Emergency rescue of a patient with hemorrhagic shock caused by superior mesenteric artery rupture: A case report.

BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

A novel compound alleviates oxidative stress via PKA/CREB1-mediated DJ-1 upregulation.

Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.

Flexible phase change film based on lignin-derived porous carbon/Eicosane for wearable thermal management and microwave absorption.

A flexible phase-change film with thermal management and microwave absorption capabilities was developed for use in wearable devices. The film was created using a solution casting method based on a porous carbon-loaded eicosane (LP33/EI) material. LP33 served as the porous encapsulation medium, while Eicosane (EI) acted as the phase change component. The flexible substrate was a blend of polyvinyl alcohol (PVA) and bacterial cellulose nanocellulose (BC). The ultrathin film had a thickness of 0.262 mm, and LP33/EI-4 exhibited exceptional mechanical strength of 188 MPa. Testing revealed that the phase transition process had melting and crystallization enthalpies of 134.71 J/g and 126.11 J/g, respectively. The encapsulation structure effectively prevented any leakage during the phase transition process. Under simulated solar irradiation of 200 mW/cm2, LP33/EI-4 achieved a photothermal conversion efficiency (η) of 89.46 %. Additionally, the porous LP33 structure and high dielectric loss contributed to remarkable microwave absorption capabilities of -42 dB in the X-band and - 52 dB in the Ku-band. Overall, LP33/EI films demonstrated exceptional performance in thermal management, energy storage, and microwave absorption, making them an ideal choice for a variety of applications in wearable devices.

Inconsistencies between prenatal diagnostic and genetic testing laboratories on variant validation of rare monogenic diseases.

BACKGROUND: The advent of next-generation sequencing (NGS) has enhanced the diagnostic efficacy for monogenic diseases, while presenting challenges in achieving consistent diagnoses. METHOD: We retrospectively analyzed the concordance rate and reasons for the inconsistency between the original diagnostic result from the genetic testing laboratory and the variant validation result from the prenatal diagnostic center. The validation procedure comprised three stages: validation of variant detection, reevaluation of variant classification, and assessment of recurrence risk, which involved verifying the mode of inheritance and parental carriage. RESULT: In total, 17 (6%) of the 286 families affected by rare monogenic diseases showed different results during the variant validation procedure. These cases comprised four (23.5%) with variant detection errors, 12 (70.5%) with inconsistent interpretation, and one (6%) with non-Mendelian inheritance patterns. False-positive NGS results confirmed by Sanger sequencing were related to pseudogenes and GC-rich regions. The classification of the 17 variants was altered in the 12 cases owing to various factors. The case with an atypical inheritance pattern was originally considered autosomal recessive inheritance, but was diagnosed as maternal uniparental disomy after additional genetic analysis. CONCLUSION: We underscored the significance of variant validation by prenatal diagnostic centers. Families affected by monogenic diseases with reproductive plans should be referred to prenatal genetic centers as early as possible to avoid different results that may postpone subsequent prenatal diagnosis.

A novel and recyclable silica gel-modified biochar to remove cadmium from wastewater: Model application and mechanism exploration.

Water pollution caused by heavy metals is a major environmental problem, threatening water production, food safety, and human health. Cadmium (Cd) pollution is particularly serious because of food-chain biomagnification at toxic concentrations. Modified biochar is promising for heavy metal removal; however, efficient adsorbents for Cd removal are lacking. In the present study, a novel adsorbent, silica gel-modified biochar (SGB), was prepared and applied to treat sewage polluted by Cd. Through the batch adsorption experiments, it is known that SGB possessed outstanding Cd removal ability and recycleability. Furthermore, the adsorption behavior and mechanisms were analyzed by the application of kinetic and isotherm models. The maximum Cd2+ adsorption capacity of SGB was 38.08 mg g-1, and after five recycling processes, the Cd2+ removal rate was still 86.89 %. When the pH of the solution was 7.0, SGB showed the strongest Cd2+ adsorption capacity (29.06 mg g-1). When competitive ions existed, biochar also had high Cd removal efficiency, although the effect of Pb2+ was greater than those of Cu2+ and Zn2+, indicating that SGB was applicable to complex polluted water. Additionally, the main Cd2+ adsorption mechanisms by SGB were electrostatic interactions, π-π interactions, complexation, and co-precipitation. These results showed that SGB can effectively treat Cd-contaminated wastewater as a new adsorbent.

Biotransformation of ginsenoside compound K using ß-glucosidase in deep eutectic solvents.

Ginsenoside compound K (CK) holds significant potential for application in the pharmaceutical industry, which exhibits numerous pharmacological activity such as cardioprotective and antidiabetic. However, the difficult separation technique and limited yield of CK hinder its widespread use. The study investigated the process of converting ginsenoside CK using ß-glucosidase. It aimed to determine the specific site where the enzyme binds and the most favorable arrangement of the enzyme. Molecular docking was also employed to determine the interaction between ß-glucosidase and ginsenosides, indicating a strong and spontaneous contact force between them. The effectiveness of the conversion process was further improved using a "green" deep eutectic solvent (DES). A univariate experimental design was used to determine the composition of DES and the optimal hydrolysis conditions for ß-glucosidase to convert ginsenoside Rb1 into ginsenoside CK. The employment of ß-glucosidase enzymatic hydrolysis in the synthesis of rare ginsenoside CK applying the environmentally friendly solvent DES is not only viable and effective but also appropriate for industrial use. The characterization methods confirmed that DES did not disrupt the structure and conformation of ß-glucosidase. In ChCl:EG = 2:1 (30%, v/v), pH 5.0 of DES buffer, reaction temperature 50 ℃, enzyme substrate mass ratio 1:1, after 36 h of reaction, the CK yield was 1.24 times that in acetate buffer, which can reach 86.2%. In this study, the process of using ß-glucosidase enzymatic hydrolysis and producing rare ginsenoside CK in green solvent DES is feasible, efficient and suitable for industrial production and application.

Advancements in research on the association between the biological CLOCK and type 2 diabetes.

Due to the Earth's rotation, the natural environment exhibits a light-dark diurnal cycle close to 24 hours. To adapt to this energy intake pattern, organisms have developed a 24-hour rhythmic diurnal cycle over long periods, known as the circadian rhythm, or biological clock. With the gradual advancement of research on the biological clock, it has become increasingly evident that disruptions in the circadian rhythm are closely associated with the occurrence of type 2 diabetes (T2D). To further understand the progress of research on T2D and the biological clock, this paper reviews the correlation between the biological clock and glucose metabolism and analyzes its potential mechanisms. Based on this, we discuss the potential factors contributing to circadian rhythm disruption and their impact on the risk of developing T2D, aiming to explore new possible intervention measures for the prevention and treatment of T2D in the future. Under the light-dark circadian rhythm, in order to adapt to this change, the human body forms an internal biological clock involving a variety of genes, proteins and other molecules. The main mechanism is the transcription-translation feedback loop centered on the CLOCK/BMAL1 heterodimer. The expression of important circadian clock genes that constitute this loop can regulate T2DM-related blood glucose traits such as glucose uptake, fat metabolism, insulin secretion/glucagon secretion and sensitivity in various peripheral tissues and organs. In addition, sleep, light, and dietary factors under circadian rhythms also affect the occurrence of T2DM.

The application of graphic language personalized emotion in graphic design.

Emotion Recognition is the experience of attitude in graphic language expression and composition. People use both verbal and non-verbal behaviours to communicate their emotions. Visual communication and graphic design are always evolving to meet the demands of an increasingly affluent and culturally conscious populace. When graphic designing works, designers should consider their own opinions about related works from the audience's or customer's standpoint so that the emotion between them can resonate. Hence, this study proposes a personalized emotion recognition framework based on convolutional neural networks (PERF-CNN) to create visual content for graphic design. Graphic designers prioritize the logic of showing objects in interactive designs and use visual hierarchy and page layout approaches to respond to users' demands via typography and imagery. This ensures that the user experience is maximized. This research identifies three tiers of emotional thinking: expressive signal, emotional experience, and emotional infiltration, all of which affect graphic design. This article explores the subject of graphic design language and its ways of emotional recognition, as well as the relationship between graphic images, shapes, and feelings. CNN initially extracted expressive features from the user's face images and the poster's visual information. The clustering process categorizes the poster or advertisement images into positive, negative, and neutral classes. Research and applications of graphic design language benefit from the proposed method's experimental results, demonstrating that it outperforms conventional classification approaches in the dataset. In comparison to other popular models, the experimental results demonstrate that the proposed PERF-CNN model improves each of the following: classification accuracy (97.4 %), interaction ratio (95.6 %), emotion recognition ratio (98.9 %), rate of influence of pattern and colour features (94.4 %), and prediction error rate (6.5 %).

Prolactin receptor potentiates chemotherapy through miRNAs-induced G6PD/TKT inhibition in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a notoriously dismal prognosis. As a competitive inhibitor of DNA synthesis, gemcitabine is the cornerstone drug for treating PDAC at all stages. The therapeutic effect of gemcitabine, however, is often hindered by drug resistance, and the underlying mechanisms remain largely unknown. It is unclear whether their response to chemotherapeutics is regulated by endocrine regulators, despite the association between PDAC risk and endocrine deregulation. Here, we show that prolactin receptor (PRLR) synergizes with gemcitabine in both in vitro and in vivo treatment of PDAC. Interestingly, PRLR promotes the expression of miR-4763-3p and miR-3663-5p, two novel miRNAs whose functions are unknown. Furthermore, the analysis of transcriptome sequencing data of tumors from lactating mouse models enriches the PPP pathway, a multifunctional metabolic pathway. In addition to providing energy, the PPP pathway mainly provides a variety of raw materials for anabolism. We demonstrate that two key enzymes of the pentose phosphate pathway (PPP), G6PD and TKT, are directly targeted by miR-4763-3p and miR-3663-5p. Notably, miR-4763-3p and miR-3663-5p diminish the nucleotide synthesis of the PPP pathway, thereby increasing gemcitabine sensitivity. As a result, PRLR harnesses these two miRNAs to suppress PPP and nucleotide synthesis, subsequently elevating the gemcitabine sensitivity of PDAC cells. Also, PDAC tissues and tumors from LSL-KrasG12D/+, LSL-Trp53R172H/+, and PDX1-cre (KPC) mice exhibit downregulation of PRLR. Bisulfite sequencing of PDAC tissues revealed that PRLR downregulation is due to epigenetic methylation. In this study, we show for the first time that the endocrine receptor PRLR improves the effects of gemcitabine by boosting two new miRNAs that block the PPP pathway and nucleotide synthesis by inhibiting two essential enzymes concurrently. The PRLR-miRNAs-PPP axis may serve as a possible therapeutic target to supplement chemotherapy advantages in PDAC.

Transcriptomic Investigation of the Virus Spectrum Carried by Midges in Border Areas of Yunnan Province.

Yunnan province in China shares its borders with three neighboring countries: Myanmar, Vietnam, and Laos. The region is characterized by a diverse climate and is known to be a suitable habitat for various arthropods, including midges which are notorious for transmitting diseases which pose significant health burdens affecting both human and animal health. A total of 431,100 midges were collected from 15 different locations in the border region of Yunnan province from 2015 to 2020. These midges were divided into 37 groups according to the collection year and sampling site. These 37 groups of midges were then homogenized to extract nucleic acid. Metatranscriptomics were used to analyze their viromes. Based on the obtained cytochrome C oxidase I gene (COI) sequences, three genera were identified, including one species of Forcipomyia, one species of Dasyhelea, and twenty-five species of Culicoides. We identified a total of 3199 viruses in five orders and 12 families, including 1305 single-stranded positive-stranded RNA viruses (+ssRNA) in two orders and seven families, 175 single-stranded negative-stranded RNA viruses (-ssRNA) in two orders and one family, and 1719 double-stranded RNA viruses in five families. Six arboviruses of economic importance were identified, namely Banna virus (BAV), Japanese encephalitis virus (JEV), Akabane virus (AKV), Bluetongue virus (BTV), Tibetan circovirus (TIBOV), and Epizootic hemorrhagic disease virus (EHDV), all of which are capable, to varying extents, of causing disease in humans and/or animals. The survey sites in this study basically covered the current distribution area of midges in Yunnan province, which helps to predict the geographic expansion of midge species. The complexity and diversity of the viral spectrum carried by midges identified in the study calls for more in-depth research, which can be utilized to monitor arthropod vectors and to predict the emergence and spread of zoonoses and animal epidemics, which is of great significance for the control of vector-borne diseases.

Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy.

Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8+ T cells (TCM) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8+ T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8+ T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44hiCD62L+CD8+ TCM cells. Enhancement of CD8+ TCM cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8+ T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8+ T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8+ TCM cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.

Assessing the safety of bedaquiline: insight from adverse event reporting system analysis.

Background: The development and marketing of Bedaquiline (BDQ) represent significant advancements in treating tuberculosis, particularly multidrug-resistant forms. However, comprehensive research into BDQ's real-world safety remains limited. Purpose: We obtained BDQ related adverse event (AE) information from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) to assess its safety and inform drug usage. Methods: The AE data for BDQ from 2012 Q4 to 2023 Q3 was collected and standardized. Disproportionality analysis, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN) was used to quantify signals of BDQ-related AEs. Logistic regression was used to analyze the individual data of hepatotoxicity and drug-induced liver injury, and multiple linear regression models were established. Additionally, network pharmacology was employed to identify the potential biological mechanisms of BDQ-induced liver injury. Results: We identified 2017 case reports directly related to BDQ. Our analysis identified 341 Preferred Terms (PTs) characterizing these AEs across 27 System Organ Classes (SOC). An important discovery was the identification of AEs associated with ear and labyrinth disorders, which had not been documented in the drug's official leaflet before. Subgroup analysis revealed a negative correlation between BDQ-related liver injury and females (OR: 0.4, 95%CI: 0.3-0.6). In addition, via network pharmacology approach, a total of 76 potential targets for BDQ related liver injury were predicted, and 11 core target genes were selected based on the characterization of protein-protein interactions. The pathway linked to BDQ-induced liver injury was identified, and it was determined that the PI3K-Akt signaling pathway contained the highest number of associated genes. Conclusion: The analysis of the FAERS database revealed adverse events linked to BDQ, prompting the use of a network pharmacology approach to study the potential molecular mechanism of BDQ-induced liver injury. These findings emphasized the significance of drug safety and offered understanding into the mechanisms behind BDQ-induced liver injury. BDQ demonstrated distinct advantages, including reduced incidence of certain adverse events compared to traditional treatments such as injectable agents and second-line drugs. However, it is important to acknowledge the limitations of this analysis, including potential underreporting and confounding factors. This study provides valuable insights into the safety of BDQ and its role in the management of MDR-TB, emphasizing the need for continued surveillance and monitoring to ensure its safe and effective use.

Cryomicroneedle delivery of nanogold-engineered Rhodospirillum rubrum for photochemical transformation and tumor optical biotherapy.

Tumor metabolite regulation is intricately linked to cancer progression. Because lactate is a characteristic metabolite of the tumor microenvironment (TME), it supports tumor progression and drives immunosuppression. In this study, we presented a strategy for antitumor therapy by developing a nanogold-engineered Rhodospirillum rubrum (R.r-Au) that consumed lactate and produced hydrogen for optical biotherapy. We leveraged a cryogenic micromolding approach to construct a transdermal therapeutic cryomicroneedles (CryoMNs) patch integrated with R.r-Au to efficiently deliver living bacterial drugs. Our long-term storage studies revealed that the viability of R.r-Au in CryoMNs remained above 90%. We found that the CryoMNs patch was mechanically strong and could be inserted into mouse skin. In addition, it rapidly dissolved after administering bacterial drugs and did not produce by-products. Under laser irradiation, R.r-Au effectively enhanced electron transfer through Au NPs actuation into the photosynthetic system of R. rubrum and enlarged lactate consumption and hydrogen production, thus leading to an improved tumor immune activation. Our study demonstrated the potential of CryoMNs-R.r-Au patch as a minimally invasive in situ delivery approach for living bacterial drugs. This research opens up new avenues for nanoengineering bacteria to transform tumor metabolites into effective substances for tumor optical biotherapy.

Self-perceived upper extremity motor function predicts health-related quality of life in chronic stroke survivors.

PURPOSE: To examine whether the Upper Extremity Functional Index (UEFI) score independently contributes to the Stroke Impact Scale (SIS) score and quantified its relative contribution to SIS scores in chronic stroke survivors. MATERIALS AND METHODS: A cross-sectional study in a university-based rehabilitation centre with people with chronic stroke (N = 95) aged ≥ 50 years. The outcome measures included paretic hand grip strength, Fugl-Meyer Upper Extremity Assessment (FMA-UE), Wolf Motor Function Test (WMFT), UEFI, and SIS. RESULTS: Correlation analysis revealed that paretic hand grip strength, FMA-UE, UEFI, and WMFT scores exhibited a significant moderate positive correlation with SIS scores (r = 0.544-0.687, p < 0.001). The results of a regression model indicated that after adjustment for demographic factors and stroke-related impairments, the UEFI scores remained independently associated with SIS scores, accounting for 18.8% of the variance. The entire model explained 60.3% of the variance in SIS scores. CONCLUSIONS: Self-perceived UE motor function is a crucial component to be included in rehabilitation programmes aimed at enhancing quality of life and participation among chronic stroke survivors.

Observation-based outcome measures, e.g., Fugl­Meyer Assessment for Upper Extremity (FMA-UE), Wolf Motor Function Test (WMFT) could not predict the health-related quality of life (Stroke Impact scale (SIS)) in chronic stroke survivors in our study, which was contradictory with current studies.A self-perceived outcome measure to evaluate upper extremity function (Upper Extremity Functional Index (UEFI)) could independently predict the health-related quality of life (SIS), accounting for 18.8% of the variance.Our study demonstrated that self-perceived UE motor function would be an important component to optimize the rehabilitation programmes aimed at enhancing quality of life and social participation among chronic stroke survivors.

Nitrification inhibitor chlorate and nitrogen substrates differentially affect comammox Nitrospira in a grassland soil.

Introduction: Through the combined use of two nitrification inhibitors, Dicyandiamide (DCD) and chlorate with nitrogen amendment, this study aimed to investigate the contribution of comammox Nitrospira clade B, ammonia oxidizing bacteria (AOB) and archaea (AOA) to nitrification in a high fertility grassland soil, in a 90-day incubation study. Methods: The soil was treated with nitrogen (N) at three levels: 0 mg-N kg-1 soil, 50 mg-N kg-1 soil, and 700 mg-N kg-1 soil, with or without the two nitrification inhibitors. The abundance of comammox Nitrospira, AOA, AOB, and nitrite oxidising bacteria (NOB) was measured using qPCR. The comammox Nitrospira community structure was assessed using Illumina sequencing. Results and Discussion: The results showed that the application of chlorate inhibited the oxidation of both NH4+ and NO2- in all three nitrogen treatments. The application of chlorate significantly reduced the abundance of comammox Nitrospira amoA and nxrB genes across the 90-day experimental period. Chlorate also had a significant effect on the beta diversity (Bray-Curtis dissimilarity) of the comammox Nitrospira clade B community. Whilst AOB grew in response to the N substrate additions and were inhibited by both inhibitors, AOA showed litle or no response to either the N substrate or inhibitor treatments. In contrast, comammox Nitrospira clade B were inhibited by the high ammonium concentrations released from the urine substrates. These results demonstrate the differential and niche responses of the three ammonia oxidising communities to N substrate additions and nitrification inhibitor treatments. Further research is needed to investigate the specificity of the two inhibitors on the different ammonia oxidising communities.

Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

Covalent binding of reactive anhydride of cantharidin to biological amines.

Cantharidin is a terpenoid from coleoptera beetles. Cantharidin has been used to treat molluscum contagiosum and some types of tumors. Cantharidin is highly toxic and cantharidin poisoning and fatal cases have been reported worldwide. The mechanisms underlying cantharidin-induced toxicity remain unclear. Cantharidin contains anhydride, which may react with biological amines. This study aimed to examine the chemical reactivity of cantharidin toward nucleophiles and characterize adducts of cantharidin with biological amines in vitro and in mice. Here, two types of conjugates were formed in the incubation of cantharidin under physiologic conditions with free amino acids, a mimic peptide, or amine-containing compounds, respectively. Amide-type conjugates were produced by the binding of cantharidin anhydride with the primary amino group of biological amines. Imide-type conjugates were generated from the dehydration and cyclization of amide-type conjugates. The structure of the conjugates was characterized by using the high-resolution mass spectrometry. We introduced the 14N/15N and 79Br/81Br isotope signatures to confirm the formation of conjugates using L-(ε)15N-lysine, L-lysine-15N2, and bromine-tagged hydrazine, respectively. The structure of imide conjugate was also confirmed by NMR experiments. Furthermore, the amide and imide conjugates of cantharidin with amino acids or N-acetyl-lysine were detected in mouse liver and urine. Cantharidin was found to modify lysine residue proteins in mouse liver. Pan-P450 inhibitor 1-aminobenzotriazole significantly increased the urine cantharidin-N-acetyl-lysine conjugates whereas decreased cantharidin metabolites. In summary, cantharidin anhydride can covalently bind to biological amines nonenzymatically, which facilitates a better understanding of the role of nonenzymatic reactivity in cantharidin poisoning. Significance Statement Anhydride moiety of cantharidin can covalently bind to the primary amino group of biological amines nonenzymatically. Amide and imide conjugates were generated after the covalent binding of cantharidin anhydride with the primary amino groups of amino acids, a mimic peptide, and protein lysine residues. The structure of conjugates was confirmed by 14N/15N and 79Br/81Br isotope signatures using isotope-tagged reagents and NMR experiments. This study will facilitate the understanding of the role of nonenzymatic reactivity in cantharidin poisoning.

Higher diversity of sulfur-oxidizing bacteria based on soxB gene sequencing in surface water than in spring in Wudalianchi volcanic group, NE China.

INTRODUCTION: Sulfur-oxidizing bacteria (SOB) play a key role in the biogeochemical cycling of sulfur. OBJECTIVES: To explore SOB diversity, distribution, and physicochemical drivers in five volcanic lakes and two springs in the Wudalianchi volcanic field, China. METHODS: This study analyzed microbial communities in samples via high-throughput sequencing of the soxB gene. Physical-chemical parameters were measured, and QIIME 2 (v2019.4), R, Vsearch, MEGA7, and Mothur processed the data. Alpha diversity indices and UPGMA clustering assessed community differences, while heat maps visualized intra-sample variations. Canoco 5.0 analyzed community-environment correlations, and NMDS, Adonis, and PcoA explored sample dissimilarities and environmental factor correlations. SPSS v.18.0 tested for statistical significance. RESULTS: The diversity of SOB in surface water was higher than in springs (more than 7.27 times). We detected SOB affiliated to ß-proteobacteria (72.3 %), α-proteobacteria (22.8 %), and γ-proteobacteria (4.2 %) distributed widely in these lakes and springs. Rhodoferax and Cupriavidus were most frequent in all water samples, while Rhodoferax and Bradyrhizobium are dominant in surface waters but rare in springs. SOB genera in both habitats were positively correlated. Co-occurrence analysis identified Bradyrhizobium, Blastochloris, Methylibium, and Metyhlobacterium as potential keystone taxa. Redundancy analysis (RDA) revealed positive correlations between SOB diversity and total carbon (TC), Fe2+, and total nitrogen (TN) in all water samples. CONCLUSION: The diversity and community structure of SOB in volcanic lakes and springs in the Wudalianchi volcanic group were clarified. Moreover, the diversity and abundance of SOB decreased with the variation of water openness, from open lakes to semi-enclosed lakes and enclosed lakes.