Activation of nicotinic acetylcholine receptor α7 subunit limits Zika viral infection via promoting autophagy and ferroptosis.

Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999-2000.

BACKGROUND: Diet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults. METHODS: The data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999-2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status. RESULT: Based on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688-0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801-0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716-0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716-0.718) and cheese (OR = 0.863, 95% CI: 0.862-0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044-1.046) and added sugars (OR = 1.014, 95% CI: 1.013-1.015) were identified as risk factors for HP infection. CONCLUSION: Both the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2, accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the esophagus. Interestingly, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+ T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy. Collectively, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

Transforming Natural Eggshell and Diatomite into Bioactive Calcium Silicate Material for Bone Regeneration.

Calcium silicate (CS), a new and important bioceramic bone graft material, is prepared by using eggshells, which have a porous structure and are rich in calcium ions. Furthermore, the preparation of new CS materials using eggshells and diatomaceous earth minimizes their negative impact on the environment. In this study, we prepared CS materials using a high-temperature calcination method. The composition of the material was demonstrated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis. Scanning electron microscopy (SEM) analysis confirmed the porous structure of the CS material. We also introduced ZnO to prepare ZnO-CS with antibacterial properties and showed that ZnO-CS exhibits excellent antibacterial effects through in vitro antibacterial experiments. Subsequent in vitro mineralization experiments demonstrated that ZnO-CS promoted the formation of a hydroxyapatite layer. Furthermore, in vitro cytotoxicity experiments demonstrated that ZnO-CS had very good biosafety and promoted cell proliferation. These findings were confirmed through subsequent cell proliferation experiments. Our results indicate that the novel ZnO-CS is a promising candidate for bone tissue engineering.

Orthogonal Radical and Cationic Single-Unit Monomer Insertions for Engineering Polymer Architectures.

The single-unit monomer insertion (SUMI), derived from living/controlled polymerization, can be directly functionalized at the end or within the chain of polymers prepared by living/controlled polymerization, offering potential applications in the preparation of polymers with complex architectures. Many scenarios demand the simultaneous incorporation of monomers suitable for different polymerization methods into complex polymers. Therefore, it becomes imperative to utilize SUMI technologies with diverse mechanisms, especially those that are compatible with each other. Here, we reported the orthogonal SUMI technique, seamlessly combining radical and cationic SUMI approaches. Through the careful optimization of monomer and chain transfer agent pairs and adjustments to reaction conditions, we can efficiently execute both radical and cationic SUMI processes in one pot without mutual interference. The utilization of orthogonal SUMI pairs facilitates the integration of radical and cationic reversible addition-fragmentation chain transfer (RAFT) polymerization in various configurations. This flexibility enables the synthesis of diblock, triblock, and star polymers that incorporate both cationically and radically polymerizable monomers. Moreover, we have successfully implemented a mixing mechanism of free radicals and cations in RAFT step-growth polymerization, resulting in the creation of a side-chain sequence-controlled polymer brushes.

HLA-A+ tertiary lymphoid structures with reactivated tumor infiltrating lymphocytes are associated with a positive immunotherapy response in esophageal squamous cell carcinoma.

BACKGROUND: Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. However, the overall response rate to ICB therapy remains low in esophageal squamous cell carcinoma (ESCC). This study aimed to identify biomarkers of ICB therapy for ESCC and interrogate its potential clinical relevance. METHODS: We investigated gene expression in 42 treatment-naïve ESCC tumor tissues and identified differentially expressed genes, tumor-infiltrating lymphocytes and immune-related genes signatures associated with differential immunotherapy responses. We systematically assessed the tumor microenvironment using the NanoString GeoMx digital spatial profiler, single-cell RNA-seq and multiplex immunohistochemistry in ESCC. Finally, we evaluated the associations between HLA-A-positive tertiary lymphoid structures (TLSs) and patients' responses to ICB in 60 ESCC patients. RESULTS: Tumor infiltrating B lymphocytes and several immune-related gene signatures, such as the antigen presenting machinery (APM) signature, are significantly elevated in ICB treatment responders. Multiplex immunohistochemistry identified the presence of HLA-A+ TLSs and showed that TLS-resident cells increasingly express HLA-A as TLSs mature. Most TLS-resident HLA-A+ cells are tumor-infiltrating T (TIL-T) or tumor-infiltrating B (TIL-B) lymphocytes. Digital spatial profiling of spatially distinct TIL-T lymphocytes and single-cell RNA-seq data from 60 ESCC tumor tissues revealed that CXCL13-expressing exhausted TIL-Ts inside TLSs are reactivated with elevated expression of the APM signature as TLSs mature. Finally, we demonstrated that HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, are associated with a clinical benefit from ICB treatment for ESCC. CONCLUSIONS: HLA-A+ TLSs are present in ESCC tumor tissues. TLS-resident TIL-Ts with elevated expression of the APM signature may be reactivated. HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, may serve as biomarkers for ICB-treated ESCC patients.

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions.

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer.

Despite the promising outcomes of immune checkpoint inhibitors (ICIs), resistance to ICI presents a new challenge. Therefore, selecting patients for specific ICI applications is crucial for maximizing therapeutic efficacy. Herein, we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network and transcriptional signatures of T cells and myeloid cells define distinct ESCC subtypes characterized by T cell exhaustion, and interleukin (IL) and interferon (IFN) signaling. Furthermore, this approach classifies ESCC patients into ICI responders and non-responders, as validated by whole tumor transcriptomes and liquid biopsy-based single-cell transcriptomes of anti-PD-1 ICI responders and non-responders. Our study stratifies ESCC patients based on TME transcriptional network, providing novel insights into tumor niche remodeling and potentially predicting ICI responses in ESCC patients.

OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition.

Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 (OTUB2) is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance. Mechanistically, OTUB2 silencing destabilizes sorting nexin 29 pseudogene 2 (SNX29P2), which subsequently prevents hypoxia-inducible factor-1 alpha (HIF-1α) from von Hippel-Lindau tumor suppressor-mediated degradation. Elevated HIF-1α activates the transcription of carbonic anhydrase 9 (CA9) and drives ovarian cancer progression and chemoresistance by promoting glycolysis. Importantly, pharmacological inhibition of CA9 substantially suppressed tumor growth and synergized with carboplatin in the treatment of OTUB2-silenced ovarian cancer. Thus, our study highlights the pivotal role of OTUB2/SNX29P2 in suppressing ovarian cancer development and proposes that targeting CA9-mediated glycolysis is an encouraging strategy for the treatment of ovarian cancer.

Woody encroachment induced earlier and extended growing season in boreal wetland ecosystems.

Woody plant encroachment (WPE), a widespread ecological phenomenon globally, has significant impacts on ecosystem structure and functions. However, little is known about how WPE affects phenology in wetland ecosystems of middle and high latitudes. Here, we investigated the regional-scale effects of WPE on the start (SOS), peak (POS), end (EOS), and length (GSL) of the growing season in boreal wetland ecosystems, and their underlying mechanisms, using remote sensing dataset during 2001-2016. Our results showed that WPE advanced the annual SOS and POS, while delaying EOS and extending GSL in boreal wetlands with these impacts increasing over time. When boreal wetland ecosystems were fully encroached by woody plants, the SOS and POS were advanced by 12.17 and 5.65 days, respectively, the EOS was postponed by 2.74 days, and the GSL was extended by 15.21 days. We also found that the impacts of WPE on wetland SOS were predominantly attributed to the increased degree of WPE (α), while climatic factors played a more significant role in controlling the POS and EOS responses to WPE. Climate change not only directly influenced phenological responses of wetlands to WPE but also exerted indirect effects by regulating soil moisture and α. Winter precipitation and spring temperature primarily determined the effects of WPE on SOS, while its impacts on POS were mainly controlled by winter precipitation, summer temperature, and precipitation, and the effects on EOS were mainly determined by winter precipitation, summer temperature, and autumn temperature. Our findings offer new insights into the understanding of the interaction between WPE and wetland ecosystems, emphasizing the significance of considering WPE effects to ensure accurate assessments of phenology changes.

Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.

Bacillus-derived consortium enhances Ginkgo biloba's health and resistance to Alternaria tenuissima.

BACKGROUND: Bacillus, as a plant-growth-promoting rhizobacteria, can enhance the resistance of plants to phytopathogens. In our study, Bacillus strains showing excellent biocontrol were screened and used to control ginkgo leaf blight (Alternaria tenuissima). RESULTS: Four biocontrol Bacillus strains-Bsa537, Bam337, Bso544, and Bsu503-were selected from 286 isolates based on their capacity to inhibit pathogens and promote plant growth. The four Bacillus strains significantly improved the resistance of ginkgo to leaf blight. This was especially the case when the four strains were used as a mixture, which contributed to a decrease in lesion area of >40%. Hence, a mixture of Bacillus strains was used to control ginkgo leaf blight in the field. Treatment efficiency varied from 30% to 100% (average 81.5%) and was higher than that of the control (-2% to -18%, average - 8.5%); the antioxidant capacity of the treated ginkgo was also stronger. In addition, ginkgo biomass increased as a result of treatment with the Bacillus mixture, including leaf weight, area, thickness, number of lateral roots and root weight. Furthermore, the Bacillus mixture improved the ginkgo rhizosphere soil by boosting the number of beneficial microorganisms, lowering the number of pathogens and hastening soil catabolism. CONCLUSION: The Bacillus mixture improved the health status of ginkgo by protecting it from pathogen attack, promoting its growth and improving the microorganism community in the rhizosphere. This work closes a technological gap in the biological control of ginkgo leaf blight, investigates application methods for compound Bacillus biofertilizers and establishes a framework for the popularity and commercialization of these products. © 2024 Society of Chemical Industry.

Observing Proton-Electron Mixed Conductivity in Graphdiyne.

Mixed conducting materials with both ionic and electronic conductivities have gained prominence in emerging applications. However, exploring material with on-demand ionic and electronic conductivities remains challenging, primarily due to the lack of correlating macroscopic conductivity with atom-scale structure. Here, the correlation of proton-electron conductivity and atom-scale structure in graphdiyne is explored. Precisely adjusting the conjugated diynes and oxygenic functional groups in graphdiyne yields a tunable proton-electron conductivity on the order of 103. In addition, a wet-chemistry lithography technique for uniform preparation of graphdiyne on flexible substrates is provided. Utilizing the proton-electron conductivity and mechanical tolerance of graphdiyne, bimodal flexible devices serving as capacitive switches and resistive sensors are created. As a proof-of-concept, a breath-machine interface for sentence-based communication and self-nursing tasks with an accuracy of 98% is designed. This work represents an important step toward understanding the atom-scale structure-conductivity relationship and extending the applications of mixed conducting materials to assistive technology.

Correlation Between TRAb and Early Onset Hypothyroidism After 131I Treatment for Graves' Disease.

The aim of the study was to explore the clinical features related to early hypothyroidism and the relationship between the changes of thyrotropin receptor antibodies (TRAb) and early hypothyroidism in the course of 131I treatment for Graves' disease. This study was a retrospective observation, including 226 patients who received the first 131I treatment. The general information and laboratory tests were collected before and after 131I treatment, and the laboratory data affecting the difference in disease outcome were analyzed. According to the changes of antibodies in the third month, whether the changes of antibodies were involved in the occurrence of early-onset hypothyroidism was analyzed. Early onset hypothyroidism occurred in 165 of 226 patients, and the results showed that the incidence of early hypothyroidism was higher in patients with low baseline TRAb level (p=0.03) and increased TRAb after treatment (p=0.007). Both baseline TRAb levels (p<0.001) and the 24-hour iodine uptake rate (p=0.004) are significant factors influencing the changes in TRAb. The likelihood of a rise in TRAb was higher when the baseline TRAb was less than 18.55 U/l and the 24-hour iodine uptake level exceeded 63.61%. Low baseline and elevated post-treatment levels of TRAb were significantly associated with early-onset hypothyroidism after 131I treatment. Monitoring this index during RAI treatment is helpful in identifying early-onset hypothyroidism and mastering the clinical outcome and prognosis of Graves' disease.

Performance characterization and biocompatibility assessment of silicone polyurethanes for polymer heart valve applications.

Silicone polyurethanes have gained widespread application in the biomedical field due to their excellent biocompatibility. This study comprehensively investigates four silicone polyurethane materials suitable for polymer heart valves, each exhibiting distinct chemical compositions and structural characteristics, leading to significant differences, particularly in mechanical performance and biocompatibility. Surface analysis reveals an elevated surface silicon element content in all materials compared to the bulk, indicating a migration of silicon elements towards the surface, providing a structural basis for enhancing biological stability and biocompatibility. However, higher silicon content leads to a decrease in mechanical performance, potentially resulting in mechanical failure and rupture in artificial heart valves. Concerning biocompatibility, an increase in silicone content diminishes the material's adsorption capability for cells and proteins, consequently improving its biocompatibility and biological stability. In summary, while high silicone content leads to a reduction in mechanical performance, the formation of a "silicon protective layer" on the material surface mitigates cell and protein adsorption, thereby enhancing biocompatibility and biological stability. Through comprehensive testing of the four silicone polyurethane materials, this study aims to provide insightful perspectives and methods for selecting materials suitable for polymer heart valves. Additionally, the thorough performance exploration of these materials serves as a crucial reference for the performance assessment and biocompatibility research of polymeric artificial heart valve materials.

A Quadrivalent mRNA Immunization Elicits Potent Immune Responses against Multiple Orthopoxviral Antigens and Neutralization of Monkeypox Virus in Rodent Models.

The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo raised public health concerns about the threat of human-to-human transmission of zoonotic diseases. Currently available vaccines may not be sufficient to contain outbreaks of a more transmissible and pathogenic orthopoxvirus. Development of a safe, effective, and scalable vaccine against orthopoxviruses to stockpile for future emergencies is imminent. In this study, we have developed an mRNA vaccine candidate, ALAB-LNP, expressing four vaccinia viral antigens A27, L1, A33, and B5 in tandem in one molecule, and evaluated the vaccine immunogenicity in rodent models. Immunization of animals with the candidate mRNA vaccine induced a potent cellular immune response and long-lasting antigen-specific binding antibody and neutralizing antibody responses against vaccinia virus. Strikingly, the sera from the vaccine-immunized mice cross-reacted with all four homologous antigens of multiple orthopoxviruses and neutralized monkeypox virus in vitro, holding promise for this mRNA vaccine candidate to be used for protection of humans from the infection of monkeypox and other orthopoxvirus.

piRNAs as emerging biomarkers and physiological regulatory molecules in cardiovascular disease.

Cardiovascular diseases (CVD) represent one of the most considerable global health threats, owing to their high incidence and mortality rates. Despite the ongoing advancements in detection, prevention, treatment, and prognosis of CVD, which have resulted in a decline in both incidence and mortality rates, CVD remains a major public health concern. Therefore, novel diagnostic biomarkers and therapeutic interventions are imperative to minimise the risk of CVD. Non-coding RNAs (ncRNAs) have recently gained increasing attention, with PIWI-interacting RNAs (piRNAs) emerging as a class of small ncRNAs traditionally recognised for their role in silencing transposons within cells. Although the functional roles of PIWI proteins and piRNAs in human cells remain unclear, growing evidence suggests that these molecules are gradually becoming valuable biomarkers for the diagnosis and treatment of CVD. This review provides a comprehensive summary of the latest studies on piRNAs in CVD. This review discusses the roles of piRNAs in various cardiovascular subtypes, including myocardial hypertrophy, heart failure, myocardial infarction, and cardiac regeneration. The perceived insights may contribute novel perspectives for the diagnosis and treatment of CVD.

Intestinal toxicity of Pb: Structural and functional damages, effects on distal organs and preventive strategies.

Lead (Pb) is one of the most common heavy metal pollutants that possesses multi-organ toxicity. For decades, great efforts have been devoted to investigate the damage of Pb to kidney, liver, bone, blood cells and the central nervous system (CNS). For the common, dietary exposure is the main avenue of Pb, but our knowledge of Pb toxicity in gastrointestinal tract (GIT) remains quite insufficient. Importantly, emerging evidence has documented that gastrointestinal disorders affect other distal organs like brain and liver though gut-brain axis or gut-liver axis, respectively. This review focuses on the recent understanding of intestinal toxicity of Pb exposure, including structural and functional damages. We also review the influence and mechanism of intestinal toxicity on other distal organs, mainly concentrated on brain and liver. At last, we summarize the bioactive substances that reported to alleviate Pb toxicity, providing potential dietary intervention strategies to prevent or attenuate Pb toxicity.

Highly-sensitive optical thermometer developed based on an intervalence charge transfer mashup.

Optical thermometers based on lanthanide thermal-coupled levels have attracted great attention owing to its fundamental importance in the fields of public health, biology, and integrated circuit. However, the inherent structural properties (shielded effect on 4f configurations, intense non-radiation relaxation) strictly suppress the sensing performance, limiting the relative temperature sensitivity (SR). To circumvent these limitations, we propose an intervalence charge transfer mashup strategy by inducing d0 electron configured transition metals. Specifically, transition metals Ta5+ is incorporated in Tm3+/Eu3+:LiNbO3, which improves the SR from 5.30 to 11.16% K-1. The validity of this component-modulation behavior is observed on other oxide crystals (NaY(Mo1-zWzO4)2) as well. Furthermore, the observed regulation is well explained by DFT calculation that indicates the d-orbit component at valence band minimum remains the core factor governing the electron transfer process. We successfully relate the SR to the band structure of luminescence carrier, offering a novel perspective for the collocation design of lanthanide configurations.