These enhanced effects were notably observed when the CHM bath was set above 38 °C and had a duration of 20 and 30 min, as assessed by DLQI. Moreover, an eight-week treatment duration resulted in better effects for PASI compared to shorter durations. Additionally, the top ten frequently used herbs in the included studies were identified. Despite the findings, the certainty of evidence was rated as 'low' or 'moderate' based on the GRADE assessment, and significant heterogeneity was detected in subgroup and sensitivity analyses. CONCLUSION: The CHM bath therapy combined with conventional therapies is more effective and safer than conventional therapies alone for adult psoriasis vulgaris. The results suggest a potential correlation between treatment effects and factors such as extended treatment duration, increased bath temperature, and longer bath sessions. However, the certainty of evidence was downgraded due to methodological limitations of the included studies. To confirm the findings of this systematic review, a double-blinded, placebo-controlled RCT is needed in the future.

Network pharmacology and gut microbiota insights: unraveling Shenling Baizhu powder's role in psoriasis treatment.

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood. Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models. Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1ß, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement. Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP's modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

Non-Woven Fabric Thermal-Conductive Triboelectric Nanogenerator via Compositing Zirconium Boride.

With the vigorous development of the Internet of Things, 5G technology, and artificial intelligence, flexible wearable sensors have received great attention. As a simple and low-cost power supply in wearable sensors, the triboelectric nanogenerator (TENG) has a wide range of applications in the field of flexible electronics. However, most polymers are thermally poor conductors (less than 0.1 W/(m·K)), resulting in insufficient heat dissipation performance and limiting the development of TENG. In this study, a high-performance non-woven fabric TENG with strong thermal conductivity (0.26 W/m·K) was achieved by introducing ZrB2 into the polyurethane (PU) matrix. The excellent output performance with an open circuit voltage (Voc) of 347.6 V, a short circuit current (Isc) of 3.61 µA, and an accumulated charge of 142.4 nC endows it with good sensitivity. The electrospun PU/ZrB2 composites exhibit excellent sensing performance to detect body movements in situ, such as pressing, clapping, running, and walking. Moreover, the generated power can light up 224 LED bulbs as a demonstration of self-powering ability.

Efficacy and Safety Analysis of Emergency Endoscopic Self-Expanding Metal Stent Placement Without Fluoroscopic Assistance for Right-Sided Colonic Cancer Obstruction.

BACKGROUND: Traditionally, surgical treatment is recommended for right-sided colonic cancer obstruction (RCCO); however, the literature comparing surgical or non-surgical procedures is lacking. METHODS: Patients included in this study were divided into two groups: one group received elective surgery after self-expanding metal stent (SEMS) placement, i.e., the bridge to surgery (BTS) group, and one group received emergency surgery (ES). RESULTS: Thirty-five patients were included in the BTS group and 60 patients underwent ES. The technical and clinical success rates for SEMS placement were 100% and 88.6%, respectively, while the short-term complication rates were 51.4% and 33.3% for the BTS and ES groups, respectively (p = 0.082). Overall, 2.9% and 3.3% of postoperative deaths occurred in the BTS and ES groups (p = 1.000). The 1-year overall survival (OS) rates were 91.4% and 88.3% (p = 0.840), 3-year OS rates were 85.7% and 81.7% (p = 0.860), and 5-year OS rates were 82.9% and 76.7% (p = 0.620) in the BTS and ES groups, respectively. No tumor recurrence was found in the BTS group but seven recurrences were found in the ES group (11.7%) [p = 0.091]. Laparoscopic surgery was chosen by 42.9% of patients in the BTS group and 26.7% of patients in the ES group (p = 0.104); however, the length of hospital stay (p = 0.001) was longer in the BTS group. CONCLUSIONS: In the two groups, no differences were found in terms of postoperative complications and mortality as well as OS. The BTS group preferred to perform laparoscopic surgery and the technical success rate of stenting was high, therefore SEMS for RCCO was considered safe and feasible.

The organization-level and physician-level factors associated with primary care physicians' confidence in pandemic response: A multilevel study in China.

Primary care physicians (PCPs) suffered from heavy workloads and health problems during COVID-19 pandemics, and building their confidence in pandemic response has great potential to improve their well-being and work performance. We identified the organizational factors associated with their confidence in pandemic response and proposed potential management levers to guide primary care response for the pandemic. We conducted a cross-sectional survey with 224 PCPs working in 38 community health centers in China. Guided by self-efficacy theory, organization-level factors (organizational structure and organizational culture) and physician-level factors (job skill variety, perceived organizational support, work-family conflict, and professional fulfillment) were selected, and two-level ordinal logit models were built to examine their association with PCPs' confidence in pandemic response. We found that hierarchical culture (OR = 3.51, P<0.05), perceived organizational support (OR = 2.36, P<0.05), job skill variety (OR = 1.86, P<0.05), and professional fulfillment (OR = 2.26, P<0.05) were positively associated with PCPs' confidence in pandemic response. However, the influence of organization structure and work-family conflict seemed limited. The study not only increases our understanding of the influence of organizational context on PCPs' pandemic response confidence, but also points out potential management levers for front-line primary care managers to enhance primary care pandemic response capacity.

Molecular mechanisms of macrophage immunomodulation mediated by Areca inflorescence polysaccharides based on RNA-seq analysis.

The elucidation of the immunomodulatory molecular mechanisms of polysaccharides has contributed to their further development and application. In this study, the effect of Areca inflorescence polysaccharide (AFP2a) on macrophage activation was confirmed and the detailed mechanisms were investigated based on a comprehensive transcriptional study and specific inhibitors. The results showed that AFP2a induced macrophage activation (M1 polarization), promoting macrophage proliferation, reactive oxygen species production, nitric oxide and cytokine release, and costimulatory molecule expression. RNA-seq analysis identified 5919 differentially expressed genes (DEGs). For DEGs, GO, KEGG, and Reactome enrichment analyses and PPI networks were conducted, elucidating that AFP2a activated macrophages mainly by triggering the Toll-like receptor cascade and corresponding adapter proteins (TIRAP and TRIF), thereby resulting in downstream NF-κB, TNF, and JAK-STAT signaling pathway expression. The inhibition assay revealed that TLR4 and TLR2 were essential for the recognition of AFP2a. This work provides an in-depth understanding of the immunoregulatory mechanism of AFP2a while offering a molecular basis for AFP2a to serve as a potential natural immunomodulator.

Interfacial Behavior and Long-Term Stability of the Emulsions Stabilized by Sugar Beet Pectin-Ca2+ Complexes with Different Cross-Linking Degrees.

Recent studies showed that sugar beet pectin exhibited more excellent emulsifying properties than traditional citrus peel pectin and apple pectin ascribed to the higher content of neutral sugar, protein, ferulic acid, and acetyl groups. It is precisely because of the extremely complex molecular structure of pectin that the emulsifying properties of the pectin-Ca2+ complex are still unclear. In this study, SBP-Ca2+ complexes with different cross-linking degrees were prepared. Subsequently, their interfacial adsorption kinetics, the resistance of interfacial films to external perturbances, and the long-term stability of the emulsions formed by these SBP-Ca2+ complexes were measured. The results indicated that the highly cross-linked SBP-Ca2+ complex exhibited slower interfacial adsorption kinetics than SBP alone. Moreover, compared with SBP alone, the oil-water interfacial film loaded by the highly cross-linked SBP-Ca2+ complex exhibited a lower elasticity and a poorer resistance to external perturbances. This resulted in a larger droplet size, a lower ζ-potential value, a larger continuous viscosity, and a worse long-term stability of the emulsion formed by the highly cross-linked SBP-Ca2+ complex. This study has very important guiding significance for deeply understanding the emulsification mechanism of the pectin-Ca2+ complex.

Photocatalytic inactivation mechanism of nano-BiPO4 against Vibrio parahaemolyticus and its application in abalone.

Vibrio parahaemolyticus (V. parahaemolyticus) is the main pathogenic bacteria in seafood that can cause serious food-borne illness. The annual incidence of V. parahaemolyticus infection in the United States exceeds 45,000 cases, indicating there are potential shortcomings in seafood sterilization techniques. Meanwhile, the ongoing emergence of antibiotic-resistant strains highlights the urgent need for novel bacteriostatic strategies to eliminate V. parahaemolyticus. Nano-BiPO4 is a semiconductor with high H2O2 production efficiency and has potential for photocatalytic bacterial inactivation. But the effectiveness and mechanism of BiPO4 photocatalytic inactivation of V. parahaemolyticus has not been reported. In this study, nano-BiPO4 synthesized in pure water (P1) was found to exhibit optimal H2O2 production efficiency (1203 µmol h-1g-1) and antibacterial activity (in 0.8 g/L). Under UV light irradiation, P1 induced alterations in bacterial cell morphology, elevation in intracellular levels of ROS, H2O2, O2-, GSSG and MDA, and reduction in GSH level. Meanwhile, metabolomic analysis revealed that P1 stimulates the arginine biosynthesis, TCA cycle and alanine, aspartate and glutamate metabolism. These abnormal changes in the oxidative stress indicators and metabolic pathways proved that the bacterial damage was related to the H2O2 produced by nano-BiPO4 photocatalysis. Moreover, sliced abalone and hemolysis assay were used to demonstrate the applicability and biosafety of P1. This study provides theoretical support for exploring nano-BiPO4 as a bacterial inhibitor against V. parahaemolyticus.

A bibliometrics study on the status quo and hot topics of pathogenesis of psoriasis based on Web of Science.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Great progress has been made in the pathogenesis of psoriasis in recent years, but there is no bibliometric study on the pathogenesis of psoriasis. The purpose of this study was to use bibliometrics method to analyze the research overview and hot spots of pathogenesis of psoriasis in recent 10 years, so as to further understand the development trend and frontier of this field. METHODS: The core literatures on the pathogenesis of psoriasis were searched in the Web of Science database, and analyzed by VOSviewer, CiteSpace, and Bibliometrix in terms of the annual publication volume, country, institution, author, journal, keywords, and so on. RESULTS: A total of 3570 literatures were included. China and the United States were the main research countries in this field, and Rockefeller University was the main research institution. Krueger JG, the author, had the highest number of publications and the greatest influence, and Boehncke (2015) was the most cited local literature. J INVEST DERMATOL takes the top spot in terms of the number of Dermatol articles and citation frequency. The main research hotspots in the pathogenesis of psoriasis are as follows: (1) The interaction between innate and adaptive immunity and the related inflammatory loop dominated by Th17 cells and IL-23/IL-17 axis are still the key mechanisms of psoriasis; (2) molecular genetic studies represented by Long Non-Coding RNA (LncRNA); (3) integrated research of multi-omics techniques represented by gut microbiota; and (4) Exploring the comorbidity mechanism of psoriasis represented by Metabolic Syndrome (MetS). CONCLUSION: This study is a summary of the current research status and hot trend of the pathogenesis of psoriasis, which will provide some reference for the scholars studying the pathogenesis of psoriasis.

Characterization and emulsifying ability evaluation of whey protein-pectin conjugates formed by glycosylation.

Glycosylation is a method that enhances the functional properties of proteins by covalently attaching sugars to them. This study aimed at preparing three conjugates (WP-HG, WP-SBP, and WP-RGI) by dry heating method to research the influence of different pectin structures on the functional properties of WP and characterize properties and structures of these conjugates. The research results manifested that the degree of glycosylation (DG) of HG, SBP and RGI were 13.13 % ± 0.07 %, 23.27 % ± 0.3 % and 36.39 % ± 0.3 % respectively, suggesting that the increase of the number of branch chains promoted the glycosylation reaction. The formation of the conjugate was identified by the FT-IR spectroscopy technique. And SEM showed that WP could covalently bind to pectin, resulting in a smoother and denser surface of the conjugates. The circular dichroism analysis exhibited that the glycosylation reaction altered the secondary structure of WP and decreased the α-Helix content. This structural change in the protein spatial conformation led to a decrease in the hydrophobicity of protein surface. But the addition of pectin further regulated the hydrophilic-hydrophobic ratio on the surface of the protein, thus improving the emulsification properties of WP. In addition, the glycosylation could improve the stability of the emulsion, giving it a smaller droplet size, higher Zeta-potential and more stable properties. In a word, this study pointed out the direction for the application of different pectin structures in the development of functional properties of glycosylation products in food ingredients.

Plasma cell-free DNA as a sensitive biomarker for multi-cancer detection and immunotherapy outcomes prediction.

BACKGROUND: Cell-free DNA (cfDNA) has shown promise in detecting various cancers, but the diagnostic performance of cfDNA end motifs for multiple cancer types requires verification. This study aimed to assess the utility of cfDNA end motifs for multi-cancer detection. METHODS: This study included 206 participants: 106 individuals with cancer, representing 20 cancer types, and 100 healthy individuals. The participants were divided into training and testing cohorts. All plasma cfDNA samples were profiled by whole-genome sequencing. A random forest model was constructed using cfDNA 4 bp-end-motif profiles to predict cancer in the training cohort, and its performance was evaluated in the testing cohort. Additionally, a separate random forest model was developed to predict immunotherapy responses. RESULTS: In the training cohort, the model based on 4 bp-end-motif profiles achieved an AUC of 0.962 (95% CI 0.936-0.987). The AUC in the testing cohort was 0.983 (95% CI 0.960-1.000). The model also maintained excellent predictive ability in different tumor sub-cohorts, including lung cancer (AUC 0.918, 95% CI 0.862-0.974), gastrointestinal cancer (AUC 0.966, 95% CI 0.938-0.993), and other cancer cohort (AUC 0.859, 95% CI 0.776-0.942). Moreover, the model utilizing 4 bp-end-motif profiles exhibited sensitivity in identifying responders to immunotherapy (AUC 0.784, 95% CI 0.609-0.960). CONCLUSION: The model based on 4 bp-end-motif profiles demonstrates superior sensitivity in multi-cancer detection. Detection of 4 bp-end-motif profiles may serve as potential predictive biomarkers for cancer immunotherapy.

Multi-omics analysis reveals NNMT as a master metabolic regulator of metastasis in esophageal squamous cell carcinoma.

Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial-mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.