Novel Genetic Loci in Early-Onset Gout Derived From Whole-Genome Sequencing of an Adolescent Gout Cohort.

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset ≤30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

Comparison of Structural and Physicochemical Characteristics of Skin Collagen from Chum Salmon (Cold-Water Fish) and Nile Tilapia (Warm-Water Fish).

This study compared collagens from cold-water and warm-water fish for their structural, rheological, and functional properties, and explored their potential applications, aiming to realize the high-value utilization of marine biological resources. To this end, chum salmon skin collagen (CSSC) and Nile tilapia skin collagen (NTSC) were both successfully extracted. Collagens from the two species had different primary and secondary structures, with NTSC having a higher molecular weight, imino acid content, and α-helices and ß-turns content. The denaturation temperatures were 12.01 °C for CSSC and 31.31 °C for NTSC. CSSC was dominated by viscous behavior and its structure varied with temperature, while NTSC was dominated by elastic behavior and its structure remained stable with temperature. Both collagens had good oil holding capacity, foaming capacity, and emulsifying activity, but NTSC had better water holding capacity and foaming and emulsifying stability. Their different properties make CSSC more suitable for the preservation of frozen and chilled foods and the production of sparkling beverages, and give NTSC greater potential in biofunctional materials and solid food processing.

SNSynergy: Similarity network-based machine learning framework for synergy prediction towards new cell lines and new anticancer drug combinations.

The computational method has been proven to be a promising means for pre-screening large-scale anticancer drug combinations to support precision oncology applications. Pioneering efforts have been made to develop machine learning technology for predicting drug synergy, but high computational cost for training models as well as great diversity and limited size in screening data escalate the difficulty of prediction. To address this challenge, we propose a simple machine learning framework, namely Similarity Network-based Synergy prediction (SNSynergy), for predicting synergistic effects towards new cell lines and new drug combinations by two locally weighted models CLSN and DCSN. This framework only requires a small amount of auxiliary data, like genomics information of cell lines and the molecular fingerprints or targets of drugs. Based on the assumption that similar cell lines and similar drug combinations have similar synergistic effects, CLSN and DCSN predict synergy scores through capturing individual synergy contributions of nearest cell line and drug combination neighbors, respectively. High correlations between predicted and measured synergy scores on two leading cancer cell line pharmacogenomic screening datasets (the O'Neil dataset and the NCI-ALMANAC dataset) demonstrate the effectiveness and robustness of SNSynergy. Many of the identified drug combinations are consistent with previous studies, or have been explored in clinical settings against the specific cancer type, showing that SNSynergy has the potential to supply cost-saving and effective high-throughput screening for prioritizing the most applicable cell lines and the most promising drug combinations.

Fabrication and characterisation of collagen/pullulan ultra-thin fibers by electrospinning.

Collagen electrospun fibers are promising materials for food packaging and tissue engineering. The conventional electrospinning of collagen, however, is usually carried out by dissolving it in organic reagents, which are toxic. In this study, collagen/pullulan (COL/PUL) ultra-thin fibers were prepared by electrospinning using acetic acid as a solvent. Compared to the conventional preparation method, the proposed method is safe and does not produce toxic solvent residues. The introduction of PUL increased the degree of molecular entanglement in the solution, so the viscosity of the COL/PUL electrospun solution increased from 0.50 ± 0.01 Pa∙s to 4.40 ± 0.08 Pa∙s, and the electrical conductivity decreased from 1954.00 ± 1.00 mS/cm to 1372.33 ± 0.58 mS/cm. Scanning electron microscopy analysis confirmed that PUL improved the spinnability of COL, and smooth, defect-free COL/PUL ultra-thin fibers with diameters of 215.32 ± 40.56 nm and 240.97 ± 53.93 nm were successfully prepared at a viscosity of greater than 1.18 Pa∙s. As the proportion of PUL increased, intramolecular hydrogen bonds became the dominant interaction between COL and PUL. The intermolecular hydrogen bonding content decreased from 52.05 % to 36.45 %, and the intramolecular hydrogen bonding content increased from 46.11 % to 62.95 %. The COL was gradually unfolded, the content of α-helices decreased from 33.57 % to 25.91 % and the random coils increased from 34.22 % to 40.09 %. More than 36 % of the triple helix fraction of COL was retained by the COL/PUL ultra-thin fibers, whereas only 16 % of the triple helix fraction of COL was retained by the COL nanofibers prepared with 2.2.2-trifluoroethanol. These results could serve as a reference for the development of green food COL-based fibers.

Clinical characteristics of adolescent-onset gout in Chinese: A hospital-based cross-sectional study.

OBJECTIVE: Adolescent-onset gout has a greater impact on the lives and health of patients than adult-onset gout. However, there is a relative lack of clinical information on adolescent-onset gout. Hence, we analyzed a Chinese cohort. METHODS: We studied clinical features of 9,003 Chinese patients. Gout onset age of 12 - 19 years is defined as adolescent-onset group (AG), 20 - 40 years as early-onset group (EG), and 41 - 64 years as late-onset group (LG). Multivariable regression analysis evaluated factors associated with recurrent flares, serum urate (SU) levels, and underexcretion type in AG. RESULTS: Compared with EG and LG, the AG had higher SU levels [AG: 9.5 (2.2) mg/dL, EG: 8.6 (2.1) mg/dL, LG: 7.73 (2.0) mg/dL, P < 0.001], higher percentage of positive family history of gout (AG: 41.8 %, EG: 29.6 %, LG: 24.6 %, P < 0.001), underexcretion type (AG: 62.4 %, EG: 62.5 %, LG: 58.8 %, P = 0.04), recurrent flares (AG: 78.1 %, EG: 70.3 %, LG: 68.9 %, P = 0.01). Urate-lowering therapy (ULT) initiated [OR 6.58 (95 % CI 1.35 - 32.00)] and hypercholesterolemia [OR 4.16 (95 % CI 1.28 - 13.53)] were associated with recurrent flares. eGFR was identified to be a significant variable of increasing SU levels [beta -0.24 (95 % CI -0.04 to -0.01)]. Hypertriglyceridemia [OR 0.35 (95 % CI 0.17 - 0.71)] was related to underexcretion type. CONCLUSION: Adolescent-onset gout patients had clinically distinctive features with higher SU levels, BMI, positive gout family history, underexcretion type and recurrent flares. These specific populations were less likely to achieve ULT target, requiring more clinical attention.

Vertical Distribution Mapping for Methane Fugitive Emissions Using Laser Path-Integral Sensing in Non-Cooperative Open Paths.

Observing the vertical diffusion distribution of methane fugitive emissions from oil/gas facilities is significant for predicting the pollutant's spatiotemporal transport and quantifying the random emission sources. A method is proposed for methane's vertical distribution mapping by combining the laser path-integral sensing in non-non-cooperative open paths and the computer-assisted tomography (CAT) techniques. It uses a vertical-plume-mapping optical path configuration and adapts the developed dynamic relaxation and simultaneous algebraic reconstruction technique (DR-SART) into methane-emission-distribution reconstruction. A self-made miniaturized TDLAS telemetry sensor provides a reliable path to integral concentration information in non-non-cooperative open paths, with Allan variance analysis yielding a 3.59 ppm·m sensitivity. We employed a six-indexes system for the reconstruction performance analysis of four potential optical path-projection configurations and conducted the corresponding validation experiment. The results have shown that that of multiple fan-beams combined with parallel-beam modes (MFPM) is better than the other optical path-projection configurations, and its reconstruction similarity coefficient (ε) is at least 22.4% higher. For the different methane gas bag-layout schemes, the reconstruction errors of maximum concentration (γm) are consistently around 0.05, with the positional errors of maximum concentration (δ) falling within the range of 0.01 to 0.025. Moreover, considering the trade-off between scanning duration and reconstruction accuracy, it is recommended to appropriately extend the sensor measurement time on a single optical path to mitigate the impact of mechanical vibrations induced by scanning motion.

Effect of pH on the Structure, Functional Properties and Rheological Properties of Collagen from Greenfin Horse-Faced Filefish (Thamnaconus septentrionalis) Skin.

Collagen is an important biopolymer widely used in food, cosmetics and biomedical applications. Understanding the effect of pH on the structure and properties of collagen is beneficial for its further processing and exploitation. In this study, greenfin horse-faced filefish skin collagen (GHSC) was prepared and identified as a type I collagen. We systematically investigated the effect of pH on the structural, functional and rheological properties of GHSC. Scanning electron microscopy showed that the collagen morphology changed from an ordered stacked sheet structure to a rough silk-like structure as pH increased. Gaussian-fitted Fourier infrared spectroscopy results of the collagen revealed that it unfolded with increasing pH. Moreover, the ordered structure was reduced, and random coils became the dominant conformation. Its ß-sheet and random coil contents increased from 18.43 ± 0.08 and 33.62 ± 0.17 to 19.72 ± 0.02 and 39.53 ± 1.03%, respectively, with increasing pH. α-helices and ß-turns decreased from 35.00 ± 0.26 and 12.95 ± 0.01 to 29.39 ± 0.92 and 11.36 ± 0.10%, respectively. The increase in ß-sheets and random coils allowed the pI-treated collagen to exhibit maximum water contact angle. The emulsification and foaming properties decreased and then increased with increasing pH in a V-shape. The increased net surface charge and ß-sheets in collagen benefited its emulsification and foaming properties. The rheological results showed that the protoprotein exhibited shear-thinning properties in all pH ranges. The collagen solutions showed liquid-like behaviour in low-pH (2, 4) solutions and solid-like behaviour in high-pH (6, 7.83 and 10) solutions. Moreover, the frequency-dependent properties of the storage modulus (G') and loss modulus (G″) of the collagen solutions weakened with increasing pH. Collagen has considerable frequency-dependent properties of G' and G″ at low pH (2, 4). Thus, the importance of collagen raw material preparation for subsequent processing was emphasised, which may provide new insights into applying collagen-based materials in food, biomaterials and tissue engineering.

Assessing the policy benefits of constructing "Zero-waste Cities" in China: From the perspective of hazardous waste lifecycle management.

Based on China's quasi-natural experiment of constructing "Zero-waste Cities", this study assessed its policy benefits on hazardous waste lifecycle management. Utilizing the theory of difference-in-differences analysis, the study quantifies the net benefits of the policy in 10 pilot cities using an average treatment effect formula, and the results indicate a reduction of 162,900 tons/year in waste generation, an increase of 2.3 % in utilization and disposal rate, and a decrease of 28,200 tons/year in end-of-pipe storage. By constructing a regression model and employing robustness tests such as changing control variables, substituting the explained variable, re-matching control groups, and random assignment of pilot sites, the study confirms that the significant policy benefits primarily lie in source reduction, with a reduction intensity of approximately 1.73 tons/100 million yuan of industrial GDP. Additionally, by applying the mixed-effects model and mediation-analysis model, the study finds that the policy benefit of source reduction exhibits a lag effect, and during the pilot period, the main approach to achieving the benefit was through enhancing cleaner production in companies rather than adjusting industrial structures in cites.

Source apportionment and risk assessment of heavy metals in typical greenhouse vegetable soils in Shenyang, China.

In this study, the concentrations of Cr, Cu, Ni, Pb, Zn, Cd, As, and Hg in the typical greenhouse vegetable soils in Shenyang, Northeast of China, were determined, and the pollution characteristics and primary sources of heavy mental pollution in soil were analyzed. Results showed that the sum of the mean values of eight typical heavy metals in the soil of the greenhouse soils was 219.79 mg/kg. According to the "Chinese Environmental Quality Evaluation Standard for Farmland of Greenhouse Vegetables Production" (HJ/T 333-2006), the concentrations of Cu (33.50 ± 11.99 mg/kg), Cd (0.246 ± 0.156 mg/kg), and Hg (0.214 ± 0.177 mg/kg) exceeded the limit values in 14.29%, 39.29%, and 39.29% of sampling points, respectively. The single factor pollution index and the Nemerow comprehensive pollution index of heavy metal elements showed that most greenhouse soils were at safety, alert, or light pollution levels. The potential ecological risk index (RI = 505.19) showed that 42.86% of the samples were at high or very high risk and Cd and Hg were the main ecological risk factors. Based on the result of correlation analysis, the Positive Matrix Factorization (PMF) differentiated sources of heavy metal pollution in the study area into four components, including fertilizer input, soil parent material, pesticide spraying and raw coal combustion, and plastic film mulching, which accounted for 36.76%, 22.64%, 20.89%, and 19.71%, respectively, of the total sources of heavy metals.

Identification of ground spilled oil of buried pipeline based on laser absorption spectroscopy: Numerical investigation and experimental verification.

The ground diffusion characteristics of buried oil pipeline after leakage and the laser optical transmission mechanism of surface oil film are the basis of spectral detection technology. Based on the computational fluid dynamics to solve the diffusion equation of multiphase flow in porous media, the leakage law of oil under different soil porosity is analyzed in two dimensions: surface diffusion diameter and oil film thickness. TracePro optical simulation is used to study the absorption and reflection patterns of laser at the oil-gas interface, and validation experiments are carried out based on the tunable diode laser absorption spectroscopy method. The results show that oil is easily accumulated on the ground surface with larger soil porosity and in the depressions of the ground surface. When the oil film thickness is greater than 2 mm, the laser cannot transmit the oil layer and the received light intensity is only provided by the mirror reflection at the oil-gas interface. The mechanism of laser detection of oil leaks is the spectral absorption of volatile alkane gases in the upper layer of the oil film by a laser of a specific wavelength.

Reduced myocardial strain of interventricular septum among male amateur marathon runners: a cardiac magnetic resonance study.

OBJECTIVES: To analyze the long-term effect of multiple marathons on cardiac structure and function in amateur marathon runners compared with healthy controls. DESIGN: Cross-sectional study using male amateur marathon runners (n = 32) and age-matched cohort of male healthy controls (n = 12). METHODS: A total of 32 male amateur marathon runners (age 44 ±â€¯7 years) and 12 male healthy controls (age 42 ±â€¯8 years) underwent cardiac magnetic resonance (CMR). The relevant parameters of cardiac structure and function were studied employing feature-tracking strain analysis. RESULTS: Amateur marathon runners showed lower heart rates, body mass index and body surface area. The left ventricular (LV) mass index, LV end-diastolic volume index and right ventricular end-systolic volume index were significantly higher in amateur marathon runners compared with healthy controls. Furthermore, walls of interventricular septum (IVS) in amateur marathon runners were thicker than healthy controls. There was no significant difference between two groups in the global myocardial strain (MS) in LV. However, the segmental radial and circumferential strains of the LV were lower in amateur marathon runners compared to healthy controls, specifically in the 8th and 9th segments. Finally, we also found as the total running intensity increased, so did global longitudinal strain. CONCLUSIONS: We reported higher wall thickness and lower regional radial and circumferential strain in the IVS region in amateur marathon runners, suggesting that prolonged and high-intensity exercise may cause cardiac remodeling. Further studies are needed to investigate whether this is an adaptive or maladaptive change in amateur marathon runners.

Suppression of P2X7R by Local Treatment Alleviates Acute Gouty Inflammation.

Objective: Gout is the most common inflammatory arthritis associated with interleukin-1ß (IL-1ß) accumulation during exacerbation. In this study, we aimed to clarify whether potassium channel antagonists attenuate local inflammation in mice with monosodium urate (MSU)-induced gout. Methods: We cultured human macrophage THP-1 cells and evaluated the molecular levels of both IL-1ß and potassium channels stimulated with MSU and/or potassium channel antagonists. Acute gout models were generated in IL-1ß luciferase transgenic male mice using synovium-like subcutaneous air pouches with MSU injection. Their luciferase activities were monitored following potassium channel blocker treatment using the IVIS Spectrum CT imaging system. The lavages and tissues were extracted from their air pouches, followed by cell counting and pathological analysis. Results: MSU stimulation increased the gene expression levels of pro-IL-1ß, P2x7r and Kv1.3, whereas the expression of Kcnq1 was decreased in phorbol 12-myristate 13-acetate-induced THP-1 cells. Both high and low concentrations of the P2x7 receptor inhibitor adenosine 5'-triphosphate (ATP) derivative periodate oxidized ATP (oATP) decreased the production of IL-1ß in the supernatant of THP-1 cells. The sixth hour was the peak time of IL-1ß luciferase activity after MSU intervention in vivo. oATP ameliorated the synovial IL-1ß luciferase activity, reduced inflammatory cell infiltration and alleviated the erosive damage in the cartilage. Conclusion: The anti-inflammatory properties of potassium channel inhibitors, especially of oATP, might point to new strategies for local anti-inflammatory therapy for acute gout.

Forward osmosis membrane doped with water-based zirconium fumarate MOFs to enhance dye pollutant removal and membrane antifouling performance.

Metal-organic frameworks (MOFs) can be applied to enhance the property of forward osmosis membranes. However, organic solvents can easily remain in organic synthetic metal-organic frame materials and cause membrane fouling and a decrease in membrane permeability. In this study, water-based Zr-fumarate MOFs were synthesized and doped into the membrane active layer by interfacial polymerization to provide a water-based MOF-doped thin-film composite membrane (TFC membrane). It was found that doping the water-based MOFs effectively improved membrane hydrophilicity, and nanowater passages were introduced in the active layer to improve permeability. The water flux of the water-based MOF-doped TFC membranes was increased by 21% over that of the original membrane, and the selectivity performance of the membrane was improved while keeping the salt rejection basically unchanged. Additionally, the water-based MOF-doped TFC membrane showed good removal efficiency (Rd > 94%) and strong antipollution performance in the treatment of dye pollutants.

Changes of serum uric acid level during acute gout flare and related factors.

Objective: By studying the changes of serum uric acid (SUA) in acute stage and remission stage of gouty arthritis, we aimed to explore the relationship between the changes of SUA level and free glucocorticoids and inflammatory factors. Methods: A prospective, longitudinal study was conducted on 50 acute gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. Blood and 24-hour urine samples were collected during the acute phase and two weeks after the initial visit. Patients with acute gouty arthritis were treated primarily with colchicine and nonsteroidal anti-inflammatory drugs. Results: A total of 32 patients completed the two-week follow-up trial. SUA levels were significantly downregulated during the acute flare than after the flare (464.14 ± 90.97 vs. 527.36 ± 86.90 µmol/L, p < 0.001). The 24-hour fractional excretion of uric acid (24 h FEur) (5.54 ± 2.82% vs. 4.68 ± 2.83%, p < 0.001) and 24-hour urinary uric acid excretion (24 h Uur) (663.08 ± 249.48 µmol/L vs. 540.87 ± 263.18 µmol/L, p = 0.001) increased significantly in patients during the acute phase. The percent change in SUA was associated with those in 24 h FEur and C-reactive protein. Meanwhile, the percent change in 24 h Uur was associated with those in 24-hour urinary free cortisol, percent change in interleukin 1ß and interleukin 6. Conclusion: Decreased SUA level during the acute gout flare was associated with increased excretion of urinary uric acid. Inflammatory factors and bioactive free glucocorticoids may play significant roles in this process.

Hippocampal Subfield Volumes in Amateur Marathon Runners.

PURPOSE: Numerous studies have implicated the involvement of structure and function of the hippocampus in physical exercise, and the larger hippocampal volume is one of the relevant benefits reported in exercise. It remains to be determined how the different subfields of hippocampus respond to physical exercise. METHODS: A 3D T1-weighted magnetic resonance imaging was acquired in 73 amateur marathon runners (AMR) and 52 healthy controls (HC) matched with age, sex, and education. The Montreal Cognitive Assessment, the Pittsburgh Sleep Quality Index (PSQI), and the Fatigue Severity Scale were assessed in all participants. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the two groups and ascertained correlation between the significant subfield metrics and the significant behavioral measure in AMR group. RESULTS: The AMR had significantly better sleep than HC, manifested as with lower score of PSQI. Sleep duration in AMR and HC was not significantly different from each other. In the AMR group, the left and right hippocampus, cornu ammonis 1 (CA1), CA4, granule cell and molecular layers of the dentate gyrus, molecular layer, left CA2-3, and left hippocampal-amygdaloid transition area volumes were significantly larger compared with those in the HC group. In AMR group, the correlations between the PSQI and the hippocampal subfield volumes were not significant. No correlations were found between hippocampal subfield volumes and sleep duration in AMR group. CONCLUSIONS: We reported larger volumes of specific hippocampal subfields in AMR, which may provide a hippocampal volumetric reserve that protects against age-related hippocampal deterioration. These findings should be further investigated in longitudinal studies.

Prediction of wavefront distortion for wavefront sensorless adaptive optics based on deep learning.

Aimed at the slow detection speed and low measurement accuracy of wavefront aberration in current wavefront sensorless adaptive optic technology, different convolution neural networks (CNNs) are established to detect the turbulence wavefront, including an ordinary convolutional neural network, a ResNet network, and an EfficientNet-B0 network. By using the nonlinear fitting ability of deep neural networks, the mapping relationship between Zernike coefficients and focal degraded image can be established. The simulation results show that the optimal network model after training can quickly and efficiently predict the Zernike coefficients directly from a single focal degraded image. The root-mean-square errors of the wavefront detection accuracy of the three networks are 0.075λ, 0.058λ, and 0.013λ, and the time consumed for predicting the wavefront from the single degraded image are 2.3, 4.6, and 3.4 ms, respectively. Among the three networks presented, the EfficientNet-B0 CNN has obvious advantages in wavefront detection accuracy and speed under different turbulence intensities than the ordinary CNN and ResNet networks. Compared with the traditional method, the deep learning method has the advantages of high precision and fast speed, without iteration and the local minimum problem, when solving wavefront aberration.

Valorization of Fish Processing By-Products: Microstructural, Rheological, Functional, and Properties of Silver Carp Skin Type I Collagen.

The objective of this study was to develop aquatic collagen production from fish processing by-product skin as a possible alternative to terrestrial sources. Silver carp skin collagen (SCSC) was isolated and identified as type I collagen, and LC-MS/MS analysis confirmed the SCSC as Hypophthalmichthys molitrix type I collagen, where the yield of SCSC was 40.35 ± 0.63% (dry basis weight). The thermal denaturation temperature (Td) value of SCSC was 30.37 °C, which was superior to the collagen of deep-sea fish and freshwater fish. Notably, SCSC had higher thermal stability than human placental collagen, and the rheological experiments showed that the SCSC was a shear-thinning pseudoplastic fluid. Moreover, SCSC was functionally superior to some other collagens from terrestrial sources, such as sheep, chicken cartilage, and pig skin collagen. Additionally, SCSC could provide a suitable environment for MC3T3-E1 cell growth and maintain normal cellular morphology. These results indicated that SCSC could be used for further applications in food, cosmetics, and biomedical fields.

Palpable tophi and more comorbidities associated with adherence to urate-lowering medical therapy in a Chinese gout cohort.

OBJECTIVE: Urate-lowering therapy (ULT) nonadherence is common and problematic in gout. Since, sociocultural factors affect adherence, we analyzed a Chinese cohort. METHODS: We studied 903 Chinese gout patients aged 46.4±14.7 years (mean±SD), uniquely extending to assay of 2-year medication possession ratio (MPR) ≥80% defined as high adherence. Multivariable logistic regression analyses evaluated factors linked with adherence and ULT target attainment. RESULTS: Characterization of ULT outcomes in this cohort revealed that after 2 years ULT, MPR ≥80% patients had better target serum urate (SU) achievement (from 23.3% to 71.0%, P <0.001), lower flare frequency and palpable tophi compared to MPR <80%. However, only 44.7% of cohort subjects had MPR ≥80%. Male sex (OR 3.68), gout onset age >60 years (OR 3.51), disease duration >5 years (OR 1.70), more comorbidities (OR 1.74), baseline palpable tophi (OR 1.53), SU <6mg/dL (360µmol/L) (OR 1.92) and more frequent follow-up visits (OR 1.98) were significantly associated with high adherence. Nevertheless, significant independent risk factors for failed SU target achievement included male sex (OR 0.36) and more comorbidities (OR 0.85). CONCLUSION: Despite adherence to ULT linked to better outcomes for flares and tophi, the more adherent Chinese male patients and those with more comorbidities had decreased target SU attainment. Differences in adherence of Chinese gout patients compared to several primarily Western studies emphasize the importance of not stereotyping gout patients for projected nonadherence. Results underline the dual importance of identifying gout patients more likely to be ULT-adherent and leveraging adherence to drive treatment to SU target.

Predicting breast cancer recurrence and metastasis risk by integrating color and texture features of histopathological images and machine learning technologies.

About 30%-40% breast cancer patients suffer from recurrence and metastasis, even after targeted therapy like trastuzumab. Since breast cancer recurrence and metastasis are intrinsically related to mortality, it is critical to predict the recurrence and metastasis risk of an individual patient, which is essential for adjuvant therapy and early intervention. In this study, we developed a novel breast cancer recurrence and metastasis risk assessment framework from histopathological images using image features and machine learning technologies. The detection framework was applied on a manually collected clinical dataset from the Cancer Hospital, Chinese Academy of Medical Sciences, consisting of 127 breast cancer patients with known prognostic information; and further independently validated on 88 formalin-fixed, paraffin-embedded (FFPE) samples downloaded from The Cancer Genome Atlas (TCGA) with known recurrence and metastasis status. As a result, the XGBoost-based method performed well using only 8 texture and color features, obtained internal testing AUC of 0.75 on clinical data and external testing AUC of 0.72 on TCGA FFPE data, respectively. In addition, this study found two important potential predictors, i.e., the second moment of the B color component and the detail level mean square error of the wavelet multi-sub-bands co-occurrence matrix. Our study benchmarked the performances of histopathological image features and machine learning technologies in the recurrence and metastasis risk assessment, and holds promise for relieving pathologists' workload and boosting the survival chances of the breast cancer patients.

Physical optimization of cell proliferation and differentiation using spinner flask and microcarriers.

The traditional breeding industry has been increasingly saturated and caused environmental pollution, disease transmission, excessive resource use, and methane emission; however, it still cannot meet the needs of the growing population. To explore other alternatives, researchers focused on cell agriculture and cell-based meat, especially large-scale cell culture. As a prerequisite for production, large-scale culture technology has become an important bottleneck restricting cell-based meat industrialization. In this study, the single-factor variable method was adopted to examine the influence of Cytodex1 microcarrier pretreatment, spinner flask reaction vessel, cell culture medium, serum and cell incubation, and other influencing factors on large-scale cell cultures to identify the optimization parameters suitable for 3D culture environment. Collagen and 3D culture were also prospectively explored to promote myogenesis and cultivate tissue-like muscle fibers that contract spontaneously. This research lays a theoretical foundation and an exploratory practice for large-scale cell cultures and provides a study reference for the microenvironment of myoblast culture in vitro, a feasible direction for the cell therapy of muscular dystrophy, and prerequisites for the industrialized manufacturing of cell-based meat. Graphical summary: Research on large-scale myoblast culture using spinner flasks and microcarriers. For cell culture, the microcarriers were pretreated with UV and collagen. Cell seeding condition, spinner flask speed, resting time, and spinner flask culture microenvironment were then optimized. Finally, two culture systems were prepared: a culture system based on large-scale cell expansion and a culture system for myogenesis promotion and differentiation.