Optimization of preparation conditions for ß-chitosan derived from diatom biomanufacturing using response surface methodology.

Chitosan is a polymeric polysaccharide with widely application. At present, commercialized chitosan obtained by deacetylating chitin with acid-alkali method. The homogeneity of the molecular weight of chitosan is difficult to adjust due to the low homogeneity of chitosan itself and the degradation effect of the extraction process. And the single source of raw material has limited the further development of chitosan. In this study, diatoms were used as the source of chitosan extraction through alkalization freeze-thaw method, and response surface methodology was also used to optimize the best preparation conditions of diatom chitosan. The extracted chitosan from diatom was ß-type chitosan with low molecular weight, great homogeneity. Diatom chitosan was able to reduce blood loss and clotting time >30 % in vivo experiment compared to control. The hemolysis rate of diatom chitosan was lower than 1 %, and the survival rate was higher than 95 % when co-cultured with L929 cells. Diatom chitosan with 0.005 % could inhibit E. coli and S. aureus by >90 %. Considering the large-scale cultivation properties of diatom, the extraction of diatom chitosan based on alkalization freeze-thaw method will provide a viable solution for obtaining ß-chitosan with homogeneity on a large scale.

ATG10-dependent autophagy is required for DDX10 to regulate cell proliferation, apoptosis and stemness in colorectal cancer.

Colorectal cancer (CRC) remains a highly prevalent gastrointestinal neoplasm, presenting significant prevalence and lethality rate. DEAD/H box RNA helicase 10 (DDX10) has been proposed as a potential oncogene in CRC, the specific action mechanism by which DDX10 modulates the aggressive biological cellular events in CRC remains implicitly elucidated, however. During this study, DDX10 expression was detected via RT-qPCR and Western blotting. Cell proliferation was estimated via EDU staining. TUNEL staining and Western blotting appraised cell apoptosis. Cell stemness was evaluated by sphere formation assay, RT-qPCR, Western blotting as well as immunofluorescence staining. Relevant assay kit examined aldehyde dehydrogenase (ALDH) activity. Western blotting and immunofluorescence staining also detected autophagy. DDX10 was hyper-expressed in CRC cells. Down-regulation of DDX10 hampered cell proliferation, aggravated the apoptosis while eliminated the ability to form spheroid cells in CRC. In addition, DDX10 deletion improved ATG10 expression and therefore activated autophagy in CRC cells. Consequently, ATG10 depletion or treatment with autophagy inhibitor 3-Methyladenine (3-MA) partially compensated the influences of DDX10 silencing on the proliferation, apoptosis and stemness of CRC cells. Accordingly, DDX10 deficiency may aggravate autophagy mediated by ATG10 to impede cell proliferation, stemness and facilitate cell apoptosis, hence blocking the progression of CRC.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults.

BACKGROUND: Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. OBJECTIVES: We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS: In this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS: Among 305 participants (median age: 50 y, IQR, 37-59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (ß = -0.013, P < 0.001) and body fat mass (ß= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (ß = -0.040, P = 0.011). CONCLUSIONS: High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Associations between adverse childhood experiences and pain in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Effects of deep coal mining on groundwater hydrodynamic and hydrochemical processes in a multi-aquifer system: Insights from a long-term study of mining areas in ecologically fragile western China.

The groundwater hydrodynamic and hydrochemical process of the multi-aquifer system will experience complicated and serious influence under deep coal mining disturbance. There is relatively little research that has integrated hydrodynamic and hydrochemical properties of groundwater to investigate the spatiotemporal distribution characteristics and evolution patterns of hydrogeochemistry and hydrodynamic information in deep multi-aquifer systems. The study of the groundwater hydrodynamic and hydrochemical spatiotemporal coupling response of multi-aquifer systems under the deep and special thick coal seam mining-motivated effect in ecologically fragile western mining areas is of great significance for the safe mining of coal resources and ecological environment protection. In this research, the hydrochemical analysis data composed of 218 groundwater samples from Tangjiahui coalfield, Northwest China with 1526 measurements and a 6-year (2016-2021) sampling period were collected for studying the hydrogeochemical spatiotemporal evolution process and governing mechanism of the multi-aquifer system using hierarchical cluster analysis, ion-ratio method, saturation index and multidimensional statistical analysis. Additionally, wavelet analysis and cross-wavelet coherence analysis were implemented to quantitatively recognize the spatiotemporal variation characteristics of hydrodynamic information and analyze the coherence relationships between time series. The results demonstrate that the hydrochemical characteristics exhibit significant spatial differences, while the temporal variation of hydrochemical characteristics in the Permian Shanxi Formation fractured sandstone aquifer (PSFFA), mine water (MW), and Ordovician karst limestone aquifer (OKA) is not significant. The water-rock interaction is the predominant control mechanism for the spatial evolution of hydrogeochemistry in the research area. Moreover, the large-scale mining of deep coal seams controls the type and degree of water-rock interactions by damaging the structure of aquifers and altering the hydrodynamic conditions of groundwater. The period from 2016 to 2021 exhibits multi-time scale characteristics in time series of precipitation, mine water discharge, and the water level of PSFFA and OKA. The mine water discharge has a positive correlation with the water level of PSFFA and OKA, whereas the significant period of precipitation and the water level of PSFFA coherence is not obvious. The research findings not only provide in-depth insights to protect the groundwater resources in water-shortage mining areas but also promote the secure mining of deep coal resources.

Global responses of wetland methane emissions to extreme temperature and precipitation.

As global warming continues, events of extreme heat or heavy precipitation will become more frequent, while events of extreme cold will become less so. How wetlands around the globe will react to these extreme events is unclear yet critical, because they are among the greatest natural sources of methane(CH4). Here we use seven indices of extreme climate and the rate of methane emission from global wetlands(WME) during 2000-2019 simulated by 12 published models as input data. Our analyses suggest that extreme cold (particularly extreme low temperatures) inhibits WME, whereas extreme heat (particularly extreme high temperatures) accelerates WME. Our results also suggest that daily precipitation >10 mm accelerates WME, while much higher daily precipitation levels can slow WME. The correlation of extreme high temperature and precipitation with rate of WME became stronger during the study period, while the correlation between extreme low temperature and WME rate became weaker.

Favorable Outcomes of Liver Transplantation for Hepatopulmonary Syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. METHODS: Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. RESULTS: Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P = .003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P = .001). CONCLUSION: Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS.

Body Composition Indicators Jointly Predict Metabolic Unhealthy Phenotypes in Young and Middle-Aged Obese Individuals: A Cross-Sectional Quantitative Computed Tomography Study.

Purpose: The main aim of this study is to analyze the relationship between body composition indices and metabolic unhealthy phenotypes in young and middle-aged obese patients and to assess their joint predictive ability. Patients and Methods: A cross-sectional study method was used to select 207 patients who were proposed to undergo weight loss surgery for morbid obesity from March to November 2022. Total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), liver fat content (LFC), cross-sectional area (CSAmuscle), and intermuscular adipose tissue (CSAIMAT) of paraspinal muscles were measured using quantitative computed tomography. Participants were categorized into two groups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The receiver operating characteristic curve comprised body composition variables that correlated with MUO, and the area under the curve (AUC) was calculated to compare their prediction capacity for MUO. Results: There were 71 patients with MHO (34.3%) and 136 patients with MUO (65.7%). The VAT, VAT/TAT ratio, LFC, and CSAmuscle was higher in MUO patients than in MHO (all P < 0.001), and SAT was lower than in MHO (P = 0.008). And all of these metrics were correlated with MUO (all P < 0.05). Inclusion of these body composition metrics in the ROC analysis showed that the AUC values for SAT, VAT, VAT/TAT ratio, LFC and CSAmuscle were 0.615, 0.663, 0.727, 0.694, 0.671, respectively, and the combination of the VAT/TAT ratio and the LFC had the ability to predict MUO best (AUC=0.746, P = 0.025). Conclusion: The combined use of VAT/TAT ratio and LFC is superior to the use of these two metrics alone in terms of their ability to predict the MUO, providing a more accurate approach to the management and prevention of obesity-related metabolic risk.

Resource-Efficient Direct Characterization of General Density Matrix.

Sequential weak measurements allow for the direct extraction of individual density-matrix elements, rather than relying on global reconstruction of the entire density matrix, which opens a new avenue for the characterization of quantum systems. Nevertheless, extending the sequential scheme to multiqudit quantum systems is challenging due to the requirement of multiple coupling processes for each qudit and the lack of appropriate precision evaluation. To address these issues, we propose a resource-efficient scheme (RES) that directly characterizes the density matrix of general multiqudit systems while optimizing measurements and establishing a feasible estimation analysis. In the RES, an efficient observable of the quantum system is constructed such that a single meter state coupled to each qudit is sufficient to extract the corresponding density-matrix element. An appropriate model based on the statistical distribution of errors is utilized to evaluate the precision and feasibility of the scheme. We have experimentally applied the RES to the direct characterization of general single-photon qutrit states and two-photon entangled states. The results show that the RES outperforms sequential schemes in terms of efficiency and precision in both weak- and strong-coupling scenarios. This Letter sheds new light on the practical characterization of large-scale quantum systems and the investigation of their nonclassical properties.

One-pot reaction for the preparation of diatom hemostatic particles with effective hemostasis and economic benefits.

Effective hemostatic materials have been in demand for rapid pre-hospital hemostasis in emergency situations, which can significantly reduce accidental deaths. The development of emergency hemostatic materials with rapid hemostasis, biosafety, and economical preparation is a great challenge. In this study, Ca(OH)2-complexed diatom powder hemostatic particles (Ca(OH)2-Php) were prepared based on a one-pot reaction by directly mixing various raw materials and by rotary granulation. High-temperature calcination was able to carbonate and consume the organic matter in the hemostatic particles. The crosslinked hydrogen bonds in those particles were converted to silica-oxygen bonds, the particles became more stable, and the porous structure of diatom biosilica (DBs) was exposed. Ca(OH)2-Php has high porosity, can quickly adsorb the water in blood (water absorption: 75.85 ± 6.93%), and exhibits rapid hemostasis capacity (clotting time was shortened by 43% compared with that of the control group), good biocompatibility (hemolysis rate <7%, no cytotoxicity), and simplicity of handling (conveniently debride, no residues, no tissue inflammation). This study provides a new idea for the preparation of emergency hemostatic materials, and Ca(OH)2-Php prepared by one-pot reaction has various high-quality characteristics including rapid hemostasis, wide applicability, economical preparation, and potential for large-scale production.

Worldwide trends in mortality for hypertensive heart disease from 1990 to 2019 with projection to 2034: data from the Global Burden of Disease 2019 study.

AIMS: This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths. METHODS AND RESULTS: Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts. CONCLUSION: The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.

This study provides the first comprehensive analysis of the age, period, and cohort trends in mortality for hypertensive heart disease (HHD) across 204 countries and territories from 1990 to 2019, with projection to 2034. The death burden of HHD is substantial and growing rapidly in most of the world, particularly in low- and middle-income countries (LMICs). Wide disparities exist within LMICs in HHD management, with most low socio-demographic index countries showing little progress in reducing HHD mortality. The examples from Brazil, China, and Ethiopia suggest that prevention policies for HHD can reduce risks for younger birth cohorts and shift the risks for all age groups over time.

Collateral vessels on preoperative enhanced computed tomography for predicting pathological grade of clear cell renal cell carcinoma: A retrospective study.

OBJECTIVES: To retrospectively evaluate the association between the presence of collateral vessels and grade of clear cell renal cell carcinoma (ccRCC) and whether the presence of collateral vessels could serve as a predictor to differentiate high- and low-grade ccRCC. MATERIALS AND METHODS: From May 2018 to September 2022, a total of 160 ccRCC patients with pathological diagnosis were enrolled in this study. Patients were divided into a high-grade group and a low-grade group according to World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system. The significant variables were extracted based on the univariate analyses using Student t test, Mann-Whitney U test, Chi-square test or Fisher's exact test. Multivariate logistic regression analyses were performed to determine independent factors among extracted variables. We calculated the sensitivity, specificity and their 95% confidence intervals (CI) of collateral vessels for predicting high WHO/ISUP grade to quantify its predictive performance. Furthermore, to investigate the additional predictive contribution of collateral vessels, a primary model and a control model were constructed to predict WHO/ISUP grade. The primary model included all extracted significant variables and the control model included significant variables except collateral vessels. RESULTS: The proportion of ccRCC patients with collateral vessels was significantly larger in high-grade ccRCC than those in low-grade ccRCC (87.5 % vs. 26.8 %, P < 0.001). Multivariate logistic regression analyses showed that the presence of collateral vessels was an independent predictor for high WHO/ISUP grade (P < 0.001). The sensitivity and specificity of the presence of collateral vessels for differentiating high- and low-grade ccRCC were 87.5 % (95 % CI 0.753-0.941) and 73.2 % (95 % CI 0.643-0.806) respectively. Including collateral vessels in predictive model improves predictive performance for WHO/ISUP grade, increasing the area under the curve (AUC) value from 0.889 to 0.914. CONCLUSION: The presence of collateral vessels has high sensitivity and specificity for differentiating high- and low-grade ccRCC and can improve the predictive performance for high WHO/ISUP grade.

Predictive models for starting dose of gonadotropin in controlled ovarian hyperstimulation: review and progress update.

Controlled ovarian hyperstimulation (COH) is an essential for in vitro fertilization-embryo transfer (IVF-ET) and an important aspect of assisted reproductive technology (ART). Individual starting doses of gonadotropin (Gn) is a critical decision in the process of COH. It has a crucial impact on the number of retrieved oocytes, the cancelling rate of ART cycles, and complications such as ovarian hyperstimulation syndrome (OHSS), as well as pregnancy outcomes. How to make clinical team more standardized and accurate in determining the starting dose of Gn is an important issue in reproductive medicine. In the past 20 years, research teams worldwide have explored prediction models for Gn starting doses. With the integration of artificial intelligence (AI) and deep learning, it is hoped that there will be more suitable predictive model for Gn starting dose in the future.

Negative serum (1,3) -ß-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR.

OBJECTIVE: The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results. METHODS: This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort. RESULTS: Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG. CONCLUSIONS: Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Study on the Biomolecular Competitive Mechanism of Polybrominated Diphenyl Ethers and Their Derivatives on Thyroid Hormones.

Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants. PBDEs and their derivatives, hydroxylated PBDEs (OH-PBDEs), can bind to hormone receptors and impact hormone secretion, transportation, and metabolism, leading to endocrine disruption and the development of various diseases. They have particularly strong interference effects on thyroid hormones. This study used decabromodiphenyl ether (BDE-209); 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); and 6-OH-BDE-47 as representative compounds of PBDEs and their derivatives, OH-PBDEs. A fluorescence probe, fluorescein-isothiocyanate-L-thyroxine (FITC-T4, F-T4), specific for binding to transthyretin (TTR), a thyroid transport protein, was prepared. The binding capacity of PBDEs and their derivatives, OH-PBDEs, to TTR was quantitatively measured using fluorescence spectroscopy. The principle of quenching the fluorescence intensity of F-T4 after binding to TTR was used to analyze the competitive interaction between the probe and BDE-209, BDE-47, and 6-OH-BDE-47, thereby evaluating the toxic effects of PBDEs and their derivatives on the thyroid system. Additionally, AutoDock molecular docking software (1.5.6) was used to further analyze the interference mechanism of OH-PBDEs on T4. The results of the study are as follows: (1) Different types of PBDEs and OH-PBDEs exhibit varying degrees of interference with T4. Both the degree of bromination and hydroxylation affect their ability to competitively bind to TTR. Higher bromination and hydroxylation degrees result in stronger competitive substitution. (2) The competitive substitution ability of the same disruptor varies at different concentrations. Higher concentrations lead to stronger substitution ability, but there is a threshold beyond which the substitution ability no longer increases. (3) When OH-PBDEs have four or more bromine atoms and exhibit the most structural similarity to T4, their binding affinity to TTR is stronger than that of T4.

Changes in Bone Mineral Density and Related Influencing Factors Assessed by Quantitative Computed Tomography in Maintenance Dialysis Patients.

OBJECTIVE: To investigate the changes in volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT) in chronic kidney disease (CKD) patients on maintenance dialysis. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China, from March to July 2022. METHODOLOGY: Maintenance dialysis patients were selected for this study, and parameters related to renal function and bone metabolism markers were recorded. Patients undergoing routine physical examination were age-matched with maintenance dialysis patients to serve as the control group. vBMD scans of the lumbar spine (L1-3) were obtained by QCT for all participants. RESULTS: Among the 141 maintenance dialysis patients, there were 67 patients with secondary hyperparathyroidism (SHPT) and 74 patients with non-secondary hyperparathyroidism (non-SHPT) with mean vBMDs of 145.99±55.13 mg/cm3 and 129.10±44.20 mg/cm3, respectively. The 159 individuals in the control group had mean age of 52.77±11.66 years and mean vBMD of 129.62±36.36 mg/cm3. The vBMD of the SHPT group was greater than that of both the non-SHPT group and the control group (all p<0.05). For dialysis patients, vBMD was positively correlated with calcium-phosphorus product and intact parathyroid hormone (iPTH) levels (r = 0.181, 0.214, respectively, p<0.05); vBMD was inversely correlated with age (r = -0.555, p<0.05). After adjusting for the covariates, vBMD remained positively correlated with iPTH (r = 0.184, p<0.05). CONCLUSION: Increased lumbar vertebral vBMD in maintenance dialysis patients may be associated with high iPTH, providing clinicians with a new understanding of the changes in bone mineral density in maintenance dialysis patients. KEY WORDS: Bone mineral density, Quantitative computed tomography, Chronic kidney disease, Maintenance dialysis.

Research on classification method of high myopic maculopathy based on retinal fundus images and optimized ALFA-Mix active learning algorithm.

AIM: To conduct a classification study of high myopic maculopathy (HMM) using limited datasets, including tessellated fundus, diffuse chorioretinal atrophy, patchy chorioretinal atrophy, and macular atrophy, and minimize annotation costs, and to optimize the ALFA-Mix active learning algorithm and apply it to HMM classification. METHODS: The optimized ALFA-Mix algorithm (ALFA-Mix+) was compared with five algorithms, including ALFA-Mix. Four models, including ResNet18, were established. Each algorithm was combined with four models for experiments on the HMM dataset. Each experiment consisted of 20 active learning rounds, with 100 images selected per round. The algorithm was evaluated by comparing the number of rounds in which ALFA-Mix+ outperformed other algorithms. Finally, this study employed six models, including EfficientFormer, to classify HMM. The best-performing model among these models was selected as the baseline model and combined with the ALFA-Mix+ algorithm to achieve satisfactory classification results with a small dataset. RESULTS: ALFA-Mix+ outperforms other algorithms with an average superiority of 16.6, 14.75, 16.8, and 16.7 rounds in terms of accuracy, sensitivity, specificity, and Kappa value, respectively. This study conducted experiments on classifying HMM using several advanced deep learning models with a complete training set of 4252 images. The EfficientFormer achieved the best results with an accuracy, sensitivity, specificity, and Kappa value of 0.8821, 0.8334, 0.9693, and 0.8339, respectively. Therefore, by combining ALFA-Mix+ with EfficientFormer, this study achieved results with an accuracy, sensitivity, specificity, and Kappa value of 0.8964, 0.8643, 0.9721, and 0.8537, respectively. CONCLUSION: The ALFA-Mix+ algorithm reduces the required samples without compromising accuracy. Compared to other algorithms, ALFA-Mix+ outperforms in more rounds of experiments. It effectively selects valuable samples compared to other algorithms. In HMM classification, combining ALFA-Mix+ with EfficientFormer enhances model performance, further demonstrating the effectiveness of ALFA-Mix+.

Targeting PTGES/PGE2 axis enhances sensitivity of colorectal cancer cells to 5-fluorouracil.

Insensitivity and resistance to 5-fluorouracil (5FU) remain as major hurdles for effective and durable 5FU-based chemotherapy in colorectal cancer (CRC) patients. In this study, we identified prostaglandin E synthase (PTGES)/prostaglandin E2 (PGE2) axis as an important regulator for 5FU sensitivity in CRC cells. We found that PTGES expression and PGE2 production are elevated in CRC cells in comparison to normal colorectal epithelial cells. Depletion of PTGES significantly enhanced the inhibitory effect of 5FU on CRC cell viability that was fully reverted by exogenous supplement of PGE2. Inhibition of PTGES enzymatic function, by either inducing loss-of-function mutant or treatment with selective inhibitors, phenocopied the PTGES depletion in terms of 5FU sensitization. Mechanistically, PTGES/PGE2 axis modulates glycolysis in CRC cells, thereby regulating the 5FU sensitivity. Importantly, high PTGES expression is correlated with poor prognosis in 5FU-treated CRC patients. Thus, our study defines PTGES/PGE2 axis as a novel therapeutic target for enhancing the efficacy of 5FU-based chemotherapy in CRC.

Genome-Wide Identification and Expression Analysis of the bHLH Transcription Factor Family and Its Response to Abiotic Stress in Mongolian Oak (Quercus mongolica).

The basic helix-loop-helix (bHLH) family, one of the largest families of transcription factors in plants, is extensively involved in the growth, development, and stress response of several woody plants. However, no systematic analysis of the bHLH gene family in Quercus mongolica has been reported. We characterize QmbHLH genes and identify the functions of QmbHLH proteins in Q. mongolica. We used bioinformatics approaches, qRT-PCR analysis, and RNA sequencing data to examine chromosomal distributions, gene structures, and conserved patterns, and identified 89 QmbHLH genes, which were divided into 21 subgroups based on the phylogenetic analysis of bHLH genes in Arabidopsis thaliana. Segmental replication played a more prominent role than tandem duplication in the expansion of the QmbHLH gene family. Based on patterns of tissue-specific expression, protein interactions, and cis-element analysis, QmbHLH genes may be extensively involved in the growth and development of Q. mongolica. In leaves, stems, and roots, 12 selected QmbHLH genes exhibited responsiveness to abiotic stresses (salt, cold, weak light, and drought). Our study facilitates follow-up functional investigations of the bHLH gene family in Q. mongolica and provides novel insights into bHLH superfamilies in woody plants.