Causal role of immune cells in thyroid cancer: a bidirectional Mendelian randomization study.

Background: The immune system plays an important role in the development and treatment of thyroid cancer(THCA).However, the correlation between immune cells and THCA has not been systematically studied. Methods: This study used a two-sample Mendelian randomization (MR) study to determine the causal relationship between immune cell characteristics and THCA. Based on a large sample of publicly available genetic data, we explored the causal relationship between 731 immune cell characteristics and THCA risk. The 731 immunophenotypes were divided into 7 groups, including B cell panel(n=190),cDC panel(n=64),Maturation stages of T cell panel(n=79),Monocyte panel(n=43),Myeloid cell panel(n=64),TBNK panel(n=124),and Treg panel(n=167). The sensitivity of the results was analyzed, and heterogeneity and horizontal pleiotropy were excluded. Results: After FDR correction, the effect of immunophenotype on THCA was not statistically significant. It is worth mentioning, however, that there are some unadjusted low P-values phenotypes. The odds ratio (OR) of CD62L on monocyte on THCA risk was estimated to be 0.953 (95% CI=0.930~0.976, P=1.005×10-4),and which was estimated to be 0.975(95% CI=0.961-0.989, P=7.984×10-4) for Resting Treg%CD4 on THCA risk. Furthermore, THCA was associated with a reduced risk of 5 immunophenotype:CD25 on CD39+ CD4 on Treg (OR=0.871, 95% CI=0.812~0.935, P=1.274×10-4), activated Treg AC (OR=0.884, 95% CI=0.820~0.953, P=0.001), activated & resting Treg % CD4 Treg (OR=0.872, 95%CI=0.811~0.937,P=2.109×10-4),CD28- CD25++ CD8br AC(OR=0.867,95% CI=0.809~0.930,P=6.09×10-5),CD28-CD127-CD25++CD8brAC(OR=0.875,95%CI=0.814~0.942,P=3.619×10-4).THCA was associated with an increased risk of Secreting Treg % CD4 Treg (OR=1.143, 95% CI=1.064~1.229, P=2.779×10-4) and CD19 on IgD+ CD24+ (OR=1.118, 95% CI=1.041~1.120, P=0.002). Conclusions: These findings suggest the causal associations between immune cells and THCA by genetic means. Our results may have the potential to provide guidance for future clinical research.

SnO2/Sn with core-shell structure Schottky heterojunctions loaded in graphene to promote electrochemical reaction kinetics and enable efficient lithium-ion storage.

The stannic oxide (SnO2) anode expands in volume during cycling causing a decrease in reversible capacity. In this work, we generated a spherical SnO2/Sn heterojunction with core-shell structure composites encapsulated by graphene (SnO2/Sn/G) in situ using a simple one-step hydrothermal and subsequent annealing process. SnO2/Sn heterojunction nanospheres dispersed in a porous graphene framework accelerate the diffusion kinetics of electrons and ions. In addition, the structure plays a key role in mitigating large volume changes and nanostructure agglomeration. As a result, SnO2/Sn/G exhibits excellent performance as an anode material for lithium-ion batteries (LIBs), maintaining a reversible specific capacity of 720.6 mA h g-1 even after 600 cycles at a current density of 0.5 A g-1.

Affinity-Resolved Size Exclusion Chromatography Coupled to Mass Spectrometry: A Novel Tool to Study the Attribute-and-Function Relationship in Therapeutic Monoclonal Antibodies.

Assessment of critical quality attributes (CQAs) is an important aspect during the development of therapeutic monoclonal antibodies (mAbs). Attributes that affect either the target binding or Fc receptor engagement may have direct impacts on the drug safety and efficacy and thus are considered as CQAs. Native size exclusion chromatography (SEC)-based competitive binding assay has recently been reported and demonstrated significant benefits compared to conventional approaches for CQA identification, owing to its faster turn-around and higher multiplexity. Expanding on the similar concept, we report the development of a novel affinity-resolved size exclusion chromatography-mass spectrometry (AR-SEC-MS) method for rapid CQA evaluation in therapeutic mAbs. This method features wide applicability, fast turn-around, high multiplexity, and easy implementation. Using the well-studied Fc gamma receptor III-A (FcγRIIIa) and Fc interaction as a model system, the effectiveness of this method in studying the attribute-and-function relationship was demonstrated. Further, two case studies were detailed to showcase the application of this method in assessing CQAs related to antibody target binding, which included unusual N-linked glycosylation in a bispecific antibody and Met oxidation in a monospecific antibody, both occurring within the complementarity-determining regions (CDRs).

Bioassay-Guided and DeepSAT-Driven Precise Mining of Monoterpenoid Coumarin Derivatives with Antifeedant Effects from the Leaves of Ailanthus altissima.

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella. Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico. The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease.

GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer.

Purpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.

Isolation of four new monoterpenes from Ailanthus altissima (mill.) Swingle and their enzyme inhibitory effects.

A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking.

Recent Progress of Anti-Freezing, Anti-Drying, and Anti-Swelling Conductive Hydrogels and Their Applications.

Hydrogels are soft-wet materials with a hydrophilic three-dimensional network structure offering controllable stretchability, conductivity, and biocompatibility. However, traditional conductive hydrogels only operate in mild environments and exhibit poor environmental tolerance due to their high water content and hydrophilic network, which result in undesirable swelling, susceptibility to freezing at sub-zero temperatures, and structural dehydration through evaporation. The application range of conductive hydrogels is significantly restricted by these limitations. Therefore, developing environmentally tolerant conductive hydrogels (ETCHs) is crucial to increasing the application scope of these materials. In this review, we summarize recent strategies for designing multifunctional conductive hydrogels that possess anti-freezing, anti-drying, and anti-swelling properties. Furthermore, we briefly introduce some of the applications of ETCHs, including wearable sensors, bioelectrodes, soft robots, and wound dressings. The current development status of different types of ETCHs and their limitations are analyzed to further discuss future research directions and development prospects.

Effects of multidisciplinary team continuous care model on psychological behavior and quality of life in children with ß-thalassemia major.

OBJECTIVE: To explore the effects of a multidisciplinary team (MDT) continuous care model on psychological behavior and quality of life in children with ß-thalassemia major (ß-TM). METHODS: A retrospective study was conducted on 90 children with ß-TM who were hospitalized in the Department of Pediatrics, Affiliated Hospital of Youjiang Medical University for Nationalities from October 2021 to May 2022. According to nursing methods, the children were divided into a routine group and an experimental group, with 45 cases in each group. The routine group was intervened with routine nursing approaches, and the experimental group was intervened with the MDT continuous nursing mode on the basis of the control group. The psychological behavior [Positive and Negative Affect Scale for Children (PANAS-C)], quality of life (QoL) [Pediatric Quality of Life Inventory TM (PedsQLTM)] and satisfaction were compared between the two groups before and 6 months after intervention. The hemoglobin level and ferritin level of children after 3 months and 6 months of intervention were measured. The occurrence of complications and nursing satisfaction were recorded. The prognostic factors were further analyzed. RESULTS: After the intervention, the positive emotion score, QoL score, hemoglobin level, satisfaction score in the experimental group were all higher than those in the conventional group, and the negative emotion score and ferritin level in the experimental group were all lower than those in the conventional group (all P < 0.05). The results of Cox analysis showed that the use of iron-removing drugs and arrhythmia/heart rate failure were risk factors affecting the prognosis of children with ß-TM, while the MDT continuous nursing mode was a protective factor (all P < 0.05). CONCLUSION: The MDT continuous care model can effectively promote mental health in children with ß-TM, improve their quality of life, medical satisfaction, ameliorate the degree of anemia in children, reduce the incidence of complications and improve the prognosis; thus, it is worthy of wide clinical application.

Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum.

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Structurally diverse 1,2-diarylpropanes from the fruit of Crataegus pinnatifida and the investigation on their mirror-image ECD spectra with the same absolute configurations.

1,2-diarylpropanes are a kind of abundant natural products formed by radical coupling. On account of molecular flexibility, it was challenged in the identifications of relative and absolute configurations of the 1,2-diarylpropanes. In this research, fourteen pairs of enantiomeric 1,2-diarylpropanes (1a/1b-14a/14b), comprising twelve previously undescribed pairs (1a/1b-4a/4b, 6a/6b-10a/10b, and 12a/12b-14a/14b), were isolated from the fruit of Crataegus pinnatifida. Their structures were determined through multiple NMR spectral analyses, empirical NMR rules, X-ray crystallography, and the comparison of experimental ECD spectra with calculated data. In addition, the analysis of ECD spectra revealed that substituent effects could generate an inverted chiroptical response, exhibiting in mirror-image ECD signals. This phenomenon was investigated by conformational analysis, molecular orbital analysis, the transition density matrix and hole/electron distributions. Moreover, a potential experimental rule was proposed for the rapid determination of the absolute configurations of the 1,2-diarylpropanes.

Target isolation of diverse sesquiterpenoid from the stems of Daphne genkwa based on molecular networking.

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023 µg/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

Molecular properties, structure and chiral resolution of secondary metabolites from the leaves of Viburnum chingii.

A chemical investigation of leaves of Viburnum chingii afforded eleven compounds, including one undescribed lignan (1), a pair of known phenylpropanoid enantiomers (2a/2b), and eight known lignans (3-10). Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. The absolute configurations of compounds 1 was determined by comparing the experimental ECD data with the calculated values. The compounds 2a/2b were separated successfully by a chiral chromatographic column. In addition, the acetylcholinesterase (AChE) inhibitory activities of described compounds were evaluated.

Isolation and characterization of seven neovibsane-type diterpenoids from Viburnum odoratissimum and their neuroblastoma cell protective effects.

Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh2(OCOCF3)4-induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 µM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 µM).

Eight structurally diverse components with anti-acetylcholinesterase activity from Daphne bholua.

Eight structurally diverse components, including six undescribed ones, (±)-daphuarin A (1a/1b), daphuarin B (2), daphuarin D-E (4-6), together with a pair of new natural products (±)-daphuarin C (3a/3b) were isolated from the herb of Daphne bholua Buch.-Ham. ex D. Don. Their planar structures were elucidated by extensive spectroscopic analyses. The configurations were established with the assistance of quantum chemical calculations, together with the Custom DP4+ method. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated.

Noble Metal Phosphides Supported on CoNi Metaphosphate for Efficient Overall Water Splitting.

Transition metal metaphosphates and noble metal phosphides prepared under similar conditions are potential hybrid catalysts for electrocatalytic water splitting, which is of great significance for H2 production. Herein, the structure and electrocatalytic activity of different noble metal species (i.e., Rh, Pd, Ir) on CoNiP4O12 nanoarrays have been systematically studied. Due to the different formation energies of noble metal phosphides, the phosphides of Rh (RhPx) and Pd (PdPx) as well as the noble metal Ir are obtained under the same phosphorylation conditions perspectively. RhPx/CoNiP4O12 and PdPx/CoNiP4O12 exhibit much better HER activity than Ir/CoNiP4O12 due to the advantages of phosphides. Density functional theory (DFT) calculations reveal that the extraordinary activity of RhPx/CoNiP4O12 originated from the strong affinity to H2O and optimal adsorption for H*. The best RhPx/CoNiP4O12 only requires a low overpotential of 30 and 234 mV to deliver 10 mA cm-2 for HER and OER, respectively, and therefore is effective for overall water splitting (requiring 1.57 V to achieve a current density of 10 mA cm-2). This work not only develops a novel RhPx/CoNiP4O12 electrocatalyst for overall water splitting but also provides deep insight into the formation mechanism of noble metal phosphides.

Diffusion-induced lithium isotopic heterogeneity in olivines from peridotites of an oceanized mantle lithosphere at the Yunzhug ophiolite (central Tibet).

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ7Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 µm. A negative correlation of δ7Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ7Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites.

Early-stage neutralizing antibody level associated with the re-positive risk of Omicron SARS-CoV-2 RNA in patients recovered from COVID-19.

Post-discharge re-positivity of Omicron SARS-CoV-2 is challenging for the sufficient control of this pandemic. However, there are few studies about the risk of re-positivity. We aimed to explore the association of neutralizing antibodies (nAbs, AU/mL) with the incidence of re-positivity among patients recovered from COVID-19. A retrospective cohort study selected 318 Omicron-infected patients was conducted in China between December 2021 and April 2022. The peak value of nAb levels (nAb-peak) within 14 days of disease onset was defined as the baseline and was mainly used for the subsequent analyses. In the unadjusted, minimally adjusted, fully adjusted, and additionally adjusted for IgG models, a per-standard deviation (SD) increase in the nAb-peak values was significantly associated with a 59 %, 59 %, 50 %, and 75 % decreased risk of Omicron SARS-CoV-2 re-positivity during post-discharge surveillance, respectively. Stratified analyses showed no significant changes in the relationship between nAbs and re-positivity. Our study suggested that the increase in baseline nAb levels independently associated with a low risk of re-positivity in patients recovered from COVID-19.

Synthesis of heterointerfaces in NiO/SnO2 coated nitrogen-doped graphene for efficient lithium storage.

Currently, it remains a challenge to make comprehensive improvements to overcome the disadvantages of volume expansion, Li2O irreversibility and low conductivity of SnO2. Heterostructure construction has been investigated as an effective strategy to promote electron transfer and surface reaction kinetics, leading to high electrochemical performance. Herein, NiO/SnO2 heterojunction modified nitrogen doped graphene (NiO/SnO2@NG) anode materials were prepared using hydrothermal and carbonization techniques. Based on the excellent structural advantages, sufficiently small NiO/SnO2 heterojunction nanoparticles increase the interfacial density to promote Li2O decomposition, and the built-in electric field accelerates the charge transport rate to improve the conductivity. The three-dimensional porous graphene framework effectively mitigates volume expansion during cycling and stabilizes the reactive interface of electrode materials. The results show that the NiO/SnO2@NG mixture has high reversible specific capacity (938.8 mA h g-1 after 450 cycles at 0.1 A g-1), superior multiplicity performance (374.5 mA h g-1 at 3.0 A g-1) and long cycle life (685.3 mA h g-1 after 1000 cycles at 0.5 A g-1). Thus, this design of introducing NiO to form heterostructures with SnO2 is directly related to enhancing the electrochemical performance of lithium-ion batteries (LIBs).

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.