Characteristics of humification, functional enzymes and bacterial community metabolism during manganese dioxide-added composting of municipal sludge.

The aim of this study was to assess effects of MnO2 addition (CK-0%, T1-2% and T2-5%) on humification and bacterial community during municipal sludge (MS) composting. The results suggested that MnO2 addition inhibited the growth of Nitrospira but stimulated Nonomuraea, Actinomadura, Streptomyces and Thermopolyspora, facilitating the lignocellulose degradation and humification with the increase in organic matter degradation by 13.8%-19.2% and humic acid content by 10.9%-20.6%. Compared to CK, the abundances of exoglucanase (EC:3.2.1.91), endo-1,4-beta-xylanase (EC:3.2.1.136) and endomannanase (EC:3.2.1.78) increased by 88-99, 52-66 and 4-15 folds, respectively. However, 5%-MnO2 induced the enrichment of Mizugakiibacter that harms the environment of agricultural production. The addition of 2%-MnO2 was recommended for MS composting. Furthermore, metabolic function analysis indicated that MnO2 addition altered amino acid and carbohydrate metabolism, especially enhancing propanoate metabolism and butanoate metabolism but inhibiting citrate cycle. Structural equation modeling revealed that Nonomuraea and Actinomadura were the main drivers for lignocellulose degradation. This study provided theoretical guidance in regulating humification via MnO2 for MS composting.

How well global dietary intake estimates agree: a case of sodium consumption.

Global dietary data repositories are key components of nutrition surveillance. The two most comprehensive databases, the Global Dietary Database (GDD) and the Global Burden Disease (GBD), provide national dietary intake estimates but use different data sources and models to generate estimates. To explore the agreement between GDD and GBD estimates, we compared country-specific average daily sodium intakes in 169 countries over a 28-year period using descriptive statistics, the Bland-Altman method, and prevalence exceeding the intake reference level of 2.3 g/day. We detected a staggering 36% difference between GDD and GBD estimates of global mean intakes (2.68 ± 0.74 vs. 3.88 ± 1.15 g/day, respectively; p < 0.0001). As 104 (61.5%) countries reported to have over-consumed sodium by both databases, the development of standardized approaches for national dietary intake estimation is critical for monitoring global sodium intake in a systematic and comprehensive way and for implementing global strategies to reduce sodium intake.

Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library.

Nanobodies have emerged as promising tools in biomedicine due to their single-chain structure and inherent stability. They generally have convex paratopes, which potentially prefer different epitope sites in an antigen compared to traditional antibodies. In this study, a synthetic phage display nanobody library was constructed and used to identify nanobodies targeting a tumor-associated antigen, the human B7-H3 protein. Combining next-generation sequencing and single-clone validation, two nanobodies were identified to specifically bind B7-H3 with medium nanomolar affinities. Further characterization revealed that these two clones targeted a different epitope compared to known B7-H3-specific antibodies, which have been explored in clinical trials. Furthermore, one of the clones, dubbed as A6, exhibited potent antibody-dependent cell-mediated cytotoxicity (ADCC) against a colorectal cancer cell line with an EC50 of 0.67 nM, upon conversion to an Fc-enhanced IgG format. These findings underscore a cost-effective strategy that bypasses the lengthy immunization process, offering potential rapid access to nanobodies targeting unexplored antigenic sites.

Weight Loss Trajectories and Short-Term Prediction in an Online Weight Management Program.

The extent to which early weight loss in behavioral weight control interventions predicts long-term success remains unclear. In this study, we developed an algorithm aimed at classifying weight change trajectories and examined its ability to predict long-term weight loss based on weight early change. We utilized data from 667 de-identified individuals who participated in a commercial weight loss program (Instinct Health Science), comprising 69,363 weight records. Sequential polynomial regression models were employed to classify participants into distinct weight trajectory patterns based on key model parameters. Next, we applied multinomial logistic models to evaluate if early weight loss in the first 14 days and prolonged duration of participation were significantly associated with long-term weight loss patterns. The mean percentage of weight loss was 7.9 ± 5.1% over 133 ± 69 days. Our analysis revealed four main weight loss trajectory patterns: a steady decrease over time (30.6%), a decrease to a plateau with subsequent decline (15.8%), a decrease to a plateau with subsequent increase (46.9%), and no substantial decrease (6.7%). Early weight change rate and total participating duration emerged as significant factors in differentiating long-term weight loss patterns. These findings contribute to support the provision of tailored advice in the early phase of behavioral interventions for weight loss.

Characterization of the MIKCC-type MADS-box gene family in blueberry and its possible mechanism for regulating flowering in response to the chilling requirement.

MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.

Exposure and Health Risk Assessment of Heavy Metal in Crayfish from the Middle and Lower Reaches of the Yangtze River.

Red swamp crayfish (Procambarus clarkia) is an exposed species to heavy metals due to their lifestyle of direct contact with sediments. Based on the complete crayfish industry, we focus on the presence of heavy metals in crayfish from different circulation links, which provides a new idea for the investigation of heavy metals in food. To analyze the exposure levels of heavy metals in crayfish during aquaculture and circulation, the five elements (Cd, Pb, Hg, Cr, Cu) in crayfish from 126 sampling sites were investigated. Cultured environmental samples were collected for Spearman correlation analysis. Monte Carlo simulation was used to analyze the uncertain health risks of heavy metals in crayfish. The results indicated that the average heavy metal concentrations in crayfish were all below the limit threshold values. The hepatopancreas was the main target organ for heavy metal accumulation (Cd: 0.3132 mg/kg; Pb: 0.0258 mg/kg; Hg: 0.0072 mg/kg; Cr: 0.1720 mg/kg; Cu: 10.6816 mg/kg). The positive correlation of heavy metal content between crayfish and sediments was not significant under the crayfish-rice coculture model. The 95th HI values for adults and children ranged from 0.022 to 0.042 and 0.071 to 0.137, well below 1, indicating that heavy metals do not pose a noncarcinogenic risk to humans. The potential carcinogenic risk of Cd and Cr in crayfish should be taken seriously, as the 95th CR values for children have reached 4.299 × 10-5 and 6.509 × 10-5, respectively.

Antibody-mediated spike activation promotes cell-cell transmission of SARS-CoV-2.

The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is strongly resistant to extracellular therapeutic and convalescent antibodies via an unknown mechanism. Here, we describe the antibody-mediated spike activation and syncytia formation on cells displaying the viral spike. We found that soluble antibodies against receptor binding motif (RBM) are capable of inducing the proteolytic processing of spike at both the S1/S2 and S2' cleavage sites, hence triggering ACE2-independent cell-cell fusion. Mechanistically, antibody-induced cell-cell fusion requires the shedding of S1 and exposure of the fusion peptide at the cell surface. By inhibiting S1/S2 proteolysis, we demonstrated that cell-cell fusion mediated by spike can be re-sensitized towards antibody neutralization in vitro. Lastly, we showed that cytopathic effect mediated by authentic SARS-CoV-2 infection remain unaffected by the addition of extracellular neutralization antibodies. Hence, these results unveil a novel mode of antibody evasion and provide insights for antibody selection and drug design strategies targeting the SARS-CoV-2 infected cells.

Whole genome sequencing in high-grade cervical intraepithelial neoplasia patients from different ethnic groups in China.

Cervical cancer (CC) is the fourth most common cancer in women worldwide. It develops through precancerous lesions (cervical intraepithelial neoplasia (CIN), graded from low-grade (CIN1) to high-grade (CIN2-3)). It is well established that precancerous and cancerous cervical lesions are caused by a persistent infection with high-risk types of the human papilloma virus (hrHPV). To have a deeper understanding of the pathogenesis of CIN and CC, we systematically analyzed the landscape of genomic alterations and HPV integration profiles in high-grade CIN2/3. We performed deep whole genome sequencing on exfoliated cervical cells and matched peripheral blood samples from a cohort of 51 Chinese patients (of whom 35 were HPV+) with high-grade CIN from 3 ethnic groups and constructed strict integrated workflow of genomic analysis. In addition, the HPV types and integration breakpoints in the exfoliated cervical cells from these patients were examined. Genomic analysis identified 6 significantly mutated genes (SMGs), including CDKN2A, PIK3CB, FAM20A, RABEP1, TMPRSS2 and SS18L1, in 51 CIN2/3 samples. As none of them had previously been identified as SMGs in the Cancer Genome Atlas cervical squamous cell carcinoma and endocervical adenocarcinoma (TCGA-CESC) cohort, future studies with larger sample size of CINs may be needed to validate our findings. Mutational signature analysis showed that mutational signatures of CINs were dramatically different from CCs, highlighting their different mutational processes and etiologies. Moreover, non-silent somatic mutations were detected in all of the CIN2/3 samples, and 88% of these mutations occurred in genes that also mutated in CCs of TCGA cohort. CIN2 samples had significantly less non-silent mutations than CIN3 samples (P = .0006). Gene ontology and pathway level analysis revealed that functions of mutated genes were significantly associated with tumorigenesis, thus these genes may be involved in the development and progression of CC. HPV integration breakpoints occurred in 28.6% of the CIN2/3 samples with HPV infection. Integrations of common high risk HPV types in CCs, including HPV16, 52, 58 and 68, also occurred in the CIN samples. Our results lay the groundwork for a deeper understanding of the molecular mechanisms underlying the pathogenesis of CC and pave the way for new tools for screening, diagnosis and treatment of cervical precancerous and cancerous lesions.

Geochemical behaviors of uranium and thorium during weathering and pedogenesis of carbonate rock: constraint from their speciation.

During weathering and pedogenesis of carbonate rock with poor-uranium (U) and thorium (Th), U and Th present the characteristics of strong leaching (especially U) and significant residual enrichment, the cause of which is still unclear. In this paper, a weathering profile developed by dolomite in karst area of Guizhou province in southwest China was selected, which showed zonation characteristics of bedrock (Y), powdery rock (Yf), and soil layer (T1 to T12) from the bottom to up. Through the determination of the occurrence speciation of U and Th in Y and weathering profile, combined with mineralogical, geochemical characteristics, and element mass balance calculation, the constraints of U and Th speciation on the geochemical behavior of U and Th during the weathering of carbonate rock were revealed. The results proved that U and Th in Y preferentially existed in acid insoluble phase, for example, the contents of U and Th in Y were 0.90 mg·kg-1 and 0.28 mg·kg-1, respectively, while those in acid insoluble matter were 2.34 mg·kg-1 and 2.57 mg·kg-1, respectively, but because the mass percentage of acid insoluble matter was extremely low (0.95%), the mass percentages of U and Th in the acid soluble phase in the whole rock were absolutely superior (96% of U and 86% Th). The U and Th in the acid soluble phase of Y were mainly adsorbed on the crystal surface of carbonate minerals or existed in the cement, and the U and Th in the carbonate lattice only accounted for a small proportion. From Y to Yf with the initial dissolution, U and Th released from the surface of carbonate minerals and cements were in carbonate-rich alkaline environment, and these portions of U and Th were leached out, resulting in strong loss of U and Th in the Yf (the loss rates are 83% of U and 65% of Th, respectively). From the Yf to the overlying soil layer T1, the carbonate components were completely dissolved, and the U and Th released from the carbonate lattice showed different behaviors, where U was completely leached and Th tended to stay in the weathered residue. Thus, in the soil layer T1 formed by Y or Yf , the residual U was the inheritance of the U in the acid insoluble phase of Y; For Th, it not only inherited the Th of acid insoluble phase of Y, but also superimposed the Th from carbonate lattice in Y. On the other hand, during the evolution process from Y to Yf and to soil layer T1, with the dissolution of carbonate, the acid insoluble phase also showed a significant tendency of chemical weathering. However, the U and Th in the Y acid insoluble phase were not leached with the decomposition of the acid insoluble phase but were redistributed among the residual phases. For the geochemical behaviors of U and Th in the evolution of soil profile (T1~T12), they were subjected to the occurrence speciation of U and Th in T1 and the change of U and Th occurrence speciation with the upward direction of soil profile. The U and Th released from the carrier minerals were mainly redistributed among the residual solid phases, which weakened the intensity of their further loss. This study deepens the understanding of the geochemical behavior of radionuclides in karst environment and provides reference for the treatment of radioactive pollution in karst areas.

Integrated immunological analysis of single-cell and bulky tissue transcriptomes reveals the role of interactions between M0 macrophages and naïve CD4+ T cells in the immunosuppressive microenvironment of cervical cancer.

In recent decades, the incidence and mortality of cervical cancer have declined in developed countries due to the implementation of screening and vaccination programs. However, cervical cancer remains one of the major culprits of cancer-related deaths in young women. Current studies have found that immune cell-related intercellular communication in the tumor microenvironment has a large impact on the construction of the immunosuppressive microenvironment. In this study, we performed a comprehensive immune analysis on bulk RNA-seq and scRNA-seq data obtained from cervical cancer and revealed that two highly plastic cell populations, M0 macrophages and naïve CD4+ T cells, were significantly correlated with prognosis and clinical phenotypes. Notably, signaling between M0 macrophages and naïve CD4+ T cells as well as intracellular transcription factor activity were significantly altered in the tumor state. Furthermore, we identified overlapping genes between the transcription factor target genes of M0 macrophages or naïve CD4+ T cells and the differentially expressed genes in each type of cell, and these overlapping genes were subsequently subjected to an analysis using the LASSO regression model. Finally, we generated a score index that was significantly associated with the clinical prognosis of cervical cancer. In conclusion, interventions to improve the communication between M0 macrophages and naïve CD4+ T cells may help to improve the immunosuppressive microenvironment of cervical cancer and prevent immune evasion. The relevant molecular mechanisms need to be further validated by experimental and cohort studies.

Heat-Denatured Lysozyme is a Novel Potential Non-alcoholic Disinfectant Against Respiratory Virus.

Respiratory diseases are significant recurrent threats to global public health. Since the 1918 Spanish flu pandemic, seasonal influenza viruses continue to cause epidemics around the world each year. More recently, the COVID-19 global pandemic conducted a public health crisis with more than 6 million deaths and it also severely affected the global economy. Due to the phenomenon that people get infection from objects carrying viruses, it has aroused people's attention to home disinfection. As there is no ideal existing common domestic disinfectant, new and safer antiviral disinfectants are urgently needed. Lysozyme is a natural antibacterial agent widespread in nature and widely used in healthcare and food industry because of is recognized safety. Recently, it has been shown that thermally denatured lysozyme has the ability to kill murine norovirus and hepatitis A virus. In our study, we also demonstrated that heat-denatured lysozyme (HDLz) had an antiviral effect against H1N1 influenza A virus, and we optimized its antiviral activities by testing different heating denaturation conditions, to generalize this property, using pseudotype virus neutralization assay, we found that HDLz can also inhibit the entry of H5N1, H5N6, and H7N1 avian influenza viruses as well as SARS-CoV and SARS-CoV-2 particles in cell with IC50 at the ng/mL range. Finally, using western blot analysis, we provide evidence that HDLz polymerization correlates with antiviral effect, which may be a precious possible quality control test. Altogether, our data support HDLz as a powerful anti-respiratory virus disinfectant as a sole or additive of current disinfectants to reduce concentration of toxic component.

Comparison of the molecular mechanisms of Fuzi Lizhong Pill and Huangqin decoction in the treatment of the cold and heat syndromes of ulcerative colitis based on network pharmacology.

OBJECTIVE: The aim of this study was to illuminate the similarities and differences of two prescriptions as "cold" and "heat" drugs for treating ulcerative colitis (UC) with the simultaneous occurrence of heat and cold syndrome via network pharmacology. METHODS: (1) Active compounds of Fuzi-Lizhong Pill (FLP) and Huangqin Decoction (HQT) were retrieved from the TCMSP database, and their common active compounds were compared using the Venn diagram. (2) Potential proteins targeted to three sets of compounds either (i) shared by FLP and HQT, (ii) unique to FLP or (iii) unique to HQT were screened from the STP, STITCH and TCMSP databases, and three corresponding core compound sets were identified in Herb-Compound-Target (H-C-T) networks. (3) Targets related to UC were identified from the DisGeNET and GeneCards databases and compared with the FLP-HQT common targets to identify potential targets of FLP-HQT compounds related to UC. (4) Three potential target sets were imported into the STRING database for protein‒protein interaction (PPI) analysis, and three core target sets were defined. (5) The binding capabilities and interacting modes between core compounds and key targets were verified by molecular docking via Discovery Studio 2019 and molecular dynamics (MD) simulations via Amber 2018. (6) The target sets were enriched for KEGG pathways using the DAVID database. RESULTS: (1) FLP and HQT included 95 and 113 active compounds, respectively, with 46 common compounds, 49 FLP-specific compounds and 67 HQT-specific compounds. (2) 174 targets of FLP-HQT common compounds, 168 targets of FLP-specific compounds, and 369 targets of HQT-specific compounds were predicted from the STP, STITCH and TCMSP databases; six core compounds specific to FLP and HQT were screened in the FLP-specific and HQT-specific H-C-T networks, respectively. (3) 103 targets overlapped from the 174 predicted targets and the 4749 UC-related targets; two core compounds for FLP-HQT were identified from the FLP-HQT H-C-T network. (4) 103 FLP-HQT-UC common targets, 168 of FLP-specific targets and 369 of HQT-specific targets had shared core targets (AKT1, MAPK3, TNF, JUN and CASP3) based on the PPI network analysis. (5) Molecular docking demonstrated that naringenin, formononetin, luteolin, glycitein, quercetin, kaempferol and baicalein of FLP and HQT play a critical role in treating UC; meanwhile, MD simulations revealed the stability of protein‒ligand interactions. (6) The enriched pathways indicated that most targets were related to anti-inflammatory, immunomodulatory and other pathways. Compared with the pathways identified using traditional methods, FLP-specific pathways included the PPAR signaling pathway and the bile secretion pathway, and HQT-specific pathways included the vascular smooth muscle contraction pathway and the natural killer cell-mediated cytotoxicity pathway etc. CONCLUSION: In this study, we clarified the common mechanisms of FLP and HQT in treating UC and their specific mechanisms in treating cold and heat syndrome in UC through compound, target and pathway distinction and a literature comparison based on network pharmacology; these results provide a new perspective on the detailed mechanism of "multidrugs and single-disease" thought in traditional Chinese medicine.

Molecular characterization of SPL gene family during flower morphogenesis and regulation in blueberry.

The SPL gene is a plant-specific transcription factor involved in the regulation of plant growth and development, which have been identified in woody plants. The process of floral bud differentiation affects the timing of flowering and fruit set and regulates plant growth, however, the mechanism of regulation of flower development by SPL genes is less studied. In this study, 56 VcSPL genes were identified in the tetraploid blueberry. The VcSPL gene family was classified into six subfamilies, and analysis of cis-elements showed that VcSPL genes were regulated by light, phytohormones (abscisic acid, MeJA), and low temperature. In the evolutionary analysis, segmental replication may play an important role in VcSPL gene amplification. Interestingly, we also studied diploid blueberry (Bilberry), in which 24 SPL genes were identified, and 36 homologous pairs were found, suggesting a high degree of convergence in the syntenic relationship between blueberry (Vaccinium corymbosum L) and bilberry (Vaccinium darrowii). Based on the expression profile, VcSPL genes were expressed at high levels in flowers, shoots, and roots, indicating a diversity of gene functions. Then we selected 20 differentially-expressed SPL genes to further investigate the role of VcSPL in floral induction and initiation. It showed that the genes VcSPL40, VcSPL35, VcSPL45, and VcSPL53 may play a crucial role in the blueberry floral transition phase (from vegetative growth to flower initiation). These results provided important information for understanding and exploring the role of VcSPLs in flower morphogenesis and plant growth.

Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment between T-Cells and lung tumor cells, suppress tumor cell migration and promoting CD8 expression in cytotoxic T-cells.

There has been a substantial and consistent rise in the number of clinical trials to develop advanced and potent bispecific antibodies (BsAb) over the past two decades with multiple targets to improve the efficacy or tissue specificity of monoclonal antibodies (mAb) treatment for diseases with multiple determining factors or widely-expressed targets. In this study, we designed and synthesized BsAb AGR2xPD1 targeting extracellular AGR2, a paracrine signal, and PD1, an immune checkpoint protein. Our design is intended to use AGR2 binding to guide PD1 targeting for AGR2+cancer. We used this construction to produce AGR2xPD1 BsAb by generating clonally selected stable 293F cell line with high expression. Applying this BsAb in a T cell-Tumor cell co-culture system showed that targeting both PD1 and AGR2 with this BsAb induces the attachment of TALL-104 (CD8+ T-lymphocytes) cells onto co-cultured H460 AGR2+ Lung tumor cells and significantly reduces migration of H460 cells. T-cell expression of CD8 and IFNγ is also synergistically enhanced by the AGR2xPD1 BsAb treatment in the AGR2+H460 co-culture system. These effects are significantly reduced with AGR2 expression negative WI38 cells. Our results demonstrate that the AGR2xPD1 BsAb could be a potential therapeutic agent to provide better solid tumor targeting and synergetic efficacy for treating AGR2+ cancer by blocking AGR2 paracrine signaling to reduce tumor survival, and redirecting cytotoxic T-cells into AGR2+ cancer cells.

A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy.

Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the ß-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.

Hepatoprotective effects of peach gum polysaccharides against alcoholic liver injury: moderation of oxidative stress and promotion of lipid metabolism.

Natural polysaccharides extracted from plants have received increasing attention due to their rich bioactivity. In our study, peach gum polysaccharides (PGPs) were extracted by water extraction-alcohol precipitation method. PGPs are typical pyranose polysaccharides with a mean molecular weight of 3.68 × 106 g/mol. The antioxidant activity and hepatoprotective capacity of PGPs were studied. In vitro, assays showed that PGPs scavenged DPPH, OH, and O2- in a dose-dependent manner. PGPs exhibited antioxidative properties against alcohol-induced HL7702 cells, as evidenced by the normalization of MDA, SOD, ROS, and GSH levels. To further elucidate the hepatoprotective mechanism of PGPs, we carried out in vivo experiments in male mice. PGPs exerted hepatoprotective effects in alcohol liver disease (ALD) mice by exerting antioxidant effects, decreasing the inflammatory response and modulating lipid metabolism. In addition, metabolomic analysis indicated that PGPs mainly regulate D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and arginine biosynthesis to promote hepatic metabolism and maintain body functions. Overall, this study revealed that the hepatoprotective mechanism of PGPs against ALD might be associated with the regulation of oxidative stress and lipid metabolism.

Trends in the Exposure, Distribution, and Health Risk Assessment of Perchlorate among Crayfish in the Middle and Lower Reaches of the Yangtze River.

Perchlorate is a well-known thyroid-disrupting chemical as well as an extremely stable inorganic pollutant widely distributed in the environment. Therefore, perchlorate posts potential risks to the environment as well as human health. Crayfish is a dominant aquatic food with increasing consumption levels in recent years. It is crucial to evaluate the accumulation of perchlorate with well-water-soluble properties in crayfish and to assess its health risks. In our present study, we obtained crayfish samples from cultivated ponds and markets based on the regions of the Middle and Lower Reaches of the Yangtze River. The perchlorate concentration was measured in all 206 samples using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Monte Carlo simulation was used to perform health risk assessments. The results indicated that perchlorate levels ranged from 7.74-43.71 µg/kg for cultivated crayfish and 4.90-16.73 µg/kg for crayfish sold in markets. The perchlorate accumulation mainly occurred in exoskeleton parts. All the HQ values were remarkable, at less than one-indicating that perchlorate exposure through the ingestion of crayfish does not pose an appreciable risk to human health.

Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants.

SARS-CoV-2 and its variants, such as the Omicron continue to threaten public health. The virus recognizes the host cell by attaching its Spike (S) receptor-binding domain (RBD) to the host receptor, ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here, we report the isolation and biological and structural characterization of a single-chain antibody (nanobody) from RBD-immunized alpaca. The nanobody, named DL28, binds to RBD tightly with a K D of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC50 of 0.41 µg mL-1. Neutralization assays with a panel of variants of concern (VOCs) reveal its wide-spectrum activity with IC50 values ranging from 0.35 to 1.66 µg mL-1 for the Alpha/Beta/Gamma/Delta and an IC50 of 0.66 µg mL-1 for the currently prevalent Omicron. Competition binding assays show that DL28 blocks ACE2-binding. However, structural characterizations and mutagenesis suggest that unlike most antibodies, the blockage by DL28 does not involve direct competition or steric hindrance. Rather, DL28 may use a "conformation competition" mechanism where it excludes ACE2 by keeping an RBD loop in a conformation incompatible with ACE2-binding.

An Open-Access Data Platform: Global Nutrition and Health Atlas (GNHA).

The rapid development of nutrition science is embracing digital transformation to generate large amounts of data. Precision nutrition and "Big Data" place increasing demand for data repositories and visualization, which enhances the digital transformation. We defined the need for an integrated nutrition data platform as a web-based platform that can collect, store, track, analyze, monitor, and visually display key metrics in nutrition and health while allowing users to interact with visuals and download data provided in the platform. Interactive dashboards create new opportunities for scholars and practitioners to generate and test hypotheses. We present the development and implementation of the Global Nutrition and Health Atlas (GNHA; https://sites.tufts.edu/gnha/), an open-access online platform covering nutrition and health data with 26 themes and 500+ indicators from 190+ countries up to 30 y. We view GNHA as an interactive tool aiming to share information and perspectives and foster collaborations and innovations.