The association between serum methylmalonic acid, cobalamin-related biomarkers, and long-term mortality risk in cancer survivors: a prospective cohort study.

BACKGROUND: Elevated serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, has been linked to cancer progression. However, the impact of MMA or cobalamin on mortality risk in cancer survivors remains unknown. OBJECTIVES: To explore the relationship between MMA, serum, dietary, and supplement of cobalamin, MMA metabolism-related genes, and poor prognosis in adult cancer survivors. METHODS: We analyzed data from 1988 cancer survivors aged ≥20 y. Patients were selected from the National Health and Nutrition Examination Survey and followed up until December 31, 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for mortality risk assessment. Genomic analysis identified MMA metabolism-related genes linked to early death in a 33-cancer-type cohort from The Cancer Genome Atlas. RESULTS: Among 1988 participants, 872 deaths occurred over a 10-year follow-up. Higher serum MMA levels were significantly linked to increased long-term mortality risk (tertile 3 compared with tertile 1: adjusted HR: 1.37; 95% CI: 1.11, 1.70; P-trend < 0.001). No associations were found between serum, dietary, and supplement of cobalamin and cancer survivor mortality (each P-trend > 0.143). However, MMA-associated mortality was notable in patients without deficiency. When combining cobalamin and MMA categories, multivariate-adjusted HR (95% CI) for all-cause mortality was 2.06 (95% CI: 1.60, 2.65) in participants with >250 nmol/L and cobalamin >295.1 pmol/L compared with those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L. Moreover, reduced transcriptional levels of MMA metabolism-related genes, indicating decreased mitochondrial MMA metabolism capability, are linked to an unfavorable prognosis in certain cancer types. CONCLUSIONS: Serum MMA was associated with long-term mortality risk in adult cancer survivors, which was more significant among individuals with higher levels of serum cobalamin. These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency.

Decreased cobalamin sensitivity and biological aging acceleration in the general population.

BACKGROUND: The evidence on the association between cobalamin (Cbl) and aging or relevant outcomes is limited and controversial. We aimed to investigate the relationships between cobalamin intake- and function-related biomarkers and biological aging. METHODS: The study encompassed 22,812 participants aged 20 years and older from the National Health and Nutrition Examination Survey. A panel of biomarkers or algorithms was used to assess biological aging, including Klemera-Doubal Age Acceleration (KDMAccel), Phenotypic age acceleration (PhenoAgeAccel), telomere length, α-Klotho, and PhenoAge advancement. Weighted generalized linear regression analysis was used to assess the associations between cobalamin-intake biomarkers (serum cobalamin, cobalamin intake from food, cobalamin supplement use, serum methylmalonic acid [MMA], and homocysteine [Hcy]) and function-related biomarkers (functional cobalamin deficiency and cobalamin insensitivity index). RESULTS: Among the 22,812 individuals, the weighted mean (SE) age was 48.3 (0.2) years and 48.0% were males. Unexpectedly, serum and dietary cobalamin as well as serum MMA and Hcy levels were positively associated with most indicators of biological aging. Cobalamin sensitivity was assessed by the combination of binary Cbllow/high and MMAlow/high or Hcylow/high (cutoff values: 400 pg/mL for cobalamin, 250 nmol/L for MMA, and 12.1 µmol/l for Hcy) and a newly constructed cobalamin insensitivity index (based on the multiplicative term of serum cobalamin and serum MMA or Hcy). The multivariable-adjusted ß (95%CIs) of KDMAccel in the MMAlowCbllow, MMAlowCblhigh, MMAhighCbllow, and MMAhighCblhigh groups were reference, 0.27 (0.03 to 0.51), 0.85 (0.41 to 1.29), and 7.97 years (5.77 to 10.17) respectively, which were consistent for the combination of serum Hcy and cobalamin. Both cobalamin insensitivity indices were robustly associated with biological aging acceleration in a dose-response pattern (each p < 0.001). CONCLUSIONS: Decreased cobalamin sensitivity but not cobalamin insufficiency might be associated with biological aging acceleration. Further studies would improve understanding of the underlying mechanisms between decreased cobalamin sensitivity and biological aging acceleration.

BRD4 promotes gouty arthritis through MDM2-mediated PPARγ degradation and pyroptosis.

BACKGROUND: Gouty arthritis (GA) is characterized by monosodium urate (MSU) crystal accumulation that instigates NLRP3-mediated pyroptosis; however, the underlying regulatory mechanisms have yet to be fully elucidated. The present research endeavors to elucidate the regulatory mechanisms underpinning this MSU-induced pyroptotic cascade in GA. METHODS: J774 cells were exposed to lipopolysaccharide and MSU crystals to establish in vitro GA models, whereas C57BL/6 J male mice received MSU crystal injections to mimic in vivo GA conditions. Gene and protein expression levels were evaluated using real-time quantitative PCR, Western blotting, and immunohistochemical assays. Inflammatory markers were quantified via enzyme-linked immunosorbent assays. Pyroptosis was evaluated using immunofluorescence staining for caspase-1 and flow cytometry with caspase-1/propidium iodide staining. The interaction between MDM2 and PPARγ was analyzed through co-immunoprecipitation assays, whereas the interaction between BRD4 and the MDM2 promoter was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. Mouse joint tissues were histopathologically evaluated using hematoxylin and eosin staining. RESULTS: In GA, PPARγ was downregulated, whereas its overexpression mitigated NLRP3 inflammasome activation and pyroptosis. MDM2, which was upregulated in GA, destabilized PPARγ through the ubiquitin-proteasome degradation pathway, whereas its silencing attenuated NLRP3 activation by elevating PPARγ levels. Concurrently, BRD4 was elevated in GA and exacerbated NLRP3 activation and pyroptosis by transcriptionally upregulating MDM2, thereby promoting PPARγ degradation. In vivo experiments showed that BRD4 silencing ameliorated GA through this MDM2-PPARγ-pyroptosis axis. CONCLUSION: BRD4 promotes inflammation and pyroptosis in GA through MDM2-mediated PPARγ degradation, underscoring the therapeutic potential of targeting this pathway in GA management.

Research progress on the mechanism of TCM regulating intestinal microbiota in the treatment of DM mellitus.

In recent years, with the improvement of people's living standards, the incidence of DM has increased year by year in China. DM is a common metabolic syndrome characterized by hyperglycemia caused by genetic, environmental and other factors. At the same time, long-term suffering from DM will also have an impact on the heart, blood vessels, eyes, kidneys and nerves, and associated serious diseases. The human body has a large and complex gut microbiota, which has a significant impact on the body's metabolism. Research shows that the occurrence and development of DM and its complications are closely related to intestinal microbiota. At present, western medicine generally treats DM with drugs. The hypoglycemic effect is fast and strong, but it can have a series of side effects on the human body. Compared with western medicine, Chinese medicine has its unique views and methods in treating DM. TCM can improve symptoms and treat complications by improving the imbalance of microbiota in patients with DM. Its characteristics of health, safety, and reliability are widely accepted by the general public. This article reviews the relationship between intestinal microbiota and DM, as well as the mechanism of TCM intervention in DM by regulating intestinal microbiota.

Cost-related medication nonadherence in adults with COPD in the United States 2013-2020.

BACKGROUND: Cost-related medication nonadherence (CRN) is associated with poor prognosis among patients with chronic obstructive pulmonary disease (COPD), a population that requires long-term treatment for secondary prevention. In this study, we aimed to estimate the prevalence and sociodemographic characteristics of CRN in individuals with COPD in the US. METHODS: In a nationally representative survey of US adults in the National Health Interview Survey (2013-2020), we identified individuals aged ≥18 years with a self-reported history of COPD. Cross-sectional study. RESULTS: Of the 15,928 surveyed individuals, a weighted 18.56% (2.39 million) reported experiencing CRN, including 12.50% (1.61 million) missing doses, 13.30% (1.72 million) taking lower than prescribed doses, and 15.74% (2.03 million) delaying filling prescriptions to save costs. Factors including age < 65 years, female sex, low family income, lack of health insurance, and multimorbidity were associated with CRN. CONCLUSIONS: In the US, one in six adults with COPD reported CRN. The influencing factors of CRN are multifaceted and necessitating more rigorous research. Targeted interventions based on the identified influencing factors in this study are recommended to enhance medication adherence among COPD patients.

Mechanisms of microRNA-132 in central neurodegenerative diseases: A comprehensive review.

MicroRNA-132 (miR-132) is a highly conserved molecule that plays a crucial regulatory role in central nervous system (CNS) disorders. The expression levels of miR-132 exhibit variability in various neurological disorders and have been closely linked to disease onset and progression. The expression level of miR-132 in the CNS is regulated by a diverse range of stimuli and signaling pathways, including neuronal migration and integration, dendritic outgrowth, and complexity, synaptogenesis, synaptic plasticity, as well as inflammation and apoptosis activation. The aberrant expression of miR-132 in various central neurodegenerative diseases has garnered widespread attention. Clinical studies have revealed altered miR-132 expression levels in both chronic and acute CNS diseases, positioning miR-132 as a potential biomarker or therapeutic target. An in-depth exploration of miR-132 holds the promise of enhancing our understanding of the mechanisms underlying CNS diseases, thereby offering novel insights and strategies for disease diagnosis and treatment. It is anticipated that this review will assist researchers in recognizing the potential value of miR-132 and in generating innovative ideas for clinical trials related to CNS degenerative diseases.

[Effect of High-Concentration Uric Acid on Nitric Oxide].

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.

Trends in Electronic Cigarette Use Among US Adults With a History of Cardiovascular Disease.

This cross-sectional study analyzes the prevalence of electronic cigarette (e-cigarette) use among adults with cardiovascular disease in the US between 2014 and 2020.

Deubiquitinase USP16 induces gouty arthritis via Drp1-dependent mitochondrial fission and NLRP3 inflammasome activation.

BACKGROUND: Gouty arthritis is the most frequently diagnosed inflammatory arthritis worldwide. Dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, contributes to various inflammatory disorders via activating NLRP3 inflammasome. However, the biological role of Drp1 in gouty arthritis remains undefined. METHODS: A mouse model of monosodium urate (MSU)-induced gouty arthritis and MSU-stimulated macrophages were established as in vivo and in vitro models, respectively. Histological changes were assessed by H&E and IHC analysis. RT-qPCR and western blot were used to detect the expression of Drp1 and the key molecules in joint tissues and macrophages. Cytokine secretion was measured by ELISA assay, and antioxidant enzymes activities and LDH release were monitored using commercial kits. Mitochondrial structure and functions were assessed by transmission electron microscopy (TEM) and MitoSOX staining. Co-IP and GST pull-down assay were used to detect the direct interaction between USP16 and Drp1, as well as the ubiquitination of Drp1. RESULTS: Drp1 was elevated in MSU-induced gouty arthritis model, and it induced gouty arthritis via NF-κB pathway and NLRP3 inflammasome activation. In addition, Drp1 activated NF-κB/NLRP3 signaling via modulating mitochondrial fission. Mechanistically, USP16 mediated deubiquitination and stabilization of Drp1 through its direct interaction with Drp1. Functional studies further showed that USP16 was highly expressed in MSU-stimulated macrophages and induced gouty arthritis via Drp1-dependent NLRP3 inflammasome activation. CONCLUSION: Deubiquitinase USP16 induced gouty arthritis via Drp1-dependent mitochondrial fission and NF-κB/NLRP3 signaling.

Cost-related medication nonadherence in US adults with asthma: The National Health Interview Survey, 2013-2020.

BACKGROUND: Asthma is a chronic disease that needs long-term control for secondary prevention. Health-related expenditures resulting from asthma are rising in the United States, and medication nonadherence is associated with adverse health outcomes in patients with asthma. OBJECTIVE: To estimate the prevalence and risk factors of cost-related medication nonadherence (CRN) in individuals with asthma in the United States. METHODS: We identified patients aged above or equal to 18 years with a history of asthma in nationally representative cross-sectional data, the National Health Interview Survey 2013 to 2020. Participants were considered to have experienced CRN if at any time in the 12 months they reported skipping doses, taking less medication, or delaying filling a prescription to save money. The weighted prevalence of CRN was estimated overall and by subgroups. Logistic regression was used to identify CRN-related characteristics. RESULTS: Of the 26,539 National Health Interview Survey participants with a history of asthma, 4360 (15.77%; representing 3.92 million of the US population) reported CRN, with 10.12% (weighted 2.51 million) of patients skipping doses to save money, 10.82% (weighted 2.69 million) taking less medication to save money, and 13.35% (weighted 3.31 million) delaying filling a prescription to save money. The subgroups young, women, low income, no health insurance, currently smoking, and with comorbidities had a higher prevalence of CRN. The results of this sensitivity analysis did not differ from the overall results. CONCLUSION: In the United States, 1 in 6 adults with a history of asthma is nonadherence with medications due to costs. Removing financial barriers to accessing medication can improve medication adherence in patients with asthma.

The association between sarcopenia and incident chronic lung disease in the general population: A longitudinal study based on CHARLS data.

BACKGROUND: Data regarding the association of sarcopenia with chronic lung disease (CLD) has led to inconclusive results. The main goal of this research was to investigate the association between sarcopenia and CLD in middle-aged and elderly individuals in China. METHODS: The study sample consisted of 11,077 individuals without CLD at baseline chosen from the China Health and Retirement Longitudinal Study (CHARLS) data from 2015, followed up until 2018. Sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia (AWGS 2019) in 2019. Individuals were categorized into no-sarcopenia, possible-sarcopenia, and sarcopenia groups. The outcome of the study was considered to be incident CLD, which included chronic bronchitis, emphysema, pulmonary heart disease, and asthma. The association between sarcopenia and the risk of CLD was also examined by employing weighted Cox proportional hazard regression models. RESULTS: A total of 356 (3.20 %) participants developed CLD during the 3.6-year follow-up period. The cumulative incidence of CLD in the no-sarcopenia, possible-sarcopenia, and sarcopenia groups was 2.80 % (230/8222), 4.37 % (55/1260), and 4.45 % (71/1595), respectively. Individuals with possible sarcopenia {hazard ratio [HR] [95 % confidence interval (CI)]: 1.48 [1.04-2.09]} and sarcopenia [HR (95 % CI): 1.68 (1.12-2.51)] demonstrated a considerably high risk of developing CLD compared to individuals in the no-sarcopenia group. Moreover, individuals diagnosed with sarcopenia, as per the criteria established by the European Working Group on Sarcopenia in Older People (EWGSOP) 2018, were at considerably high risk for developing CLD compared to those in the no-sarcopenia group. CONCLUSION: This research involving adult Chinese individuals demonstrated a significant association between, possible sarcopenia and sarcopenia with an elevated risk of incident CLD, thereby emphasizing the importance of monitoring respiratory health in this population. KEY POINTS: Question: Whether muscle mass and sarcopenia are associated with the development of chronic lung disease (CLD) in Asian middle-aged and elderly individuals. FINDINGS: This longitudinal study encompassing 11,077 adults aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS) data with 3.6 years of follow-up revealed a positive association between sarcopenia at baseline and incidence of CLD. Meaning: The findings suggest that possible sarcopenia and sarcopenia are linked to the development of CLD. Consequently, middle-aged and elderly individuals with possible sarcopenia and sarcopenia can be considered vulnerable regarding the primary prevention strategies for CLD.

Prognosis and surgical outcomes of the total thymectomy versus thymomectomy in non-myasthenic patients with early-stage thymoma: A systematic review and meta-analysis.

Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical outcomes and prognoses of non-myasthenic patients with early-stage thymoma treated using thymectomy versus thymomectomy. PubMed, Embase, Cochrane Library and CNKI databases were systematically searched for relevant studies on the surgical treatment (TM and TMM) of non-myasthenic patients with early-stage thymoma published before March 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the studies, and the data were analyzed using RevMan version 5.30. Fixed or random effect models were used for the meta-analysis depending on heterogeneity. Subgroup analyses were performed to compare short-term perioperative and long-term tumor outcomes. A total of 15 eligible studies, including 3023 patients, were identified in the electronic databases. Our analysis indicated that TMM patients might benefit from a shorter duration of surgery (p = 0.006), lower blood loss volume (p < 0.001), less postoperative drainage (p = 0.03), and a shorter hospital stay (p = 0.009). There were no significant differences in the overall survival rate (p = 0.47) or disease-free survival rate (p = 0.66) between the two surgery treatment groups. Likewise, TM and TMM were similar in the administration of adjuvant therapy (p = 0.29), resection completeness (p = 0.38), and postoperative thymoma recurrence (p = 0.99). Our study revealed that TMM might be a more appropriate option in treating non-myasthenic patients with early-stage thymoma.

L-shaped association between dietary zinc intake and the risk of developing cardiovascular disease in Chinese adults: A cohort study.

Background: Although the association of zinc (Zn) with cardiovascular disease (CVD) has been studied, no consensus has been reached on this relationship, particularly dietary Zn intake. The purpose of this study was to assess the effect of dietary Zn intake on the risk of CVD and to analyze whether this effect varied according to zinc consumption using representative data from China. Methods: 11,470 adults from the China Health and Nutrition Survey (CHNS) were eventually enrolled. The dietary information was collected by the 3 day 24-h dietary recalls combined with dietary weighting method. CVD was defined as participants with self-reported physician-diagnosed apoplexy and/or myocardial infarction during the follow-up. Cox regression was used to calculate the hazard ratios (HRs) of CVD with 95% confidence intervals. Restricted cubic spline function plus Cox regression was used to visualize the influence trend of dietary Zn intake on new-onset CVD and to test whether this trend is linear. 2-segment Cox regression was established to address the nonlinear trend. Results: 431 participants developed CVD, including 262 strokes and 197 myocardial infarctions. Compared with the lowest quintile (Q1), the adjusted hazard ratios and 95% confidence interval (CI) of CVD in Q2 to Q5 of dietary Zn intake were 0.72 (0.54, 0.97), 0.59 (0.42, 0.81), 0.50 (0.34, 0.72) and 0.44 (0.27, 0.71), respectively. The influence trend of dietary Zn intake on new-onset CVD was nonlinear and L-shaped. When dietary Zn intake <13.66 mg/day, increased dietary Zn intake was significantly associated with decreased risk of developing CVD (HR = 0.87, 95% CI: 0.82-0.92, p-value <0.0001). Conclusion: An L-shaped trend was observed between dietary Zn intake and the risk of developing CVD, indicating that dietary Zn intake should be improved moderately, but not excessively, for the benefit of cardiovascular disease.

Recognition of spider mite infestations in jujube trees based on spectral-spatial clustering of hyperspectral images from UAVs.

Spider mite infestations are a serious hazard for jujube trees in China. The use of remote sensing technology to evaluate the health of jujube trees in large-scale intensive agricultural production is an effective means of agricultural control. Hyperspectral remote sensing has a higher spectral resolution and richer spectral information than conventional multispectral remote sensing, which improves the detection of crop pests and diseases. We used hyperspectral remote sensing data from jujube fields infested with spider mite in Hotan Prefecture, Xinjiang to evaluate their use in monitoring this important pest. We fused spectral and spatial information from the hyperspectral images and propose a method of recognizing spider mite infestations of jujube trees. Our method is based on the construction of spectral features, the fusion of spatial information and clustering of these spectral-spatial features. We evaluated the effect of different spectral-spatial features and different clustering methods on the recognition of spider mite in jujube trees. The experimental results showed that the overall accuracy of the method for the recognition of spider mites was >93% and the overall accuracy of the band clustering-density peak clustering model for the recognition of spider mite reached 96.13%. This method can be applied to the control of jujube spider mites in agricultural production.

[Corrigendum] Decreased RNA­binding protein IGF2BP2 downregulates NT5DC2, which suppresses cell proliferation, and induces cell cycle arrest and apoptosis in diffuse large B­cell lymphoma cells by regulating the p53 signaling pathway.

Subsequently to the publication of this paper, the authors have realized that they included the incorrect data in Fig. 5 for the p21 blots on p. 8. The corrected version of Fig. 5, featuring the data that were intended to have been included in this figure for the p21 blots, is shown on the next page.  Furthermore, the authors wish to make the following changes to the text in the paper (changes are highlighted in bold): i) on p. 2, left­hand column, line 16, the final sentence in the penultimate paragraph of the Introduction should have read as: "However, the functions of RNA­binding protein (RBP) IGF2BP2, and the interactions between IGF2BP2 and NT5DC2 in DLBCL remain to be explored."; ii) In the Materials and methods section, subsection "RNA pull­down assay", the first sentence should be revised to: "An RNA pull down kit (cat. no. P0202: Geneseed) was used to perform RNA pull down assay according to the manufacturer's instructions."; iii) In the Results section on p. 3, the subsection "NT5DC2 is upregulated in DLBC cells and knockdown of NT5DC2 inhibits proliferation of DLBC cells.", the second sentence should be revised as follows: "mRNA and protein expression of NT5DC2 was highest in OCI­Ly7 cells compared with that in the other DLBC cell lines (Fig. 1A)."; iv) The first two sentences in the following paragraph should have read as follows: "mRNA and protein expression levels of NT5DC2 were decreased in DLBC cells transfected with shRNA­NT5DC2#1/2 compared with the untransfected group, and were lower in the shRNA­NT5DC2#2 group compared with the shRNA­NT5DC2#1 group (Fig. 1B)."; and v) On p. 7, left­hand column, the sentence commencing on line 59 should have read as: "The present results indicated that NT5DC2 was increased in DLBCL cells...". Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree with the publication of this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 26: 286, 2022; DOI: 10.3892/mmr.2022.12802].

Factors influencing surgical choice and anxiety in patients with pulmonary nodules smaller than 8 mm.

Background: The detection of pulmonary nodules significantly impacts the lives and mental health of patients. Although the 2020 National Comprehensive Cancer Network (NCCN) guidelines recommend scheduled surveillance for nodules ≤8 mm, patients often opt to have their nodules surgically removed. Methods: A cross-sectional questionnaire was administered to patients with small pulmonary nodules who presented to a local grade 3 hospital with small pulmonary nodules and decided to receive surgery versus prescribed monitoring. The questionnaire included four aspects: (I) patient characteristics; (II) nodule-specific knowledge; (III) doctor-patient communication; and (IV) nodular-specific distress. Nodular-specific distress was measured by the Impact of Event Scale-Revised (IES-R). Results: A total of 234 (69%) patients responded to the survey and were included in the final analysis. Poor performance in activities of daily living (ADLs), the presence of solid nodules, multifocal disease, and a family history of lung cancer were significantly associated with reported anxiety. Most notably, facilitating patient choice for surgery was the computed tomography (CT) scan results, with reference to lung nodule size and number of nodules, where concerns related to lung nodule, cancer risk, and fear of surgery or death had a significant psychological impact on patients. Conclusions: In this cohort of patients who elected to have their small pulmonary nodules surgically removed, we identified key factors underlying their anxiety toward guideline recommended surveillance. Our findings will be useful for clinicians when discussing treatment options with their patients.

Mechanism of PDZK1 in Hepatocellular Carcinoma Complicated with Hyperuricemia.

Background: Hepatocellular carcinoma (HCC) is a kind of primary liver cancer that accounts for more than 90% of primary hepatocellular carcinomas. Hyperuricemia is closely related to the development, recurrence, metastasis, and prognosis of cancer. Previous studies have proved that the serum uric acid level can increase the incidence rate and mortality of malignant tumors. However, the specific pathogenesis remains unstudied. Methods: RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after HCC cells were exposed to different concentrations of soluble uric acid (2.5, 5, 10, 20 mg/dl) for 24 hours. Then, in HCC shRNAs, PDZK1, or over expression PDZK1 were used. CCK8, wound healing, and Transwell assay showed that PDZK1 regulates cell proliferation, invasion, and migration. Flow cytometry results revealed that PDZK1 affects cell apoptosis. Western blot results show that PDZK1 affects the STAT3/C-myc pathway. Then, in vivo tumorigenesis, allopurinol maybe an effective drug to advance: the prognosis of HCC. Results: In our study, RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after different concentrations of soluble uric acid in HCC. Then, PDZK1 affects the proliferation, migration, and apoptosis of HCC through the STAT3/C-myc pathway. Conclusions: Hyperuricemia response affects the expression of PDZK1; PDZK1 affects the proliferation, migration, and apoptosis through the STAT3/C-myc pathway in hepatocellular carcinoma. It is suggested that PDZK1 maybe closely related to the occurrence, development, and prognosis of HCC and allopurinol maybe have potential anticancer effects.

Inversion of chlorophyll content under the stress of leaf mite for jujube based on model PSO-ELM method.

During the growth season, jujube trees are susceptible to infestation by the leaf mite, which reduces the fruit quality and productivity. Traditional monitoring techniques for mites are time-consuming, difficult, subjective, and result in a time lag. In this study, the method based on a particle swarm optimization (PSO) algorithm extreme learning machine for estimation of leaf chlorophyll content (SPAD) under leaf mite infestation in jujube was proposed. Initially, image data and SPAD values for jujube orchards under four severities of leaf mite infestation were collected for analysis. Six vegetation indices and SPAD value were chosen for correlation analysis to establish the estimation model for SPAD and the vegetation indices. To address the influence of colinearity between spectral bands, the feature band with the highest correlation coefficient was retrieved first using the successive projection algorithm. In the modeling process, the PSO correlation coefficient was initialized with the convergent optimal approximation of the fitness function value; the root mean square error (RMSE) of the predicted and measured values was derived as an indicator of PSO goodness-of-fit to solve the problems of ELM model weights, threshold randomness, and uncertainty of network parameters; and finally, an iterative update method was used to determine the particle fitness value to optimize the minimum error or iteration number. The results reflected that significant differences were observed in the spectral reflectance of the jujube canopy corresponding with the severity of leaf mite infestation, and the infestation severity was negatively correlated with the SPAD value of jujube leaves. The selected vegetation indices NDVI, RVI, PhRI, and MCARI were positively correlated with SPAD, whereas TCARI and GI were negatively correlated with SPAD. The accuracy of the optimized PSO-ELM model (R 2 = 0.856, RMSE = 0.796) was superior to that of the ELM model alone (R 2 = 0.748, RMSE = 1.689). The PSO-ELM model for remote sensing estimation of relative leaf chlorophyll content of jujube shows high fault tolerance and improved data-processing efficiency. The results provide a reference for the utility of UAV remote sensing for monitoring leaf mite infestation of jujube.

Folic acid and zinc improve hyperuricemia by altering the gut microbiota of rats with high-purine diet-induced hyperuricemia.

A high-purine diet can cause hyperuricemia and destroy the microbial composition of the gut microbiota. Both folic acid and zinc significantly reduce uric acid levels and alleviate hyperuricemia. However, whether the underlying mechanisms are associated with the regulation of the gut microbiota remain unknown. To explore alterations of the gut microbiota related to folic acid and zinc treatment in rats with hyperuricemia in our study. A hyperuricemic rat model was established with a high-purine diet. The effects of folic acid and zinc on uric acid levels were evaluated. Alterations of the gut microbiota related to hyperuricemia and the treatments were evaluated by sequencing using the Illumina MiSeq system. The results demonstrated that uric acid levels dropped observably, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) were downregulated after folic acid or zinc intervention. 16S rRNA gene sequencing-based gut microbiota analysis revealed that folic acid and zinc enhanced the abundance of probiotic bacteria and reduced that of pathogenic bacteria, thus improving intestinal barrier function. PICRUST analysis indicated that folic acid and zinc restored gut microbiota metabolism. These findings indicate that folic acid and zinc ameliorate hyperuricemia by inhibiting uric acid biosynthesis and stimulating uric acid excretion by modulating the gut microbiota. Thus, folic acid and zinc may be new and safe therapeutic agents to improve hyperuricemia.