Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.

AIMS: The purpose of this study was to investigate the role of DGUOK in the pro-gression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment. METHODS: We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was inves-tigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy. RESULTS: Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This ef-fect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in au-tophagy pathways. CONCLUSION: These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment.

Emerging nanocellulose from agricultural waste: Recent advances in preparation and applications in biobased food packaging.

With the increasing emphasis on sustainability and eco-friendliness, a novel biodegradable packaging materials has received unprecedented attention. Nanocellulose, owing to its high crystallinity, degradability, minimal toxicity, and outstanding biocompatibility, has gained considerable interest in the field of sustainable packaging. This review provided a comprehensive perspective about the recent advances and future development of cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs). We first introduced the utilization of agricultural waste for nanocellulose production, such as straw, bagasse, fruit byproducts, and shells. Next, we discussed the preparation process of nanocellulose from various agricultural wastes and expounded the advantages and shortcomings of different methods. Subsequently, this review offered an in-depth investigation on the application of nanocellulose in food packaging, especially the function and packaged form of nanocellulose on food preservation. Finally, the safety evaluation of nanocellulose in food packaging is conducted to enlighten and promote the perfection of relevant regulatory documents. In short, this review provided valuable insights for potential research on the biobased materials utilized in future food packaging.

The 3-year follow-up of a fully biodegradable implantable device closure for perimembranous ventricular septal defects in children using echocardiography.

Objects: The aim of this study was to investigate the morphologic changes of a novel fully biodegradable implantable device after closing a perimembranous ventricular septal defect (Pm-VSD) and to evaluate the effect of the occluder on the myocardial function in patients during a 3-year follow-up period. Methods: One-year, 2-year, and 3-year follow-ups were carried out after implantation with a total of 30 Pm-VSD patients who had successful closure by the fully biodegradable occluder. In total, 30 healthy children were enrolled as controls. At discharge and at every follow-up visit, the lengths of the left and right discs of the novel device were measured in the apical three- and four-chamber as well as short-axis views. At the end of the follow-up, using three-dimensional speckle-tracking conditions, the values of myocardial deformation, including global longitudinal strain, global circumferential strain, and global area strain, were acquired. Results: The fully bioabsorbable double-disc occluder gradually decreased over time and was eventually invisible under echocardiographic scanning during the follow-up (p < 0.05). At the end of the third year, there were no significant differences in the myocardial deformation parameters between the cases implanted with the novel devices and the controls; no significant differences were found between the basal segments of the ventricle septa and that of the left ventricle (LV) free wall among the patients who completed the Pm-VSD closure using the fully biodegradable occluder (p > 0.05). Conclusion: The novel fully biodegradable occluder is a safe, effective, and perfect alternative for the treatment of VSD. Echocardiography plays a crucial role in the follow-up of this new type of occluder implantation.

The oral microbiome and oral and upper gastrointestinal diseases.

Background: Microbiomes are essential components of the human body, and their populations are substantial. Under normal circumstances, microbiomes coexist harmoniously with the human body, but disturbances in this equilibrium can lead to various diseases. The oral microbiome is involved in the occurrence and development of many oral and gastrointestinal diseases. This review focuses on the relationship between oral microbiomes and oral and upper gastrointestinal diseases, and therapeutic strategies aiming to provide valuable insights for clinical prevention and treatment. Methods: To identify relevant studies, we conducted searches in PubMed, Google Scholar, and Web of Science using keywords such as "oral microbiome," "oral flora, " "gastrointestinal disease, " without any date restrictions. Subsequently, the retrieved publications were subject to a narrative review. Results: In this review, we found that oral microbiomes are closely related to oral and gastrointestinal diseases such as periodontitis, dental caries, reflux esophagitis, gastritis, and upper gastrointestinal tumors (mainly the malignant ones). Oral samples like saliva and buccal mucosa are not only easy to collect, but also display superior sample stability compared to gastrointestinal tissues. Consequently, analysis of the oral microbiome could potentially serve as an efficient preliminary screening method for high-risk groups before undergoing endoscopic examination. Besides, treatments based on the oral microbiomes could aid early diagnosis and treatment of these diseases. Conclusions: Oral microbiomes are essential to oral and gastrointestinal diseases. Therapies centered on the oral microbiomes could facilitate the early detection and management of these conditions.

1. Various microbiomes exist in the oral cavity. 2. Under normal circumstances, oral microbes and human health coexist in harmony, once this balance is broken, it may cause a variety of diseases. 3. Oral microbiota are associated with upper digestive diseases, which are expected to be an effective triage for high-risk population before endoscopic screening.

Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin.

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1-15). Acetate of these derivatives were prepared (compounds 1a-15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

A review on triterpenoid and triterpenoid saponins from Xanthoceras sorbifolium Bung.

Xanthoceras sorbifolium Bunge, also known as Tu-Mu-Gua and Wen-Dan-Ge-Zi, has several applications. Clinical data and experimental studies have shown anti-tumor, anti-inflammatory, anti-bacterial, and anti-oxidant properties of Xanthoceras sorbifolium Bunge that inhibits prostate hyperplasia, lowers blood pressure and lipid level, and treats enuresis and urinary incontinence. It also has neuroprotective effects and can treat Alzheimer's disease and Parkinson's syndrome. The research on the chemical composition and pharmacological effects of Xanthoceras sorbifolium Bunge has been increasing. Triterpenoid and triterpenoid saponins are the main constituents in Xanthoceras sorbifolium Bunge and exhibit biological activities. In this review, we summarized the research progress on triterpenoids and their glycosides in Xanthoceras sorbifolia, including the chemical constituents, pharmacological activities, and biogenic pathways of triterpenoid mother nucleus. The results would provide a reference for further research and development of triterpenoids and their glycosides in Xanthoceras sorbifolia.

The Effect of Carboxymethyl Cellulose Sodium on the Proofing Tolerance and Quality of Frozen Dough Steamed Bread.

This study investigated the effects of dough proofing degree (1.1, 1.3, 1.5, and 1.7 mL/g) and carboxymethyl cellulose sodium (CMC-Na) on the quality of frozen dough steamed bread (FDSB). As the dough proofing degree was increased from 1.1 to 1.7 mL/g, the specific volume of FDSB initially increased and then decreased, with the maximum at 1.3 mL/g, and then dramatically decreased at 1.5 and 1.7 mL/g, accompanied by a harder texture and secession of crust and crumb, which were the detrimental effects brought by over-proofing. The optimal amount of CMC-Na effectively alleviated the deterioration associated with over-proofing, and the proofing tolerance of FDSB was increased from 1.3 mL/g to 1.7 mL/g. Fermentation analysis showed that CMC-Na significantly improved the extensibility and gas-holding capacity of the dough by increasing the maximum height of the dough (Hm) and the emergence time (T1) of Hm. Frequency sweep tests indicated that CMC-Na improved the plasticity of proofed dough by increasing loss factor tan δ. Significant reductions were found in peak viscosity and complex modulus G* in pasting properties tests and temperature sweep measurements, respectively, suggesting that CMC-Na influenced starch gelatinization and dough stiffening during steaming, which promoted the extension of the network structure, thus facilitating gas expansion and diffusion. These property changes theoretically explained the improvement in the proofing tolerance of FDSB by CMC-Na.

Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature.

The effect of renal functional status on drug metabolism is a crucial consideration for clinicians when determining the appropriate dosage of medications to administer. In critically ill patients, there is often a significant increase in renal function, which leads to enhanced drug metabolism and potentially inadequate drug exposure. This phenomenon, known as augmented renal clearance (ARC), is commonly observed in pediatric critical care settings. The findings of the current study underscore the significant impact of ARC on the pharmacokinetics and pharmacodynamics of antimicrobial drugs in critically ill pediatric patients. Moreover, the study reveals a negative correlation between increased creatinine clearance and blood concentrations of antimicrobial drugs. The article provides a comprehensive review of ARC screening in pediatric patients, including its definition, risk factors, and clinical outcomes. Furthermore, it summarizes the dosages and dosing regimens of commonly used antibacterial and antiviral drugs for pediatric patients with ARC, and recommendations are made for dose and infusion considerations and the role of therapeutic drug monitoring. CONCLUSION:  ARC impacts antimicrobial drugs in pediatric patients. WHAT IS KNOWN: • ARC is inextricably linked to the failure of antimicrobial therapy, recurrence of infection, and subtherapeutic concentrations of drugs. WHAT IS NEW: • This study provides an updated overview of the influence of ARC on medication use and clinical outcomes in pediatric patients. • In this context, there are several recommendations for using antibiotics in pediatric patients with ARC: 1) increase the dose administered; 2) prolonged or continuous infusion administration; 3) use of TDM; and 4) use alternative drugs that do not undergo renal elimination.

Phytochemical Constituents from the Seeds of Capsella bursa-pastoris and Their Antioxidant Activities.

Phytochemical investigation of 70% EtOH extract of the seeds of Capsella bursa-pastoris led to the isolation of a new cyclobutane organic acid (1), and fourteen known compounds, including two organosulfur compounds (2, 3), two quinonoids (4, 5), five flavonoids (6-10), three sterols (11-13) and two other types (14, 15). The structures of the compounds were elucidated by extensive spectroscopic analyses as well as comparison of their spectroscopic data with those reported in the literature. The antioxidant capacities of all compounds and extractive fractions were evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging test and ferric reducing antioxidant power (FRAP) assay. Then the antioxidative substances were evaluated for their neuroprotective effects against H2O2-induced HT22 cell injury. The results indicated the strong scavenging ability to free radical of the extractive fractions and compounds 1-3, 8-10 and 13, and the ferric reducing antioxidant power of the extractive fractions and compounds 1-3, 8 and 10, which were close to or higher than that of the positive control trolox. The EtOAc fraction, n-BuOH fraction, and compounds 1, 3 and 8 can protect HT-22 cells from oxidative damage.

Orychophragine D:A new 2-piperazinone fused 5-azacytosine type alkaloid with radioprotective activity from the seeds of Orychophragmus violaceus.

A new alkaloid, Orychophragine D (1), together with three known alkaloids, were isolated from the seeds of Orychophragmus violaceus. Orychophragine D represented the first example of 2-piperazinone fused 5-azacytosine skeleton. Their structures and absolute configurations were determined by spectroscopic analyses and X-ray crystallography. Compared to Ex-RAD, compound 1 exhibited a significant radioprotective activity on cell survival of irradiated HUVEC. In vivo experiments showed that 1 not only remarkably enhanced the survival of irradiated mice in 30 days, but also significantly promoted the recovery of the blood system of irradiated mice. These results suggested that 1 was valuable for further research as promising radioprotectors.

Skeleton Synthesis of a Plant-Derived Radioprotective Alkaloid Born to Produce a Novel Fused Heterocycle.

Alkaloids are a material treasure bestowed on humans by nature owing to their numerous biological activities. Orychophragine D, an alkaloid isolated from the seeds of Orychophragmus violaceus was identified as bearing a novel skeleton and proved to have an excellent radioprotective effect. Different from the common alkaloid structure, the main block of orychophragine D is constructed of an oxotriazine and an oxopiperazine, which are connected in parallel by a C-N bond. In this paper, a preparation method for the novel heterocycle skeleton of orychophragine D is proposed for the first time. N-Boc-L-serine was utilized as the original material to complete the preparation with 11 steps in a 13% overall yield. A hydroxyl group was established on the side chain of the skeleton as the reaction site for researchers to conduct further structural modification or derivatization.

Global research trends of endoscope in early gastric cancer: A bibliometric and visualized analysis study over past 20 years.

Objectives: Early gastric cancer (EGC) is defined as aggressive gastric cancer involving the gastric mucosa and submucosa. Early detection and treatment of gastric cancer are beneficial to patients. In recent years, many studies have focused on endoscopic diagnosis and therapy for EGC. Exploring new methods to analyze data to enhance knowledge is a worthwhile endeavor, especially when numerous studies exist. This study aims to investigate research trends in endoscopy for EGC over the past 20 years using bibliometric analysis. Methods: Original articles and reviews examining the use of endoscopy for EGC published from 2000 to 2022 were retrieved from the Web of Science Core Collection, and bibliometric data were extracted. Microsoft Office Excel 2016 was used to show the annual number of published papers for the top 10 countries and specific topics. VOSviewer software was used to generate network maps of the cooccurrences of keywords, authors, and topics to perform visualization network analysis. Results: In total, 1,009 published papers met the inclusion criteria. Japan was the most productive country and had the highest number of publications (452, 44.8%), followed by South Korea (183, 18.1%), and China (150, 14.9%). The National Cancer Center of Japan was the institution with the highest number of publications (48, 4.8%). Ono was the most active author and had the highest number of cited publications. Through the network maps, exploring endoscopic diagnosis and therapy were major topics. Artificial intelligence (AI), convolutional neural networks (CNNs), and deep learning are hotspots in endoscopic diagnosis. Helicobacter pylori eradication, second-look endoscopy, and follow-up management were examined. Conclusions: This bibliometric analysis investigated research trends regarding the use of endoscopy for treating EGC over the past 20 years. AI and deep learning, second-look endoscopy, and management are hotspots in endoscopic diagnosis and endoscopic therapy in the future.

Synthesis, Structure-Activity Relationship, and Mechanism of a Series of Diarylhydrazide Compounds as Potential Antifungal Agents.

A series of simple diarylhydrazide derivatives (45 examples) were well-designed, prepared, and screened for their antifungal activities both in vitro and in vivo. Bioassay results suggested that all designed compounds had significant activity against Alternaria brassicae (EC50 = 0.30-8.35 µg/mL). Among of them, 2c, as the highest activity compound, could effectively inhibit the growth of plant pathogens Pyricularia oryza, Fusarium solani, Alternaria solani, Alternaria brassicae, and Alternaria alternate and was more potent than carbendazim and thiabendazole. 2c showed almost 100% protection at 200 µg/mL in vivo activity against A. solani in tomato. Moreover, 2c did not affect the germination of cowpea seed and the growth of normal human hepatocytes. The preliminary mechanistic exploration documented that 2c could result in the abnormal morphology and irregular structure of the cell membrane, destroy the function of mitochondria, increase the reactive oxygen species, and inhibit the proliferation of hypha cell. The above results manifested that target compound 2c could be a potential fungicidal candidate against phytopathogenic diseases for its excellent fungicidal activities.

Discovery of pentacyclic triterpenoid glycosides with anti-proliferative activities from Ardisialindleyana.

One new pentacyclic triterpenoid glycoside, ardisiapunine E (1), along with two known compounds were isolated from the root of Ardisia lindleyana D.Dietr. Their structures were elucidated by 1H and 13C NMR, DEPT, HMBC, HSQC, 1H-1H COSY and NOESY spectroscopic analyses, ESI-MS, and literature. Compounds 1-3 exhibited obvious anti-proliferative activities against the HeLa cell line in a dose- and time-dependent manner by inducing G2/M phase arrest and apoptosis in vitro, both consisting of pentacyclic triterpenes and sugar. Hence, this study identified a new and two known pentacyclic triterpenoid glycosides promoting apoptosis as a potential anti-proliferative agent.

Four organosulfur compounds from the seeds of Capsella bursa-pastoris and their anti-inflammatory activities.

Phytochemical investigation of the seeds of Capsella bursa-pastoris led to the isolation of four organosulfur compounds. There were two new compounds, 10-methylsulfinyl-decanamide (1) and 11-methylsulfinyl-undecanamide (2), along with two known compounds (3 - 4), which all have a sulfoxide group and an amide or a nitrile group. Their chemical structures were elucidated by analysing UV, IR, ESI-MS and NMR spectroscopy. In addition, compounds 1 - 4 were evaluated for their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 1 - 4 exhibited potential anti-inflammatory activities on NO release characterised by decreasing the mRNA expression levels of inducible NO synthase (iNOS), cytokines cyclooxygenase-2 (COX-2) and interleukin 6 (IL-6).

Low Muscle Mass Is Associated with Readmission for Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease tend to have malnutrition, frailty, and low muscle mass, which impact on poor clinical outcomes. Abdominal computed tomography is frequently used to assess body composition. This study aimed to evaluate the association of low muscle mass and readmission within 1 year in patients with inflammatory bowel disease during hospitalization and follow-up. METHODS: A total of 211 patients with inflammatory bowel disease who had undergone computed tomography scans were included retrospectively. They were divided into subgroups based on disease activity. The male patients with skeletal muscle index ≤45.4 cm2/m2 and the female patients with skeletal muscle index ≤ 34.3 cm2/m2 were considered to have low muscle mass. Sociodemographic, clinical, and prognostic data were recorded. The analyses were done using the Statistical Package for the Social Sciences 25.0 software. RESULTS: The prevalence rate of low muscle mass was 64.7%. Low body mass index and hemoglobin, high erythrocyte sedimentation rate, smoking, and gastrointestinal surgery history were risk factors for low muscle mass (P < .05). Patients using steroids and biologics and using them more than 7 months were prone to develop low muscle mass and readmission (P < .05), while patients using immunomodulators were not. Inflammatory bowel disease patients with visceral fat area/subcutaneous fat area ≥0.71 were likely to readmit within 1 year than those with visceral fat area/subcutaneous fat area <0.71 (P < .05). Overweight or obese inflammatory bowel disease patients with low muscle mass had a shorter time to readmission than those without low muscle mass (P < .05). CONCLUSIONS: Overweight/obese inflammatory bowel disease patients with low muscle mass and patients using steroids and biologics have shorter time to readmission within 1 year regardless of disease activity.

The complete chloroplast genome sequence of the water fern Ceratopteris thalictroides (Pteridaceae).

This work determined and analyzed the complete chloroplast genome sequence of Ceratopteris thalictroides (Linnaeus) Brongniart 1822 (Pteridaceae). The results indicate that the total chloroplast genome size of C. thalictroides is 149,399 bp in length, and the genome contains a large single-copy (LSC) region of 83,580 bp, a small single-copy (SSC) region of 21,241 bp, and a pair of inverted repeat (IR) regions of 22,289 bp. The GC content of C. thalictroides is 36.7%. The genome encodes a total of 131 unique genes, including 82 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The phylogenetic analysis results strongly suggest that C. thalictroides is closely related to C. cornuta.

Absolute Configuration and Biological Evaluation of Novel Triterpenes as Possible Anti-Inflammatory or Anti-Tumor Agents.

Two new compounds, ardisiapunine B (1) and ardisiapunine C (2), were isolated from Ardisia lindleyana D. Dietr. Their structures were examined using HR-ESI-MS, IR, (1D, 2D) NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD calculation. It was found that the two new compounds belong to unusual oleanane-type triterpenes, with compound 1 bearing an acetal unit and a C-13-C-18 double bond, and compound 2 bearing a C-28 aldehyde group and a C-18-C-19 double bond. The anti-inflammatory properties of compounds 1 and 2 were tested on NO production and cellular morphology using RAW264.7 cells, and their anti-tumor properties were tested on cytotoxic activities, cellular morphology, cell apoptosis, and cell cycle. The results showed that compound 1 exhibited a potent cytotoxicity against HepG2 cell lines with an IC50 of 12.40 µM. Furthermore, it is possible that compound 1 inhibits cell proliferation by blocking the cell G2/M phase and promoting cell apoptosis. Compound 2 exhibited a potential anti-inflammatory activity by decreasing the production of NO in LPS-stimulated RAW264.7 cells. Comparative analysis of the structures of compounds 1 and 2 revealed that the acetal structure and double bond positions were the main differences between them, and these are presumed to be the main reasons for the extreme differences in their cytotoxicity and anti-inflammatory activities. From these new findings, two promising lead compounds were identified for the future development of potential anti-inflammatory or anti-tumor agents.

Development and validation of lymph node ratio-based nomograms for primary duodenal adenocarcinoma after surgery.

Background: The prediction models for primary duodenal adenocarcinoma (PDA) are deficient. This study aimed to determine the predictive value of the lymph node ratio (LNR) in PDA patients and to establish and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) for PDAs after surgical resection. Methods: We extracted the demographics and clinicopathological information of PDA patients between 2004 and 2018 from the Surveillance, Epidemiology and End Results database. After screening cases, we randomly divided the enrolled patients into training and validation groups. X-tile software was used to obtain the best cut-off value for the LNR. Univariate and multivariate Cox analyses were used in the training group to screen out significant variables to develop nomograms. The predictive accuracy of the nomograms was evaluated by the concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). Finally, four risk groups were created based on quartiles of the model scores. Results: A total of 978 patients were included in this study. The best cut-off value for the LNR was 0.47. LNR was a negative predictive factor for both OS and CSS. Age, sex, grade, chemotherapy and LNR were used to construct the OS nomogram, while age, grade, chemotherapy, the number of lymph nodes removed and LNR were incorporated into the CSS nomogram. The C-index, calibration curves and AUC of the training and validation sets revealed their good predictability. DCA showed that the predictive value of the nomograms was superior to that of the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition). In addition, risk stratification demonstrated that patients with higher risk correlated with poor survival. Conclusions: The LNR was an adverse prognostic determinant for PDAs. The nomograms provided an accurate and applicable tool to evaluate the prognosis of PDA patients after surgery.

Statistical Challenges in Tracking the Evolution of SARS-CoV-2.

Genomic surveillance of SARS-CoV-2 has been instrumental in tracking the spread and evolution of the virus during the pandemic. The availability of SARS-CoV-2 molecular sequences isolated from infected individuals, coupled with phylodynamic methods, have provided insights into the origin of the virus, its evolutionary rate, the timing of introductions, the patterns of transmission, and the rise of novel variants that have spread through populations. Despite enormous global efforts of governments, laboratories, and researchers to collect and sequence molecular data, many challenges remain in analyzing and interpreting the data collected. Here, we describe the models and methods currently used to monitor the spread of SARS-CoV-2, discuss long-standing and new statistical challenges, and propose a method for tracking the rise of novel variants during the epidemic.