Long-Term Follow-Up of Combination Therapy with Sintilimab and Anlotinib in Gallbladder Follicular Dendritic Cell Sarcoma: A Rare Case Report.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm for which a standardized treatment approach has yet to be established. The prevailing therapeutic strategy typically involves resection followed by adjuvant chemotherapy or radiation. This case report details the long-term follow-up of a 59-year-old Chinese male diagnosed with gallbladder FDCS and liver metastases. The patient received a combination therapy of sintilimab and anlotinib, resulting in a substantial partial response (PR) lasting for a noteworthy duration of 30 months. Notably, this is the first documented instance of gallbladder FDCS with liver metastases being treated with PD-1 antibody and antiangiogenic agents as first-line therapy. These findings suggest that this treatment regimen may offer a potential therapeutic option for patients with gallbladder FDCS and liver metastases, with a duration of PR lasting up to 30 months.

Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression.

BACKGROUND: Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. METHODS: A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. RESULTS: We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. CONCLUSIONS: NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.

Reduction of haemoglobin is related to metal mixtures exposure in Chinese preschoolers: Joint effect models.

Heavy metal exposure is a known risk factor for hematologic disorders in children, yet the impact of co-exposure to multiple metals remains underexplored. This cross-sectional study investigates the relationship between urinary levels of 23 metals and haemoglobin (Hb) in 1460 Chinese preschoolers. The concentrations of the 23 urinary metals were quantified using an inductively coupled plasma mass spectrometer, while Hb levels were assessed through finger prick blood samples. To evaluate the co-exposure effects, we employed three approaches: Generalized linear regression model, joint effect models including Quantile g-Computation and Bayesian Kernel Machine Regression (BKMR). From the generalized linear regression and Quantile g-computation, urinary uranium, thallium, aluminium, iron and tungsten were correlated negatively with Hb, while urinary barium was correlated positively (all P < 0.05). Moreover, significant negative associations between metal mixtures exposure with Hb were identified in both Quantile g-computation [ß (95% CI): -0.083 (-0.132, -0.033), P = 0.0012] and BKMR [90th percentile vs. 50th percentile ß (95% CI): -0.238 (-0.368, -0.107), P < 0.001] with aluminium emerging as the primary contributor to this joint effect (weight in Quantile g-computation = 0.399, PIPs in BKMR = 0.896). These findings provide a potential explanation for environmental exposure to metals and Hb-related disease in preschoolers.

Wheat Protein Hydrolysates Improving the Stability of Purple Sweet Potato Anthocyanins under Neutral pH after Commercial Sterilization at 121 °C.

Anthocyanins are prone to degradation and color fading after sterilization. This work examined the potential of wheat protein hydrolysates (WPHs, 40 g/L) in improving the stability of purple sweet potato anthocyanins (PSPAs) under a pH of 6.8 after sterilization at 121 °C followed by storage. Results showed that WPHs increased the thermal degradation half-life of PSPAs 1.65 times after sterilization. Compared to PSPAs alone, after being stored at 37 °C and 45 °C for 7 days, the retention concentration of PSPAs with WPHs was 5.4 and 32.2 times higher, and the color change of PSPAs with WPHs decreased from 6.19 and 10.46 to 0.29 and 0.77, respectively. AFM data, fluorescence and UV spectrograms indicated the formation of complexes between PSPAs and WPHs by hydrophobic attraction confirmed by zeta-potential data. PSPAs with WPHs had stable particle size and zeta potential, which may also significantly increase the concentrations after digestion and antioxidant power of PSPAs. This work indicated that the assembled PSPAs composite structure by WPHs significantly reduced the degradation of PSPAs at a pH of 6.8 after sterilization at 121 °C followed by long-term storage.

Three-dimensional finite element analysis on stress distribution after different palatoplasty and levator veli palatini muscle reconstruction.

OBJECTIVES: To establish a three-dimensional finite element model of the upper palate, pharyngeal cavity, and levator veli palatini muscle in patients with unilateral complete cleft palate, simulate two surgical procedures that the two-flap method and Furlow reverse double Z method, observe the stress distribution of the upper palate soft tissue and changes in pharyngeal cavity area after different surgical methods, and verify the accuracy of the model by reconstructing and measuring the levator veli palatini muscle. MATERIALS AND METHODS: Mimics, Geomagic, Ansys, and Hypermesh were applied to establish three-dimensional finite element models of the pharyngeal cavity, upper palate, and levator veli palatini muscle in patients with unilateral complete cleft palate. The parameters including length, angle, and cross-sectional area of the levator veli palatini muscle etc. were measured in Mimics, and two surgical procedures that two-flap method and Furlow reverse double Z method were simulated in Ansys, and the area of pharyngeal cavity was measured by hypermesh. RESULTS: A three-dimensional finite element model of the upper palate, pharyngeal cavity, and bilateral levator veli palatini muscle was established in patients with unilateral complete cleft palate ; The concept of horizontal projection characteristics of the palatal dome was applied to the finite element simulation of cleft palate surgery, vividly simulating the displacement and elastic stretching of the two flap method and Furlow reverse double Z method during the surgical process; The areas with the highest stress in the two-flap method and Furlow reverse double Z method both occur in the hard soft palate junction area; In resting state, as measured, the two flap method can narrow the pharyngeal cavity area by 50.9%, while the Furlow reverse double Z method can narrow the pharyngeal cavity area by 65.4%; The measurement results of the levator veli palatini muscle showed no significant difference compared to previous studies, confirming the accuracy of the model. CONCLUSIONS: The finite element method was used to establish a model to simulate the surgical procedure, which is effective and reliable. The area with the highest postoperative stress for both methods is the hard soft palate junction area, and the stress of the Furlow reverse double Z method is lower than that of the two-flap method. The anatomical conditions of pharyngeal cavity of Furlow reverse double Z method are better than that of two-flap method in the resting state. CLINICAL RELEVANCE: This article uses three-dimensional finite element method to simulate the commonly used two-flap method and Furlow reverse double Z method in clinical cleft palate surgery, and analyzes the stress distribution characteristics and changes in pharyngeal cavity area of the two surgical methods, in order to provide a theoretical basis for the surgeon to choose the surgical method and reduce the occurrence of complications.

Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens.

This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, and metabolomic studies, we dissected the mechanisms by which mitochondrial genetic variations dictate cancer progression. Emphasis has been placed on the roles of these genes in altering cellular metabolic processes, signal transduction pathways, and immune system interactions. We further explored how these findings could refine therapeutic interventions, with a particular focus on precision medicine applications. This analysis not only fills pivotal knowledge gaps about mitochondrial anomalies in pancreatic cancer but also paves the way for future investigations into personalized therapy options. This finding underscores the crucial nexus between mitochondrial genetics and oncological immunology, opening new avenues for targeted cancer treatment strategies.

TyG-GGT is a Reliable Non-Invasive Predictor of Advanced Liver Fibrosis in Overweight or Obese Individuals.

BACKGROUND: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. METHOD: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. RESULTS: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. CONCLUSIONS: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group.

The toxic effects of petroleum pollutants to microalgae in marine environment.

Marine oil pollution is one of the major global environmental pollution problems. Marine microalgae are the foundation of the marine food chain, providing the main primary productivity of the ocean. They not only maintain the energy flow and material cycle of the entire marine ecosystem, but also play an important role in regulating global climate change. Exploring the impact of petroleum pollutants on marine microalgae is extremely important for studying marine environmental pollution. This review first introduced the sources, compositions, and forms of petroleum pollutants and their migration and transformation processes in the ocean. Then, the toxic effects of petroleum pollutants on marine microalgae were summarized. The growth of marine microalgae showed low-concentration promotion and high-concentration inhibition. The population growth and interspecific relationships of marine microalga was changed and the photosynthesis of marine microalgae was influenced. Finally, potential research directions and suggestions for marine microalgae in the future were proposed.

A chromosome-level genome of electric catfish (Malapterurus electricus) provided new insights into order Siluriformes evolution.

The electric catfish (Malapterurus electricus), belonging to the family Malapteruridae, order Siluriformes (Actinopterygii: Ostariophysi), is one of the six branches that has independently evolved electrical organs. We assembled a 796.75 Mb M. electricus genome and anchored 88.72% sequences into 28 chromosomes. Gene family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate receptors. Convergent evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like (arhgef4), which is associated with G-protein coupled receptor (GPCR) signaling pathway, underwent adaptive parallel evolution. Gene identification suggests visual degradation in catfishes, and an important role for taste in environmental adaptation. Our findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00197-8.

Highly sensitive detection of tryptophan based on Schiff base reaction and surface-enhanced Raman spectroscopy.

In this study, a simple, rapid and sensitive method combining surface-enhanced Raman spectroscopy and Schiff base reaction was developed for the detection of tryptophan. This method does not require product separation to obtain a significant Raman signal of the derivatized product, and the derivatization reaction can be controlled by experimental parameters such as reaction temperature, time, concentration of derivatization reagent and concentration of sodium nitrite. The characteristic peak of the derivative of tryptophan (1620 cm-1) was selected for quantitative analysis, and the intensity of the characteristic Raman spectrum peak showed a linear relationship with the concentration of tryptophan (10-8-10-4 mol/L) in the range of with a correlation coefficient R2 of 0.9922. This assay combines surface-enhanced Raman spectroscopy and Schiff base reaction, which is characterized by high sensitivity and easy operation, and has good application prospects in the detection of tryptophan in food.

The Effect of Central Sensitization on Postoperative Neurocognitive Dysfunction in Hospitalized Elderly Patients: A Prospective Cohort Clinical Trial.

OBJECTIVE: To investigate whether central sensitization (CS) in elderly patients was a predictive risk factor for postoperative neurocognitive dysfunction (PNCD). METHODS: One hundred and thirty-three aged patients undergoing total knee arthroplasty (TKA) who received femoral nerve block and general anesthesia were recruited in this research and prospectively assigned into two groups according to the Central Sensitization Inventory (CSI) score: group C (n = 106, CSI score less than 40) and group CS (n = 27, CSI score higher than 40). Scores of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM), Numerical Rating Scale (NRS) and Quality of recovery-40 (QoR-40) questionnaires were assessed. Basic information and clinical records of all participants were also collected. RESULTS: PNCD occurred in 24 (22.6%) of patients in group C and 16 (59.3%) in group CS (p < .05). Multivariate logistic regression analysis revealed that patients with CSI score ≥40 before surgery exhibited higher risk of PNCD after adjustment for other risk factors (p < .05). Compared to group C, the pre- and post-operative NRS scores, pain duration, the WOMAC score, and propofol consumptions for anesthesia induction were significantly increased in group CS (p < .05). CONCLUSION: Hospitalized elderly patients with clinical symptoms of CS scores may have increased risk of PNCD following TKA.

An Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) Method for Qualifying DAPB in Rat Plasma and Application to Pharmacokinetic Studies.

DAPB, a new molecule including danshensu, borneol, and a mother nucleus of ACEI (Angiotensin-converting enzyme inhibitors), is being developed as an antihypertensive candidate compound. A rapid, accurate, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the determination of DAPB in rat plasma. Chromatographic separation was performed on an Agilent SB-C18 column after protein precipitation by acetonitrile with a mobile phase consisting of acetonitrile and deionized water with 0.02% formic acid and 5 mM NH4F (v/v) at a flow rate of 0.2 mL/min. Quantification was performed using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The method was linear over the range of 2-1000 ng/mL. The intra- and inter-day precision was within 12%, with accuracies less than 7%. Stability was within the acceptable limits under various storage and processing conditions. No apparent matrix effect was detected. The validated method was applied to the pre-clinical pharmacokinetic study of DAPB after oral administration of 30 mg/kg and intravenous administration of 6 mg/kg in rats.

The landscape of the methodology in drug repurposing using human genomic data: a systematic review.

The process of drug development is expensive and time-consuming. In contrast, drug repurposing can be introduced to clinical practice more quickly and at a reduced cost. Over the last decade, there has been a significant expansion of large biobanks that link genomic data to electronic health record data, public availability of various databases containing biological and clinical information and rapid development of novel methodologies and algorithms in integrating different sources of data. This review aims to provide a thorough summary of different strategies that utilize genomic data to seek drug-repositioning opportunities. We searched MEDLINE and EMBASE databases to identify eligible studies up until 1 May 2023, with a total of 102 studies finally included after two-step parallel screening. We summarized commonly used strategies for drug repurposing, including Mendelian randomization, multi-omic-based and network-based studies and illustrated each strategy with examples, as well as the data sources implemented. By leveraging existing knowledge and infrastructure to expedite the drug discovery process and reduce costs, drug repurposing potentially identifies new therapeutic uses for approved drugs in a more efficient and targeted manner. However, technical challenges when integrating different types of data and biased or incomplete understanding of drug interactions are important hindrances that cannot be disregarded in the pursuit of identifying novel therapeutic applications. This review offers an overview of drug repurposing methodologies, providing valuable insights and guiding future directions for advancing drug repurposing studies.

Dynamic reading in a digital age: new insights on cognition.

People increasingly read text displayed on digital devices, including computers, handheld e-readers, and smartphones. Given this, there is rapidly growing interest in understanding how the cognitive processes that support the reading of static text (e.g., books, magazines, or newspapers) might be adapted to reading digital texts. Evidence from recent experiments suggests a complex interplay of visual and cognitive influences on how people engage with digital reading. Although readers can strategically adjust their reading behaviors in response to their immediate reading context, the efficacy of these strategies depends on cognitive, metacognitive, and motivational factors. A better understanding of the factors that influence reading offers the promise of leveraging digital technologies to enhance the reading experience.

SERS detection of foodborne pathogens in beverage with Au nanostars.

The aim of this study is to develop a simple but rapid method for the determination of foodborne pathogens in complex matrices (beverages) by surface enhanced Raman spectroscopy (SERS) combined with Au nanostar solid-phase substrates. The star-shaped singlet Au nanostructure was formed on the surface of a stainless steel sheet by chemical replacement reaction. Rhodamine 6G verified the sensitivity and reproducibility of this substrate, and the relative standard deviations of the SERS intensity at 1312 cm-1, 1364 cm-1, and 1510 cm-1 displacements were 3.40%, 5.64%, and 3.48%, respectively. By detecting four pathogens in beverage samples on Au nanostar substrates, the utility of the SERS assay was demonstrated, while the combination of principal component analysis (PCA) and hierarchical cluster analysis (HCA) further enabled the isolation and identification of pathogens. The results of spiked beverages were validated in conventional culture identification and Vitek 2 Compact biochemical identification system experiments. Thus, this research demonstrated that Au nanostar substrates can be effectively utilized for the recognition of pathogenic bacteria and have immense promise to advance the progress of quick detection of foodborne pathogens and food safety.

Constructing a 3D interconnected network of Ag nanostructures for high-performance SERS detection of food coloring agents.

The design and preparation of various effective three-dimensional (3D) silver nanostructures is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). This paper demonstrates a simple and novel method for the preparation of a substrate, whose surface was covered by a 3D interconnected network of Ag nanostructures, and the resulting network structure surface is free of organic contaminants. The EDS measurements confirm the metallic nature of the formed 3D Ag nanonetwork substrate. Additionally, the influence of experimental parameters on the morphology of the 3D Ag nanonetwork was also investigated, such as reaction time, hydrofluoric acid concentration, silver nitrate concentration and sodium citrate concentration. The 3D Ag nanonetwork has good uniformity. Importantly, the 3D Ag nanonetwork substrate was used to accurately and reliably detect amaranth (AR) and sunset yellow (SY) in beverages, with the lowest detection limit of 3 and 0.1 µg L-1, respectively. Therefore, this substrate is expected to be a promising candidate for SERS detection and offers attractive potential for a wider range of applications.

The EMT-Related Genes GALNT3 and OAS1 are Associated with Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma.

BACKGROUND: Lung cancer is the main cause of cancer-related death, with epithelial-mesenchymal transition (EMT) playing an important role in the development of this disease. The EMT-related genes Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) and 2'-5'-Oligoadenylate Synthetase 1 (OAS1) are involved in numerous tumor processes. Although these genes have been extensively studied in cancer, they have yet to be analyzed by multi-omics in lung adenocarcinoma (LUAD). METHODS: EMT-related genes were identified by R and Venn diagram. Cox regression and Kaplan-Meier analysis were performed to evaluate patient survival, and the Gene Expression Profiling Interactive Analysis (GEPIA) database was used for correlation analysis. GeneCards and R packages were used to explore gene characterization and functional annotation. The Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), University of Alabama at Birmingham Cancer (UALCAN), and The Cancer Genome Atlas (TCGA) databases were used to investigate gene expression, which was then confirmed by RT-PCR. Clinicopathological analysis was carried out using the UALCAN database. Functional mechanisms and multi-omics analysis were performed using DNA Methylation Interactive Visualization Database (DNMIVD), Targetscan, TIMER, Tumor-immune System Interactions Database (TISIDB) and cBioportal. Diagnostic values were calculated using ROC curve analysis. RESULTS: A total of 320 EMT-related genes were identified in LUAD. Their characteristics were confirmed in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database by the intersection of 855 and 3600 different genes from the Gene Expression Omnibus (GEO) and EMTome databases, respectively. Expression of the EMT-related genes GALNT3 and OAS1 was associated with the prognosis of LUAD patients. A positive correlation was observed between the expression of GALNT3 and OAS1, and their expression was higher in LUAD tissue than in normal lung tissue. This was confirmed using RT-PCR. Multi-omics analysis revealed that GALNT3 and OAS1 expression was associated with gene mutation and methylation, cellular immune infiltration, and several immune subtypes. A miRNA-GALNT3/OAS1 regulatory network was also found. Receiver operating characteristic (ROC) curve analysis found that GALNT3 and OAS1 expression combined had superior diagnostic value to that of each marker alone. CONCLUSIONS: GALNT3 and OAS1 expression are associated with immune cell infiltration and poor prognosis in LUAD. Their combined expression has high diagnostic value; hence, GALNT3 and OAS1 may be valuable biomarkers for the early detection of LUAD.