[Consumption status and growth trends of dairy products among children and adolescents in China from 1991 to 2018].

OBJECTIVE: To explore the dairy consumption among children and adolescents aged 7-17 in China. METHODS: 10 rounds of follow-up data from the "China Health and Nutrition Survey" from 1991 to 2018 were collected, and individuals aged 7-17 were selected as the study subjects. Dietary data was collected by using 3-day 24-hour dietary review method and household weighing accounting method(edible oils and seasonings). Dairy consumption was calculated by converting various dairy products into liquid milk intake using the China Food Composition. After excluding those with missing demographic information, missing data from the "3 days and 24 hours" dietary survey, and abnormal daily energy intake, 18 529 participants were included in the final analysis. Joinpoint regression model was used to analyze the trend of changes in dairy intake. RESULTS: The dairy consumption rate increased from 2.8% in 1991 to 42.3% in 2018, while it increased from 8.4% to 58.8% in urban and from 0.9% to 32.1% in rural areas. Meanwhile, the proportion of people whose dairy intake reaches the recommended intake(300 g/d) increased from 0.2% to 3.0%, and the proportion in rural area was 2.0%, which was lower than that in urban areas(4.9%). From 1991 to 2018, dairy intake increased at a rate of 12.97%(P=0.02), and the growth rate of urban and rural areas were 9.79%(P=0.03) and 15.67%(P<0.01), respectively. There was a faster growth trend from 1991-2004 compared to 2004-2018. The growth rate in urban and rural areas also showed different growth trends. CONCLUSION: The dairy intake of children and adolescents aged 7-17 in China improved significantly from 1991 to 2018, with higher consumption rate in urban areas than in rural areas, but it still need to be improved for health.

[Analysis of food carbon footprint and its socio-demographic disparities in China in 2018].

OBJECTIVE: To analyze food carbon footprint and its socio-demographic disparities among adults in China. METHODS: A total of 12 777 adults aged 18 years and above from the China Health and Nutrition Survey in 2018 who have completed dietary and socio-demographic data were analyzed. The information of food intake were collected by 24 h recalls combined with the weighing of household seasonings. Food consumption was converted into energy intake by the China Food Composition Table. Carbon footprint of 26 food groups were calculated by the food carbon footprint database based on life-cycle assessment(LCA), multinomial logit model was used to analyze the association of socio-demographic factors and food carbon footprint. RESULTS: Average food carbon footprint were decreased with increasing age while increased with increasing income and education levels, and was higher among male than that among female, was higher among urban residents than that among rural residents, was higher in the south than that in the north. Multinomial logit analysis showed that compared with people aged 18-44, the likelihood of occurring high carbon footprint in 60y and above group were 29%(OR=0.71, 95%CI 0.61-0.83) lower than that occurring low carbon footprint. Women were 11%(OR=0.89, 95%CI 0.81-0.99) and 25%(OR=0.75, 95%CI 0.67-0.84) less likely to appear medium and high carbon footprint than low carbon footprint, compared with their male counterparts. In comparison to people living in cities, rural dwellers were 24%(OR=0.76, 95%CI 0.69-0.85) and 38%(OR=0.62, 95%CI 0.55-0.70) less likely to appear medium and high carbon footprint than low carbon footprint. People in the south were 3.89 times(95%CI 3.52-4.30) and 11.35 times(95%CI 10.01-12.88) more likely to occur medium and high carbon footprint than low carbon footprint, compared with people in the north. Participants were more likely to occur medium carbon footprint and high carbon footprint with the increasing income level(OR>1), and were more likely to occur high carbon footprint with the increasing education level(OR>1). CONCLUSION: The food carbon footprint of adults in China in 2018 show different socio-demographic disparities, gender, income and education level are significant factors.

[Change of dietary pattern among young people aged 18-35 in China from 1989 to 2018].

OBJECTIVE: To analyze the dietary patterns changes of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) from 1989 to 2018. METHODS: Using the data of China Health and Nutrition Survey, a total of 25 400 young people aged 18-35 with complete dietary and sociodemographic information from 1989 to 2018 in 15 provinces(autonomous regions, municipalities) were selected as the research objects. Nutrition survey was carried out by using 3 consecutive days of 24-hour review method combined with weighing accounting method. Energy and nutrient intake was calculated based on food composition list. The principal component cluster analysis was used to select food groups and K-mean cluster was uesd to extract dietary patterns. Dwass-Steel-Critchlow-Fligner was used to test the difference of food intake in different dietary patterns. Cochran-Armitage trend test was to analyze the change of dietary patterns with the years. Chi-square test was to analyze the difference of people with different dietary patterns in 2018. RESULTS: The dietary patterns of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) were mainly divided into three categories: "traditional rice", "traditional pasta" and "high-quality protein". In 2018, the proportion of "traditional rice" dietary patterns was higher for men than for women, and the proportion of "high-quality protein" dietary patterns was lower than for women. The proportion of "traditional pasta" dietary pattern in people aged 25-35 was higher than that aged 18-24, and the proportion of "high-quality protein" dietary pattern was lower than that aged 18-24. The proportion of people in urban with "traditional rice" dietary pattern was lower than that in rural areas, and the proportion of "high-quality protein" dietary pattern was higher than that in rural areas. The northern region was dominated by "traditional pasta" dietary pattern, while the southern region was dominated by "traditional rice" dietary pattern, and the proportion of people with "high-quality protein" dietary pattern was higher in the northern region than in the southern region. With the increase of education level and income level, the proportion of people with "high-quality protein" dietary pattern showed an increasing trend. From 1989 to 2018, the "traditional rice" dietary pattern had always maintained a high proportion among young people aged 18-35 in 15 provinces(autonomous regions, municipalities) in China, and the "traditional pasta" dietary pattern had been decreasing since 2009, and the "high-quality protein" dietary pattern had significantly increased since 2011. CONCLUSION: From 1989 to 2018, the proportion of young people aged 18-35 with reasonable dietary pattern has increased in 15 provinces(autonomous regions, municipalities), but the traditional dietary pattern still needs to be improved.

Renal fat deposition measured on dixon-based MRI is significantly associated with early kidney damage in obesity.

PURPOSE: To investigate the renal fat deposition on Dixon-based magnetic resonance imaging (MRI) and to explore the predictive value of renal fat biomarkers of magnetic resonance (MR-RFBs) for early kidney damage in obesity. METHODS: This prospective study included 56 obese volunteers and 47 non-obese healthy volunteers. All volunteers underwent renal magnetic resonance examinations. The differences in MR-RFBs [including renal proton density fat fraction (PDFF), renal sinus fat volume (RSFV), and perirenal fat thickness (PRFT)] measured on Dixon-based MRI between the obese and non-obese volunteers were analyzed using a general linear model, taking sex, age, diabetes, and hypertension as covariates. The relationship between estimated glomerular filtration rate (eGFR) and demographic, laboratory, and imaging parameters in obese volunteers was examined by correlation analysis. RESULTS: Obese volunteers had higher MR-RFBs than non-obese volunteers after controlling for confounders (all p < 0.001). Renal PDFF (r = - 0.383; p = 0.004), RSFV (r = - 0.368; p = 0.005), and PRFT (r = - 0.451; p < 0.001) were significantly negatively correlated with eGFR in obesity. After adjusting for age, sex, body mass index, diabetes, hypertension, visceral adipose tissue, subcutaneous adipose tissue, renal PDFF, and RSFV, PRFT remained independently negatively associated with eGFR (ß = - 0.587; p = 0.003). CONCLUSIONS: All MR-RFBs are negatively correlated with eGFR in obesity. The MR-RFBs, especially PRFT, may have predictive value for early kidney damage in obesity.

Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells.

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.

High expression of CCNB2 is an independent predictive poor prognostic biomarker and correlates with immune infiltrates in breast carcinoma.

Background: Cyclin B2 (CCNB2) is associated with cell cycle progression, acting as a cell cycle checkpoint in progression of G2/M transition. In many cancer patients, it has been observed that overexpression of CCNB2 enhances tumor invasiveness and leads to adverse prognosis. However, the association of CCNB2 with the tumor microenvironment remains unclear. Therefore, it is necessary to clarify the associations of CCNB2 with the immune status and prognosis of breast carcinoma (BRCA). Methods: Gene expression and clinical data for BRCA were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, followed by association analyses of CCNB2 expression with prognosis, immune cell infiltration, and immune checkpoints. This study further performed drug sensitivity analysis and constructed a prognostic nomogram for CCNB2. Results: 3619 differentially expressed genes were identified in BRCA, including CCNB2 that emerged as a key gene in the network. High CCNB2 expression correlated with poor prognosis. Functional analysis demonstrated enrichment of CCNB2 co-expressed genes with the cell cycle, cancer progression, cell energy, and immune pathways. Microsatellite instability and tumor mutation burden analyses indicated CCNB2 as a candidate immunotherapy target. Tumor-infiltrating myeloid-derived suppressor cells, regulatory T cells, and T helper 2 cells were associated with CCNB2-related tumor progression and metastasis. CCNB2 expression positively correlated with immune checkpoints, indicating that high CCNB2 expression might facilitate tumor immune escape. Tumors with high CCNB2 expression showed sensitivity to phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin and cyclin-dependent kinase (CDK) 4/6 inhibitors, and the nomogram had good prognostic predictive ability for patients with BRCA. Conclusions: CCNB2 may play a crucial role in tumorigenesis and serve as an independent prognostic biomarker associated with tumor microenvironment, tumor immune infiltration and immunotherapy in BRCA.

Three-dimensional chromatin landscapes in MLLr AML.

Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.

Early identification of postoperative remission for thyrotropin-secreting adenomas.

OBJECTIVE: Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. RESULTS: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. CONCLUSIONS: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

Gas-Phase-Induced Engineering for Fabrication of 3D Hierarchical Porous Nickel and Its Application toward High-Performance Supercapacitors.

Commercial nickel foam (NF), which is composed of numerous interconnected ligaments and hundred-micron pores, is widely acknowledged as a current collector/electrode material for catalysis, sensing, and energy storage applications. However, the commonly used NF often does not work satisfactorily due to its smooth surface and hollow structure of the ligaments. Herein, a gas-phase-induced engineering, two-step gaseous oxidation-reduction (GOR) is presented to directly transform the thin-walled hollow ligament of NF into a three-dimensional (3D) nanoporous prism structure, resulting in the fabrication of a unique hierarchical porous nickel foam (HPNF). This 3D nanoporous architecture is achieved by utilizing the spontaneous reconstruction of nickel atoms during volume expansion and contraction in the GOR process. The process avoids the involution of acid-base corrosion and sacrificial components, which are facile, environmentally friendly, and suitable for large-scale fabrication. Furthermore, MnO2 is electrochemically deposited on the HPNF to form a supercapacitor electrode (HPNF/MnO2). Because of the fully open structure for ion transport, superhydrophilic properties, and the increased contact area between MnO2 and the current collector, the HPNF/MnO2 electrode exhibits a high specific capacitance of 997.5 F g-1 at 3 A g-1 and remarkable cycling stability with 99.6% capacitance retention after 20000 cycles in 0.1 M Na2SO4 electrolyte, outperforming most MnO2-based supercapacitor electrodes.

Comparative Analysis of Post-Translational Modifications of Human Serum Albumin Derived from Human Plasma and Recombinant Sources in China.

BACKGROUND: The variations in sequence, three-dimensional structure, and post-translational modifications (PTMs) of human serum albumin (HSA) are crucial for its physiological functions. This study aims to analyze and compare the disparities in PTMs between HSA derived from human plasma and genetically recombinant sources for clinical treatments in China. METHODS: Six distinct PTMs, namely acetylation, succinylation, crotonylation, phosphorylation, beta-hydroxybutyrylation, and lactylation, were identified using pan-specific antibodies via Western blot analysis. The samples, comprising human plasma-derived HSA (pHSA) from six different manufacturers and recombinant HSA (rHSA) expressed in yeast and Oryza sativa, underwent detection for various types of PTMs. Additionally, a 4D label-free quantitative proteomic analysis was performed to identify N-glycosylation and the aforementioned PTMs in both pHSA and rHSA samples. This analysis aimed to discern disparities in modification sites and levels. RESULTS: Through Western blot analysis, all six pHSA and two rHSA samples displayed positive bands for albumin (66.5 kDa) across the six PTMs. Subsequent analysis using 4D label-free quantitative proteomics revealed 25 (29) acetylated, 30 (32) succinylated, 41 (50) malonylated, 15 (23) phosphorylated, 36 (30) beta-hydroxybutyrylated, and 27 (34) lactylated modification sites in pHSA and rHSA samples, with no N-glycosylation modification sites detected. The analysis identified 1 acetylation (ALB_K160), 2 beta-hydroxybutyrylation (ALB_K569, ALB_K426), and 3 crotonylation (ALB_K264, ALB_K581, ALB_K560) specific modification sites in pHSA, as well as 3 crotonylation (ALB_K560, ALB_K562, ALB_K75), 1 succinylation (ALB_K490), and 23 phosphorylation specific modification sites in rHSA. In pHSA (rHSA), 2 (6) acetylation, 10 (12) succinylation, 0 (9) crotonylation, 1 (9) phosphorylation, 6 (0) beta-hydroxybutyrylation, and 0 (7) lactylation specific modification sites were found. Moreover, in the shared modification sites between pHSA and rHSA, pHSA exhibited up-regulation of amberylation (16:1) and beta-hydroxybutyrylation (12:2) in more sites, and up-regulation of acetylation (7:11), crotonylation (2:11), phosphorylation (1:8), and lactylation (1:14) in fewer sites compared to rHSA. CONCLUSION: In clinical practice, both pHSA and rHSA utilized in China commonly display acetylation, succinylation, crotonylation, phosphorylation, beta-hydroxybutyrylation, and lactylation. Notably, there exist distinctions in the site characteristics and modification levels of these alterations between pHSA and rHSA. Further experimental inquiries are imperative to delve into the implications of these disparities in PTMs on the biological functionality, effectiveness, and safety of pHSA and rHSA.

[Relationship between the percentage of energy intake from macronutrients and obesity among adult residents in 15 provinces of China in 1991-2018].

OBJECTIVE: To explore the relationship between the percentage of energy intake from macronutrients and obesity in Chinese adult residents, and analyze the cut-off values of macronutrients for predicting obesity. METHODS: Data was collected in China Health and Nutrition Survey(CHNS)in 1991-2018. Adults who participated in at least two waves of the surveys and were not obese at baseline were selected as the study subjects. Obesity was defined as body mass index(BMI)≥28.0 kg/m~2. Generalized estimating equation was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and obesity, and receiver operating characteristic curve(ROC) was used to analyze the cut-off values of percentage of energy intake from macronutrients to predict obesity. RESULTS: The percentage of energy intake from protein and fat of adult residents in 15 provinces(autonomous regions and municipalities) in China showed an increasing trend(P<0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend(P<0.01) between 1991 and 2018. After adjusting for covariates, the group of percentage of energy intake from fat in 20%～30%(ß=0.05, 95%CI 0.01-0.08)and ≥30%(ß=0.15, 95%CI 0.11-0.18)were positively correlated with BMI compared with the group of percentage of energy intake from fat <20%, and the risk of obesity in 20%-30% and ≥ 30% was increased by 17%(OR=1.17, 95%CI 1.04-1.31)and 6%(OR=1.06, 95%CI 1.24-1.56), respectively. Compared with the group of the percentage of energy intake from carbohydrate < 50%, the group of 50% to 65%(ß=-0.08, 95% CI-0.11--0.05) and ≥ 65%(ß=-0.17, 95%CI-0.20--0.13) was negatively correlated with BMI, and the percentage of energy intake from carbohydrate ≥ 65% reduced the risk of obesity(OR=0.71, 95%CI 0.63-0.80). CONCLUSION: Carbohydrate intake was inversely correlated with the risk of obesity, and fat intake was positively correlated with the risk of obesity. Moderate intake of carbohydrates and reduced fat intake can prevent obesity.

An individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma.

Pediatric papillary thyroid carcinomas (PPTCs) exhibit high inter-tumor heterogeneity and currently lack widely adopted recurrence risk stratification criteria. Hence, we propose a machine learning-based objective method to individually predict their recurrence risk. We retrospectively collect and evaluate the clinical factors and proteomes of 83 pediatric benign (PB), 85 pediatric malignant (PM) and 66 adult malignant (AM) nodules, and quantify 10,426 proteins by mass spectrometry. We find 243 and 121 significantly dysregulated proteins from PM vs. PB and PM vs. AM, respectively. Function and pathway analyses show the enhanced activation of the inflammatory and immune system in PM patients compared with the others. Nineteen proteins are selected to predict recurrence using a machine learning model with an accuracy of 88.24%. Our study generates a protein-based personalized prognostic prediction model that can stratify PPTC patients into high- or low-recurrence risk groups, providing a reference for clinical decision-making and individualized treatment.

Fish swim bladders as valve leaflets enhance the durability of transcatheter aortic valve replacement devices.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for inoperable patients with severe aortic stenosis (AS). However, calcification-induced limited durability restricts its application. Fish swim bladders (FSB), which are resistant to calcific degeneration, offer a viable solution to this challenge. In this study, we developed a new TAVR device using FSB as the valve leaflet. Furthermore, the in vitro durability, in vivo performance, and size selection of this TAVR device were assessed by an experimental study and finite element analysis. A self-expandable TAVR device was fabricated by suturing the FSB films into a 23 mm nitinol alloy frame. Further, hemodynamic performance, such as effective orifice area, transvalvular pressure difference and regurgitant fraction, the durability was tested by the pulsatile flow test and accelerated fatigue test, according to the ISO 5840-3. The effect of release size on hydrodynamic performance was also investigated. Finally, the in vivo performance of the TAVR device were examined using a porcine implantation model. The results showed that the strength of the FSB films satisfied the requirements for valve leaflets. The hemodynamic performance of the FSB TAVR device met the requirements of ISO 5840-3 standards. After 400 million cycles, the FSB showed no fiber loss, torn, perforation, or other valve failure phenomena. In porcine models, the devices were well-positioned, functioned well with no stenosis immediately after the operation. Collectively, we successfully developed a TAVR device with FSB as valve leaflets that exhibited good fatigue resistance. STATEMENT OF SIGNIFICANCE: The source of material for the leaflets of commercialized biological heart valves (BHVs) is mainly bovine pericardium, but this material suffers the following problems: large and uneven thickness of the material, the presence of α-Gal and Neu5Gc antigens, and the susceptibility to structural valve degradation (SVD). New material for BHVs leaflets is rarely reported. In this study, we prepared a transcatheter aortic valve (TAV) and performed long-term in vitro and short-term in vivo studies using fish swim bladder (FSB) as the leaflets. The study confirmed that FSB TAV device can complete 400 million fatigue tests and maintain the good morphology of the leaflets, and that it still maintains good functionality after a certain amount of compression, indicating that FSB is a promising material for leaflets.

SOD1-high fibroblasts derived exosomal miR-3960 promotes cisplatin resistance in triple-negative breast cancer by suppressing BRSK2-mediated phosphorylation of PIMREG.

Platinum-based neoadjuvant therapy represented by cisplatin is widely employed in treating Triple-Negative Breast Cancer (TNBC), a particularly aggressive subtype of breast cancer. Nevertheless, the emergence of cisplatin resistance presents a formidable challenge to clinical chemotherapy efficacy. Herein, we revealed the critical role of tumor microenvironment (TME) derived exosomal miR-3960 and phosphorylation at the S16 site of PIMREG in activating NF-κB signaling pathway and promoting cisplatin resistance of TNBC. Detailed regulatory mechanisms revealed that SOD1-upregulated fibroblasts secrete miR-3960 and are then transported into TNBC cells via exosomes. Within TNBC cells, miR-3960 targets and inhibits the expression of BRSK2, an AMPK protein kinase family member. Furthermore, we emphasized that BRSK2 contributes to ubiquitination degradation of PIMREG and modulates subsequent activation of the NF-κB signaling pathway by mediating PIMREG phosphorylation at the S16 site, ultimately affects the cisplatin resistance of TNBC. In conclusion, our research demonstrated the crucial role of SOD1high fibroblast, exosomal miR-3960 and S16 site phosphorylated PIMREG in regulating the NF-κB signaling pathway and cisplatin resistance of TNBC. These findings provided significant potential as biomarkers for accurately diagnosing cisplatin-resistant TNBC patients and guiding chemotherapy strategy selection.

USP26 promotes colorectal cancer tumorigenesis by restraining PRKN-mediated mitophagy.

Deubiquitinating enzymes (DUBs) are promising targets for cancer therapy because of their pivotal roles in various physiological and pathological processes. Among these, ubiquitin-specific peptidase 26 (USP26) is a protease with crucial regulatory functions. Our study sheds light on the upregulation of USP26 in colorectal cancer (CRC), in which its increased expression correlates with an unfavorable prognosis. Herein, we evidenced the role of USP26 in promoting CRC tumorigenesis in a parkin RBR E3 ubiquitin-protein ligase (PRKN) protein-dependent manner. Our investigation revealed that USP26 directly interacted with PRKN protein, facilitating its deubiquitination, and subsequently reducing its activity. Additionally, we identified the K129 site on PRKN as a specific target for USP26-mediated deubiquitination. Our research highlights that a K-to-R mutation at the site on PRKN diminishes its potential for activation and ability to mediate mitophagy. In summary, our findings underscore the significance of USP26-mediated deubiquitination in restraining the activation of the PRKN-mediated mitophagy pathway, ultimately driving CRC tumorigenesis. This study not only elucidated the multifaceted role of USP26 in CRC but also introduced a promising avenue for therapeutic exploration through the development of small molecule inhibitors targeting USP26. This strategy holds promise as a novel therapeutic approach for CRC.

Analysis of High-Risk Factors and Construction of a Nomogram Predictive Model for Deep Venous Thrombosis in Pelvic and Acetabular Fracture Patients Treated Conservatively.

PURPOSE: This study aims to develop a predictive nomogram model to assist physicians in making evidence-based decisions and potentially reduce the incidence of deep venous thrombosis (DVT). METHODS: We conducted a retrospective study, including patients admitted to the hospital from January 2014 to January 2022 with a closed, single pelvic or acetabular fracture. Comprehensive data were collected for each patient, encompassing demographics, injury characteristics, comorbidities, and results from laboratory tests and lower extremity ultrasounds. Potential risk factors were identified by univariate and multivariate logistic regression analyses. The predictive model was constructed and then internally validated. Calibration accuracy was assessed using a calibration slope and the Hosmer-Lemeshow goodness-of-fit test. The discrimination of the nomogram model was evaluated using the C-statistic. RESULTS: Out of 232 individuals who underwent conservative treatment, 57 (24.6%) were classified into the DVT group and 175 (75.4%) into the non-DVT group based on lower extremity ultrasound findings. Predominantly, patients were aged between 41 and 65 in both groups. Body mass index (BMI) comparison showed that 54.29% (95/175) of the non-DVT group fell within the healthy weight range, while 45.61% (26/57) in the DVT group were overweight. Notably, the proportion of obesity in the DVT group was more than double that in the non-DVT group, indicating a higher DVT risk with increasing BMI (P=0.0215). Lower red blood cell (RBC) counts were observed in DVT patients compared to non-DVT ones (P<0.001). A similar pattern emerged for D-dimer, a marker for blood clot formation and dissolution, with significant differences noted (P=0.029). Multivariable analysis identified age, BMI, associated organ injury (AOI), American Society of Anesthesiologists score, hemoglobin (HGB), RBC, and D-dimer as candidate predictors. Significant variables included age (OR, 3.04; 95% CI, 1.76-5.26; P<0.001), BMI (OR, 1.97; 95% CI, 1.22-3.18; P=0.006), AOI (OR, 2.05; 95% CI, 1.07-3.95; P=0.031), and HGB (HR, 0.59; 95% CI, 0.39-0.88; P=0.010). The discrimination was 0.787, with a corrected c-index of 0.753. Calibration plots and the Hosmer-Lemeshow test indicated a good fit (P=0.7729). Decision curve analysis revealed a superior net clinical benefit when the predicted probability threshold ranged from 0.05 to 0.95. CONCLUSIONS: We developed a nomogram predictive model, and it could act as a practical tool in clinical workflows to assist physicians in making favorable medical decisions, which potentially reduces the incidence of DVT in those patients with pelvic and acetabular fractures treated conservatively.

A pretrain-finetune approach for improving model generalizability in outcome prediction of acute respiratory distress syndrome patients.

BACKGROUND: Early prediction of acute respiratory distress syndrome (ARDS) of critically ill patients in intensive care units (ICUs) has been intensively studied in the past years. Yet a prediction model trained on data from one hospital might not be well generalized to other hospitals. It is therefore essential to develop an accurate and generalizable ARDS prediction model adaptive to different hospital or medical centers. METHODS: We analyzed electronic medical records of 200,859 and 50,920 hospitalized patients within 24 h after being diagnosed with ARDS from the Philips eICU Institute (eICU-CRD) and the Medical Information Mart for Intensive Care (MIMIC-IV) dataset, respectively. Patients were sorted into three groups, including rapid death, long stay, and recovery, based on their condition or outcome between 24 and 72 h after ARDS diagnosis. To improve prediction performance and generalizability, a "pretrain-finetune" approach was applied, where we pretrained models on the eICU-CRD dataset and performed model finetuning using only a part (35%) of the MIMIC-IV dataset, and then tested the finetuned models on the remaining data from the MIMIC-IV dataset. Well-known machine-learning algorithms, including logistic regression, random forest, extreme gradient boosting, and multilayer perceptron neural networks, were employed to predict ARDS outcomes. Prediction performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Results show that, in general, multilayer perceptron neural networks outperformed the other models. The use of pretrain-finetune yielded improved performance in predicting ARDS outcomes achieving a micro-AUC of 0.870 for the MIMIC-IV dataset, an improvement of 0.046 over the pretrain model. CONCLUSIONS: The proposed pretrain-finetune approach can effectively improve model generalizability from one to another dataset in ARDS prediction.

Accurate preoperative prediction of nodal metastasis in papillary thyroid microcarcinoma: Towards optimal management of patients.

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.

Comprehensive effects of microplastics on algae-laden surface water treatment by coagulation-ultrafiltration combined process: Algae cultivation, coagulation performance and membrane fouling development.

In coastal areas, the surface water has been simultaneously exposed to the algae blooms caused by eutrophication and the microplastics (MPs) pollution originating from active human activities. As a practical alternative to address these issues in drinking water plant, coagulation-ultrafiltration combined process is still confronted with the limited understanding about the comprehensive effects of MPs on algae-laden surface water (ASW) treatment. Considering the migration of MPs in nature environment and drinking water treatment process, this study first aims to systematically investigate the influence of MPs on algae cultivation, coagulation performance and membrane fouling development. The results of algae cultivation indicate that MPs stimulated the algae activity by 58 % and then constantly suppressed the secretion of protein-like, humic-like and polysaccharide-like metabolites. The variation of particle size distribution and zeta potential confirm that MPs acted as nuclei to facilitate the development of large coagulation flocs with an increasing average size from 82.6 µm to 107.6 µm, during which the negatively charged pollutants were neutralized and removed from ASW. According to the SEM images, MPs could destroy the structure of fouling layer on 50 kDa membranes during the filtration of ASW coagulation effluent. Its synergistic effect with the enhanced coagulation performance and the suppressed EOM secretion contributed to the alleviation of membrane fouling caused by overlapped large-sized foulants. However, the interaction between the enriched organic foulants by MPs and the deposited coagulants on 300 kDa membranes facilitated the development of cake layer, leading to the deterioration of membrane permeability. This study emphasizes the importance in concerning the existence of MPs during the treatment of ASW by coagulation-ultrafiltration combined process and their exact influence in water purification efficiency.

Diet Mediate the Impact of Host Habitat on Gut Microbiome and Influence Clinical Indexes by Modulating Gut Microbes and Serum Metabolites.

The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals' gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging-related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.