The stability of CsPb(BrxCl1-x)3 all-inorganic mixed halide perovskites.

The use of mixed halide perovskites in the preparation of blue light-emitting diodes (LEDs) is considered to be the most effective and direct approach. However, the introduction of chlorine (Cl) element might raise stability issues in the system and lead to low efficiency, thereby impeding the development of deep blue light-emitting diodes with high efficiency and stability. Determining the alloy concentration and the atomic distribution of bromine-chlorine (Br-Cl) mixed systems is essential for further application of deep blue light-emitting diodes. In this work, we have systematically investigated the stability of bromine-chlorine (Br-Cl) mixed alloy systems in various substitution configurations using high-throughput theoretical calculations. Based on this, we have examined the relationship between configuration stability and three aspects: the type of octahedra, the orientation of the octahedra and the Pb-X-Pb distortion angle in the configuration.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes.

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δß|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Candidate membrane protein gene families related to chemoreception in a wood-boring beetle, Pharsalia antennata Gahan (Coleoptera: Cerambycidae).

The longhorned beetles are key players for the maintenance of biodiversity in the terrestrial ecosystem. As xylophagous cerambycid insects in Coleoptera, the beetles have evolved specialized olfactory and gustatory systems to recognize chemical cues in the surrounding habitats. Despite over 36,000 described species in the Cerambycidae family including a wood-boring pest Pharsalia antennata, only a limited number of them (<1 %) have been characterized regarding their chemical ecology at the molecular level. Here, we surveyed four membrane protein gene families in P. antennata related to chemoreception through transcriptomics, phylogenetics and expression profiling analyses. In total, 144 genes encoding 72 odorant receptors (ORs), 33 gustatory receptors (GRs), 23 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs) and 12 ionotropic glutamate receptors (iGluRs) were harvested from the transcriptome of multiple tissues including antennae and legs of both sexes. The lineage-specific expansion of PantORs possibly implied a diverse range of host plants in this beetle, supporting this correlation between the host range and olfactory receptor repertoire sizes across cerambycid species. Further phylogenetic analysis revealed that Group 2 was contributed mainly to the large OR gene repertoire in P. antennata, representing 18 genes in Group 2A and eight in Group 2B. On the other hand, some key chemosensory genes were identified by applying a phylogenetics approach, such as PantOR21 close to the 2-phenylethanol receptor in Megacyllene caryae, three carbon dioxide GRs and seven Antennal IRs (A-IRs) clades. We also determined sex- and tissue-specific expression profiles of 69 chemosensory genes, revealing the high expression of most PantORs in antennae. Noticeably, 10 sex-biased genes (six PantORs, three PantIRs and PantSNMP1a) were presented in antennae, five sex-biased PantGRs in legs and 39 sex-biased genes (15 PantORs, 13 PantGRs, eight PantIRs and three PantSNMPs) in abdomens. These findings have greatly enhanced our knowledge about the chemical ecology of P. antennata and identify candidate molecular targets for mediating smell and taste of this beetle.

Pre-therapy PET-based voxel-wise dosimetry prediction by characterizing intra-organ heterogeneity in PSMA-directed radiopharmaceutical theranostics.

BACKGROUND AND OBJECTIVE: Treatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET. METHODS: 23 patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA I&T RPT were retrospectively included. 48 treatment cycles with pre-treatment PET imaging and at least 3 post-therapeutic SPECT/CT imaging were selected. The distribution of PET tracer and RPT dose was compared for kidney, liver and spleen, characterizing intra-organ heterogeneity differences. Pharmacokinetic simulations were performed to enhance the understanding of the correlation. Two strategies were explored for pre-therapy voxel-wise dosimetry prediction: (1) organ-dose guided direct projection; (2) deep learning (DL)-based distribution prediction. Physical metrics, dose volume histogram (DVH) analysis, and identity plots were applied to investigate the predicted absorbed dose map. RESULTS: Inconsistent intra-organ patterns emerged between PET imaging and dose map, with moderate correlations existing in the kidney (r = 0.77), liver (r = 0.5), and spleen (r = 0.58) (P < 0.025). Simulation results indicated the intra-organ pharmacokinetic heterogeneity might explain this inconsistency. The DL-based method achieved a lower average voxel-wise normalized root mean squared error of 0.79 ± 0.27%, regarding to ground-truth dose map, outperforming the organ-dose guided projection (1.11 ± 0.57%) (P < 0.05). DVH analysis demonstrated good prediction accuracy (R2 = 0.92 for kidney). The DL model improved the mean slope of fitting lines in identity plots (199% for liver), when compared to the theoretical optimal results of the organ-dose approach. CONCLUSION: Our results demonstrated the intra-organ heterogeneity of pharmacokinetics may complicate pre-therapy dosimetry prediction. DL has the potential to bridge this gap for pre-therapy prediction of voxel-wise heterogeneous dose map.

Theoretical Insights into the Effect of Different Numbers of Thiophene Groups on Hydrogen Bond Interaction and Excited-State Intramolecular Proton-Transfer Process for Flavonoid Derivatives.

In this study, we systematically explored the impact of varying the number of thiophene groups on the hydrogen bond interaction and excited-state intramolecular proton-transfer (ESIPT) processes in flavonoid derivatives (STF, DTF, and TTF) using the density functional theory and time-dependent density functional theory methods. Initially, a thorough analysis of the optimized geometric structures revealed that the intramolecular hydrogen bond in the S1 state is enhanced and gradually weakened as the number of thiophene groups increases. To gain a deeper understanding of the hydrogen bond interaction, topological analysis, interaction region indicator scatter plots, and isosurface plots were employed. These images provide further insights that align with the structural analysis. Additionally, we observed a red-shift in the electronic spectra (absorption and fluorescence spectra), which is primarily attributed to the narrowing of the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, as elucidated by the frontier molecular orbitals. Furthermore, a combined analysis between the hole-electron distribution and the transition density matrix heat map shows that electron excitation involves the unidirectional charge-transfer mechanism. In the end, by conducting relaxed potential energy curve scans, we found that an increase in the number of thiophene groups elevates the energy barrier for ESIPT, making it more challenging for the reaction. In summary, our study underscores the vital effect of thiophene-substituted numbers in modulating the ESIPT process, which is able to provide valuable insights for the design and synthesis of desired organic fluorescent probes in the future.

SLC34A2 Targets in Calcium/Phosphorus Homeostasis of Mammary Gland and Involvement in Development of Clinical Mastitis in Dairy Cows.

The type II Na/Pi co-transporter (NaPi2b), encoded by the solute carrier (SLC) transporter 34A2 (SLC34A2), is responsible for calcium (Ca) and phosphorus (P) homeostasis. Unbalanced Ca/P metabolism induces mastitis in dairy cows. However, the specific role of SLC34A2 in regulating this imbalance in Holstein cows with clinical mastitis (CM) remains unclear. The aim of this study was to investigate the role of SLC34A2 and identify differentially expressed proteins (DEPs) that interact with SLC34A2 and are associated with Ca/P metabolism in dairy cows with CM. Immunohistochemical and immunofluorescence staining results showed that SLC34A2 was located primarily in the mammary epithelial cells of the mammary alveoli in both the control (healthy cows, Con/C) and CM groups. Compared to the Con/C group, the relative expression of the SLC34A2 gene and protein were significantly downregulated in the CM group. We identified 12 important DEPs included in 11 GO terms and two pathways interacting with SLC34A2 using data-independent acquisition proteomics. The PPI (protein-and-protein interaction) network results suggested that these DEPs were associated with ion metabolism and homeostasis, especially SLC34A2. These results demonstrate that SLC34A2 downregulation is negatively correlated with the occurrence and development of CM in Holstein cows, providing a basis for exploring the function and regulatory mechanism of SLC34A2 in Ca/P metabolism and homeostasis in Holstein cows with CM.

Establishment of a Simple, Sensitive, and Specific Salmonella Detection Method Based on Recombinase-Aided Amplification Combined with dsDNA-Specific Nucleases.

Salmonella is a common foodborne pathogen that can cause food poisoning, posing a serious threat to human health. Therefore, quickly, sensitively, and accurately detecting Salmonella is crucial to ensuring food safety. For the Salmonella hilA gene, we designed Recombinase-aided amplification (RAA) primers and dsDNA-specific nuclease (DNase) probes. The ideal primer and probe combination was found when conditions were optimized. Under UV light, a visual Salmonella detection technique (RAA-dsDNase) was developed. Additionally, the RAA-dsDNase was modified to further reduce pollution hazards and simplify operations. One-pot RAA-dsDNase-UV or one-pot RAA-dsDNase-LFD was developed as a Salmonella detection method, using UV or a lateral flow dipstick (LFD) for result observation. Among them, one-pot RAA-dsDNase and one-pot RAA-dsDNase-LFD had detection times of 50 min and 60 min, respectively, for detecting Salmonella genomic DNA. One-pot RAA-dsDNase-UV had a detection limit of 101 copies/µL and 101 CFU/mL, while one-pot RAA-dsDNase-LFD had a sensitivity of 102 copies/µL and 102 CFU/mL. One-pot RAA-dsDNase-UV and one-pot RAA-dsDNase-LFD assays may identify 17 specific Salmonella serovars witho ut causing a cross-reaction with the remaining 8 bacteria, which include E. coli. Furthermore, Salmonella in tissue and milk samples has been reliably detected using both approaches. Overall, the detection method developed in this study can quickly, sensitively, and accurately detect Salmonella, and it is expected to become an important detection tool for the prevention and control of Salmonella in the future.

Identification of NINJ1 as a novel prognostic predictor for retroperitoneal liposarcoma.

BACKGROUND: Retroperitoneal liposarcoma (RPLS) is known for its propensity for local recurrence and short survival time. We aimed to identify a credible and specific prognostic biomarker for RPLS. METHODS: Cases from The Cancer Genome Atlas (TCGA) sarcoma dataset were included as the training group. Co-expression modules were constructed using weighted gene co-expression network analysis (WGCNA) to explore associations between modules and survival. Survival analysis of hub genes was performed using the Kaplan-Meier method. In addition, independent external validation was performed on a cohort of 135 Chinese RPLS patients from the REtroperitoneal SArcoma Registry (RESAR) study (NCT03838718). RESULTS: A total of 19 co-expression modules were constructed based on the expression levels of 26,497 RNAs in the TCGA cohort. Among these modules, the green module exhibited a positive correlation with overall survival (OS, p = 0.10) and disease-free survival (DFS, p = 0.06). Gene set enrichment analysis showed that the green module was associated with endocytosis and soft-tissue sarcomas. Survival analysis demonstrated that NINJ1, a hub gene within the green module, was positively associated with OS (p = 0.019) in the TCGA cohort. Moreover, in the validation cohort, patients with higher NINJ1 expression levels displayed a higher probability of survival for both OS (p = 0.023) and DFS (p = 0.012). Multivariable Cox analysis further confirmed the independent prognostic significance of NINJ1. CONCLUSIONS: We here provide a foundation for the establishment of a consensus prognostic biomarker for RPLS, which should not only facilitate medical treatment but also guide the development of novel targeted drugs.

Analysis and validation of biomarkers of immune cell-related genes in postmenopausal osteoporosis: An observational study.

Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.

Factors Affecting Neutrophil Functions During Sepsis: Human Microbiome and Epigenetics.

Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense anti-bacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation and play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There's a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps (NETs) is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis where dysbiosis may occur. We highlight the importance of deciphering neutrophil's functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for sepsis diagnostic method when used in combination with the cell-free DNA (cfDNA). Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cfDNA, could serve as biomarkers for the early detection of sepsis.

The first selective VAP-1 inhibitor in China, TT-01025-CL: safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multiple-ascending doses.

Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers. Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10-300 mg [single dose]; 20-100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers. Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100-300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25-0.5 h post-dose and was maintained 48-168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20-100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups. Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development.

Vanadium pentoxide interfacial layer enables high performance all-solid-state thin film batteries.

Lithium cobalt oxide (LiCoO2) is considered as one of the promising building blocks that can be used to fabricate all-solid-state thin film batteries (TFBs) because of its easy accessibility, high working voltage, and high energy density. However, the slow interfacial dynamics between LiCoO2 and LiPON in these TFBs results in undesirable side reactions and severe degradation of cycling and rate performance. Herein, amorphous vanadium pentoxide (V2O5) film was employed as the interfacial layer of a cathode-electrolyte solid-solid interface to fabricate all-solid-state TFBs using a magnetron sputtering method. The V2O5 thin film layer assisted in the construction of an ion transport network at the cathode/electrolyte interface, thus reducing the electrochemical redox polarization potential. The V2O5 interfacial layer also effectively suppressed the side reactions between LiCoO2 and LiPON. In addition, the interfacial resistance of TFBs was significantly decreased by optimizing the thickness of the interfacial modification layer. Compared to TFBs without the V2O5 layer, TFBs based on LiCoO2/V2O5/LiPON/Li with a 5 nm thin V2O5 interface modification layer exhibited a much smaller charge transfer impedance (Rct) value, significantly improved discharge specific capacity, and superior cycling and rate performance. The discharge capacity remained at 75.6% of its initial value after 1000 cycles at a current density of 100 µA cm-2. This was mainly attributed to the enhanced lithium ion transport kinetics and the suppression of severe side reactions at the cathode-electrolyte interface in TFBs based on LiCoO2/V2O5/LiPON/Li with a 5 nm V2O5 thin layer.

Influence of atomic electronegativity on ESIPT behaviour for the BTDI and its derivatives: Theoretical exploration.

In this work, we theoretically explored the influence of atomic electronegativity on excited-state intramolecular proton transfer (ESIPT) behavior among novel fluorescent probes BTDI and its derivatives (BODI and BSeDI). A thorough examination of the optimized structural parameters and infrared vibrational spectra reveals an enhancement in intramolecular hydrogen bonding within BTDI and its derivatives upon light excitation. This finding is further reinforced by topological analysis and interaction region indicator scatter plots, which underscores the sensitivity of atomic electronegativity to variations in hydrogen bonding strength. With regards to absorption and fluorescence spectra, the decrease in atomic electronegativity leads to a pronounced redshift, primarily attributed to the narrowing of the energy gap. Additionally, an analysis of potential energy curves and the exploration of intrinsic reaction coordinate paths based on transition state structures afford a deeper understanding of the mechanism underlying ESIPT and being modulated through the manipulation of atomic electronegativity. We anticipate that this work on atomic electronegativity regulating ESIPT behavior will serve as a catalyst for novel fluorescent probes in the future, offering fresh perspectives and insights.

Three species of rape responded to cadmium and melatonin alleviating Cd-toxicity in species-specific strategy.

Cadmium (Cd) pollution has been a significant concern in heavy metal pollution, prompting plants to adopt various strategies to mitigate its damage. While the response of plants to Cd stress and the impact of exogenous melatonin has received considerable attention, there has been limited focus on the responses of closely related species to these factors. Consequently, our investigation aimed to explore the response of three different species of rape to Cd stress and examine the influence of exogenous melatonin in this scenario. The research findings revealed distinctive responses among the investigated rape species. B. campestris showed the resistance to Cd and exhibited lower Cd absorption and sustained its physiological activity under Cd stress. In contrast, B. juncea accumulated much Cd and increased the amount of anthocyanin to mitigate the Cd-damage. Furthermore, B. napus showed the tolerance to Cd and tended to accumulate Cd in vacuoles under Cd stress, thereby decreasing the Cd damage and leading to higher activity of antioxidant enzymes and photosynthesis. Moreover, the application of exogenous melatonin significantly elevated the melatonin level in plants and mitigated Cd toxicity by promoting the activity of antioxidant enzymes, reducing Cd absorption, enhancing the chelating capacity with Cd, decreasing Cd accumulation in organelles, and reducing its fluidity. Specifically, exogenous melatonin increased the FHAc content in B. campestris, elevated the phytochelatins (PCs) level in B. napus, and stimulated photosynthesis in B. juncea. In summary, the findings underscore the species-specific responses of the three species of rape to both Cd stress and exogenous melatonin, highlighting the potential for tailored mitigation strategies based on the unique characteristics of each species.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

piSTING: A Pocket-Independent Agonist Based on Multivalency-Driven STING Oligomerization.

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket-independent STING-activating agonists (piSTINGs), which act through multivalency-driven oligomerization to activate STING. Additionally, a piSTING-adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING-based vaccine combination with aPD-1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists.

Risk assessment models for PICC-related venous thrombosis in adult patients with cancer: A network meta-analysis.

OBJECTIVES: This review aims to compare the performance of available risk assessment models (RAMs) for predicting peripherally inserted central catheter-related venous thrombosis (PICC-RVT) in adult patients with cancer. METHODS: A systematic search was conducted across ten databases from inception to October 20, 2023. Studies were eligible if they compared the accuracy of a RAM to that of another RAM for predicting the risk of PICC-RVT in adult patients with cancer. Two reviewers independently performed the study selection, data extraction and risk of bias assessments. A Bayesian network meta-analysis (NMA) was used to evaluate the performance of the RAMs. RESULTS: A total of 1931 studies were screened, and 7 studies with 10 RAMs were included in the review. The most widely used RAMs were the Caprini (4 studies), Padua prediction score (3 studies), Autar (3 studies), Michigan risk score (2 studies) and Seeley score (2 studies). The sensitivity, specificity and accuracy varied markedly between the models. Notably, the Caprini score achieved higher sensitivity than 4 RAMs (Wells, Revised Geneva, modified MRS, MRS). The Michigan risk score had greater specificity than did the other 6 RAMs (Caprini, Autar, Padua, Seeley, the novel RAM, Wells). The predictive accuracy of the MRS is significantly greater than that of the Caprini and Autar RAM. CONCLUSION: The MRS could be the most accurate RAM for identifying patients at high risk of PICC-RVT. However, as limited studies are available, more rigorous studies should be conducted to examine the accuracy of the Michigan risk score for PICC-RVT in different contexts.

Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.

Treatment of mice with maternal intermittent fasting to improve the fertilization rate and reproduction.

Maternal intermittent fasting (MIF) can have significant effects on several tissue and organ systems of the body, but there is a lack of research on the effects on the reproductive system. So, the aim of our study was to analyze the effects of MIF on fertility. B6C3F1Crl (C57BL/6N × C3H/HeN) male and female mice were selected for the first part of the experiments and were analyzed for body weight and fat weight after administration of the MIF intervention, followed by analysis of sperm counts and activation and embryo numbers. Subsequently, two strains of mice, C57BL/6NCrl and BALB/cJRj, were selected and administered MIF to observe the presence or absence of vaginal plugs for the purposes of mating success, sperm and oocyte quality, pregnancy outcome, fertility status and in vitro fertilization (IVF). Our results showed a significant reduction in body weight and fat content in mice receiving MIF intervention in B6C3F1Crl mice. Comparing the reproduction of the two strains of mice. However, the number of litters was increased in all MIF interventions in C57BL/6NCrl, but not statistically significant. In BALB/cJRj, there was a significant increase in the number of pregnant females as well as litter size in the MIF treatment group, as well as vaginal plugs, and IVF. There was also an increase in sperm activation and embryo number and the MIF intervention significantly increased sperm count and activation. Our results suggest that MIF interventions may be beneficial for reproduction in mice.

Mini Endoscopic Septoplasty for High Localized Nasal Septum Deviation: Surgical Technique, Outcomes, and Comparison With Regular Septoplasty.

OBJECTIVES: This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty. METHODS: Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months. RESULTS: Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma. CONCLUSION: Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.