Radiomics analysis for prediction and classification of submucosal tumors based on gastrointestinal endoscopic ultrasonography.

Objectives: To identify and classify submucosal tumors by building and validating a radiomics model with gastrointestinal endoscopic ultrasonography (EUS) images. Methods: A total of 144 patients diagnosed with submucosal tumors through gastrointestinal EUS were collected between January 2019 and October 2020. There are 1952 radiomic features extracted from each patient's EUS images. The statistical test and the customized least absolute shrinkage and selection operator regression were used for feature selection. Subsequently, an extremely randomized trees algorithm was utilized to construct a robust radiomics classification model specifically tailored for gastrointestinal EUS images. The performance of the model was measured by evaluating the area under the receiver operating characteristic curve. Results: The radiomics model comprised 30 selected features that showed good discrimination performance in the validation cohorts. During validation, the area under the receiver operating characteristic curve was calculated as 0.9203 and the mean value after 10-fold cross-validation was 0.9260, indicating excellent stability and calibration. These results confirm the clinical utility of the model. Conclusions: Utilizing the dataset provided curated from gastrointestinal EUS examinations at our collaborating hospital, we have developed a well-performing radiomics model. It can be used for personalized and non-invasive prediction of the type of submucosal tumors, providing physicians with aid for early treatment and management of tumor progression.

[Clinical effects of percutaneous elastic intramedullary nail assisted by arthrography for the treatment of radial neck fractures in children].

OBJECTIVE: To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children. METHODS: A retrospective analysis was performed on 23 children with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation (arthrography with elastic nail group) from January 2019 to December 2022, including 12 males and 11 females, aged from 2 to 12 years old with an average of (7.36±1.89) years old;According to Judet fracture types, 14 children were type Ⅲ and 9 children were type Ⅳ. In addition, 23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation (elastic nail group), including 11 males and 12 females, aged from 2 to 14 years old with an average of (7.50±1.91) years old;Judet classification included 15 children were type Ⅲ and 8 children were type Ⅳ. Operative time and intraoperative fluoroscopy times were compared between two groups. Metaizeau evaluation criteria was used to evaluate fracture reduction, and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups. RESULTS: Both groups were followed up for 12 to 24 months with an average of (16.56±6.34) months. Operative time and intraoperative fluoroscopy times of elastic nail group were (56.64±19.27) min and (21.13±7.87) times, while those of joint angiography with elastic nail group were (40.33±11.50) min and (12.10±3.52) times;there were difference between two groups (P<0.05). According to Metaizeau evaluation, 11 patients got excellent result, 9 good and 3 fair in joint angiography with elastic nail group, while in elastic nail group, 5 excellent, 13 good, 4 acceptable, and 1 poor;the difference between two groups was statistically significant (P<0.05). According to Tibone-Stoltz criteria, 14 patients got excellent result, 8 good, and 1 fair in joint arthrography with elastic nail group;while in elastic nail group, 12 patients got excellent result, 9 good, 1 fair and 1 poor;there was no significant difference between two groups (P>0.05). CONCLUSION: Compared to percutaneous elastic intramedullary nail fixation, closed reduction assisted by arthrography has advantages of reduced operation time, decreased intraoperative fluoroscopy frequency, and improved fracture reduction. Arthrography enables clear visualization of the anatomical structures of radius, head, neck, bone, and cartilage in children, facilitating comprehensive display of fracture reduction and brachioradial joint alignment. This technique more precisely guides the depth of elastic intramedullary nail implantation in radius neck, thereby enhancing surgical efficiency and success rate.

Effects and mechanisms of Polygonati Rhizoma polysaccharide on potassium oxonate and hypoxanthine-induced hyperuricemia in mice.

Hyperuricemia, a prevalent metabolic disturbance intricately linked to gout and chronic kidney disease (CKD), may be relieved by traditional Chinese medicine Polygonati Rhizoma. It is derived from the rhizomes of Polygonatum sibiricum, Polygonatum kingianum, and Polygonatum cyrtonema, which are rich in polysaccharides and are effective hyperuricemia alleviators. This study investigated the potential of Polygonatum sibiricum polysaccharide (PSP) in managing hyperuricemia. PSP (125, 250, and 500 mg/kg, i.g.) or allopurinol was administered to hyperuricemia mice treated with potassium oxonate and hypoxanthine for two weeks. PSP effectively decreased serum uric acid levels by inhibiting xanthine oxidase and adenosine deaminase activity and expression in the liver and modulating uric acid-related transporters (URAT1, OAT1, and OAT3) in the kidney. PSP lowered serum creatinine and blood urea nitrogen levels, alleviating hyperuricemia-induced renal tubular epithelial-mesenchymal fibrosis. In vitro, PSP promoted mitochondrial biogenesis via the PGC-1α/NRF1/TFAM pathway, suppressed reactive oxygen species production, and prevented cytochrome C and dynamin-related protein 1 dysregulation in HK-2 cells. Furthermore, PSPA (Mw 4.0 kDa) and PSPB (Mw 112.2 kDa) isolated from PSP exhibit different uric acid-lowering mechanisms. In conclusion, our findings highlight the therapeutic potential of PSP and its nephroprotective effects in hyperuricemia, thereby supporting its development as a therapeutic agent for hyperuricemia.

A machine-learning prediction model to identify risk of firearm injury using electronic health records data.

IMPORTANCE: Firearm injuries constitute a public health crisis. At the healthcare encounter level, they are, however, rare events. OBJECTIVE: To develop a predictive model to identify healthcare encounters of adult patients at increased risk of firearm injury to target screening and prevention efforts. MATERIALS AND METHODS: Electronic health records data from Kaiser Permanente Southern California (KPSC) were used to identify healthcare encounters of patients with fatal and non-fatal firearm injuries, as well as healthcare visits of a sample of matched controls during 2010-2018. More than 170 predictors, including diagnoses, healthcare utilization, and neighborhood characteristics were identified. Extreme gradient boosting (XGBoost) and a split sample design were used to train and test a model that predicted risk of firearm injury within the next 3 years at the encounter level. RESULTS: A total of 3879 firearm injuries were identified among 5 288 529 KPSC adult members. Prevalence at the healthcare encounter level was 0.01%. The 15 most important predictors included demographics, healthcare utilization, and neighborhood-level socio-economic factors. The sensitivity and specificity of the final model were 0.83 and 0.56, respectively. A very high-risk group (top 1% of predicted risk) yielded a positive predictive value of 0.14% and sensitivity of 13%. This high-risk group potentially reduces screening burden by a factor of 11.7, compared to universal screening. Results for alternative probability cutoffs are presented. DISCUSSION: Our model can support more targeted screening in healthcare settings, resulting in improved efficiency of firearm injury risk assessment and prevention efforts.

Combinations of HDAC inhibitor and PPAR agonist induce ferroptosis of leukemic stem cell-like cells in acute myeloid leukemia.

PURPOSE: Leukemia stem cells (LSCs) are responsible for leukemia initiation, relapse, and therapeutic resistance. Therefore, the development of novel therapeutic approaches targeting LSCs is urgently needed for patients with AML. METHODS: The LSCs-like cell lines (KG-1α and Kasumi-1), CD34+ primary AML cells purified from AML patients (n=23) treated with CS055 and/or chiglitazar and were analyzed for viability, death, and colony formation assay. We performed RNA-seq, Glutamate-Release, Intracellular-GSH, Lipid-ROS, transmission-electron-microscopy, Western-Blotting assay, and confirmed ferroptosis in LSCs-like cells. The luciferase-reporter, co-immunoprecipitation, HDAC3-shRNA/HDAC3/deacetylase-deficient LSCs-like cell lines, His-pull-down, and chromatin-immunoprecipitation assays performed to clarify the molecular mechanism of CS055/chiglitazar in LSCs-like cells. We also established CDX and PDX mouse models to evaluate the therapeutic efficacy of CS055/chiglitazar against-AML in vivo. RESULTS: We report that the histone deacetylase inhibitor CS055, in combination with peroxisome proliferator-activated receptor (PPAR) pan-agonist (chiglitazar), synergistically targets leukemia stem-like cells from leukemia cell lines and patient samples, while sparing normal hematopoietic progenitor cells. Mechanistically, chiglitazar enhances the inhibitory effect of CS055 on HDAC3 and induces ferroptosis in LSCs-like cells by down-regulating the expression of ferroptosis suppressor SLC7A11. In fact, the inhibition of HDAC3 increases H3K27AC levels in the promoter region of activating transcription factor 3 (ATF3), a transcriptional repressor of the SLC7A11 gene, and upregulates the expression of ATF3. In contrast, ATF4, a SLC7A11 activator, is suppressed by HDAC3 inhibition. CONCLUSIONS: Our findings suggest that treatment with CS055 combined with chiglitazar, will target LSCs by inducing ferroptosis and may confer an effective approach for the treatment of AML.

Role of calcium salts in modulating benzo[a]pyrene levels in barbecued pork sausages: A study on quality attributes and safety.

Benzo[a]pyrene (BaP), known for its carcinogenic and mutagenic properties, is a marker of polycyclic aromatic hydrocarbons (PAHs). This study aimed to investigate the effect of partially replacing sodium chloride with different calcium salts (calcium chloride, calcium gluconate, calcium citrate, and calcium lactate) on BaP formation in barbecued pork sausages. The results revealed that all four calcium salts inhibited BaP formation in barbecued pork sausages (P < 0.05). Specifically, calcium gluconate showed the most significant effect on BaP inhibition, with an inhibition rate of 61.82 %. Furthermore, calcium salts were found to inhibit lipid oxidation in barbecued pork sausages while promoting the Maillard reaction. Further validation experiments used resveratrol and sodium sulfite as lipid oxidation and Maillard reaction inhibitors, respectively. These results indicated that lipid oxidation is the primary pathway for BaP production in barbecued pork sausage and that the addition of calcium salts can effectively block this process.

Enhanced Long-Term Cycling Life of Ni-Rich NMC Cathodes in High-Voltage Lithium-Metal Batteries.

Li metal batteries (LMBs) have revived people's interest due to their high energy density. This work compares the cycling stability, structure stability, and thermal stability of Li||0.7Nb-NMC 9055 (0.7% Nb-modified LiNi0.9Co0.05Mn0.05O2) system in commercial carbonate electrolyte (1.0 M LiPF6 in EC/DMC) and designed carbonate electrolyte (1.0 M LiPF6-0.125 M LiNO3-0.025 M Mg(TFSI)2 in FEC-EMC). Li||0.7Nb-NMC 9055 battery with designed carbonate electrolyte exhibited superior capacity retention, 80% after ∼500 cycles. This can be explained by the improved mechanical integrity of the secondary particles and large reduced charge transfer resistance. Further, the real-time thermal monitoring of full cell via a high-precision, multimode calorimeter TAM IV Micro XL shows that the designed carbonate electrolyte with multisalt additive and FEC cosolvent has less heat release during the charging and discharge process, allowing these high-nickel (Ni) cathodes to reach closer to their full potential.

The effects of mindfulness enhanced Tai Chi Chuan training on mental and physical health among beginners: a randomized controlled trial.

Introduction: Tai Chi Chuan (TCC) is a traditional Chinese mind-body exercise widely adopted in Chinese communities and colleges. However, the mindful essence of TCC is rarely emphasized during popularization. This makes it difficult for beginners to benefit from it. The present study aimed to examine the effects of a Mindfulness-enhanced Tai Chi Chuan (MTCC) intervention, which enhances mindfulness components embedded within TCC, on mental and physical health among beginners. Methods: A randomized controlled trial was conducted with 119 healthy college students new to Tai Chi Chuan training. Participants were assigned to either the MTCC group or the TCC group. Both interventions consisted of 10 weekly 90-min training sessions, with the MTCC group emphasizing and enhancing mindfulness components. Outcome measures included mindfulness, depression, anxiety, stress, and physical fitness, assessed at baseline and post-intervention. Results: The results showed that the MTCC group had significantly greater improvements than the TCC group in mindfulness, anxiety, stress, and health-and skill-related physical fitness. There were no significant differences between the two groups in depression. Conclusion: The findings suggest that compared to TCC, MTCC can effectively promote individuals' physical fitness and provide additional benefits to mental well-being. MTCC can be recommended as an accessible and beneficial intervention for beginners to improve mental health and strengthen their bodies. Clinical review registration: https://www.chictr.org.cn/, identifier ChiCTR2200058175.

Unconjugated bilirubin promotes uric acid restoration by activating hepatic AMPK pathway.

Hyperuricemia and its development to gout have reached epidemic proportions. Systemic hyperuricemia is facilitated by elevated activity of xanthine oxidase (XO), the sole source of uric acid in mammals. Here, we aim to investigate the role of bilirubin in maintaining circulating uric acid homeostasis. We observed serum bilirubin concentrations were inversely correlated with uric acid levels in humans with new-onset hyperuricemia and advanced gout in a clinical cohort consisting of 891 participants. We confirmed that bilirubin biosynthesis impairment recapitulated traits of hyperuricemia symptoms, exemplified by raised circulating uric acid levels and accumulated hepatic XO, and exacerbated mouse hyperuricemia development. Bilirubin administration significantly decreased circulating uric acid levels in hyperuricemia-inducing (HUA) mice receiving potassium oxonate (a uricase inhibitor) or fed with a high fructose diet. Finally, we proved that bilirubin ameliorated mouse hyperuricemia by increasing hepatic autophagy, restoring antioxidant defense and normalizing mitochondrial function in a manner dependent on AMPK pathway. Hepatocyte-specific AMPKα knockdown via adeno-associated virus (AAV) 8-TBG-mediated gene delivery compromised the efficacy of bilirubin in HUA mice. Our study demonstrates the deficiency of bilirubin in hyperuricemia progression, and the protective effects exerted by bilirubin against mouse hyperuricemia development, which may potentiate clinical management of hyperuricemia.

Classification of diabetic retinopathy algorithm based on a novel dual-path multi-module model.

Diabetic retinopathy is a chronic disease of the eye that is precipitated via diabetes. As the disease progresses, the blood vessels in the retina are issue to modifications such as dilation, leakage, and new blood vessel formation. Early detection and treatment of the lesions are vital for the prevention and reduction of imaginative and prescient loss. A new dual-path multi-module network algorithm for diabetic retinopathy classification is proposed in this paper, aiming to accurately classify the diabetic retinopathy stage to facilitate early diagnosis and intervention. To obtain the purpose of fact augmentation, the algorithm first enhances retinal lesion features using color correcting and multi-scale fusion algorithms. It then optimizes the local records via a multi-path multiplexing structure with convolutional kernels of exclusive sizes. Finally, a multi-feature fusion module is used to improve the accuracy of the diabetic retinopathy classification model. Two public datasets and a real hospital dataset are used to validate the algorithm. The accuracy is 98.9%, 99.3%, and 98.3%, respectively. The experimental results not only confirm the advancement and practicability of the algorithm in the field of automatic DR diagnosis, but also foretell its broad application prospects in clinical settings, which is expected to provide strong technical support for the early screening and treatment of diabetic retinopathy.

Asymptomatic multicentric Castleman disease: A potential early stage of idiopathic MCD.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

[Zhongfeng Xingnao Decoction alleviates intracerebral haemorrhage-induced brain injury via inhibiting neuronal ferroptosis].

Zhongfeng Xingnao Decoction(ZFXN) has been utilized for treating intracerebral hemorrhage(ICH) in China, while the pharmacological mechanism of ZFXN remains unclear. Exploring the pharmacological roles of ZFXN is critical for guiding the treatment of cerebrovascular diseases. In this study, a rat model of ICH was constructed by injection of Ⅶ collagenase in the right caudate nucleus. SD rats were randomly assigned into five groups, and the neurological function of rats was evaluated based on the Bederson score. Magnetic resonance imaging(MRI) was used to assess the volume of ICH. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to observe the pathological and ultrastructural changes in the brain tissue. The levels of reactive oxygen species(ROS) were measured by flow cytometry. The immunofluorescence assay was employed to detect the expression of glutathione peroxidase 4(GPX4) in neurons surrounding the hematoma. Finally, Western blot was employed to determine the expression of ferroptosis-related proteins upstream frameshift 1(UPF1), ferroportin(FPN), acyl-CoA ligase 4(ACSL4), cyclooxyge-nase-2(COX-2), GPX4, NADPH oxidase 1(NOX1), and solute carrier family 7 member 11(SLC7A11) after ICH. Compared with the model(ICH) group, ZFXN treatment for 5 days attenuated neurological dysfunction, reduced the hematoma volume, and alleviated the pathological changes induced by ICH. Meanwhile, ZFXN lowered the levels of Fe~(2+) and oxidative stress and up-regulated the expression of proteins inhibiting ferroptosis. ZFXN improved the prognosis of ICH in rats by inhibiting neuronal ferroptosis, which provided a valuable guide for the clinical application of ZFXN. ZFXN may inhibit ferroptosis by promoting the expression of SLC7A11 and FPN.

Efficient Inhibition of Ice Recrystallization During Frozen Storage: Based on the Diffusional Suppression Effect of Silk Fibroin.

Effectively controlling ice recrystallization (IR) during the frozen storage of food remains highly challenging. Inspired by the structural characteristics of antifreeze proteins in nature, silk fibroin (SF) derived from silk fibers has been developed. Through dual validation using the "splat" assay and "sucrose sandwich" assay, the IR inhibition activity of SF at various concentrations was confirmed, revealing that its regular alternating hydrophilic/hydrophobic domains endow SF with the potential to inhibit the axial growth of single ice crystal and significantly reduce the average maximum crystal size by approximately 67%. Additionally, the quality stability of frozen muscle foods treated with SF was comprehensively evaluated. In stark contrast to traditional commercial antifreeze agents (4% sucrose and 4% sorbitol), prepared steaks with the addition of 2% SF maintained rich juiciness and excellent color acceptability over a three-month frozen storage period. Thus, SF holds promise as a potential protective agent for frozen muscle foods, enhancing their quality during storage.

Kaempferol attenuates cyclosporine-induced renal tubular injury via inhibiting the ROS-ASK1-MAPK pathway.

Cyclosporine (CSA) is a widely used immunosuppressive medication. CSA nephrotoxicity severely limits its application. Kaempferol (KPF), a naturally occurring phenolic compound, has a promising protective effect in reducing CSA-induced renal tubular injury, but the mechanism remains unknown. Our study aimed to determine the protective role of KPF against CSA-induced renal tubular injury. C57/B6 mice and the NRK-52E cell line were employed. CSA worsened renal function in mice, causing detachment and necrosis of tubular cells, leading to tubular vacuolation and renal interstitial fibrosis. CSA caused the detachment, rupture, and death of tubular cells in vitro, resulting in cell viability loss. KPF mitigated all these injurious alterations. KPF hindered CSA-induced ROS generation and protected renal tubular epithelial cells, similar to the antioxidant NAC. CSA lowered SOD activity and GSH levels while increasing MDA levels, and KPF ameliorated these changes. CSA caused phosphorylation of ASK1, JNK, and p38, similar to H2O2, whereas KPF significantly inhibited these changes. In conclusion, KPF reduces CSA-induced tubular epithelial cell injury via its antioxidant properties, inhibits the phosphorylation of ASK1, and inhibits the phosphorylation of p38 and JNK, implying that the synergistic use of KPF in CSA immunotherapy may be a promising option to reduce CSA-evoked renal injury.

Loncastuximab tesirine in Chinese patients with relapsed or refractory diffuse large B-cell lymphoma: a multicenter, open-label, single-arm, phase II trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

[Effects of different genotypes soybean and maize intercropping on soil phosphorus fractions and crop phosphorus uptake]. / ä¸åŒåŸºå› åž‹å¤§è±†ä¸ŽçŽ‰ç±³é—´ä½œå¯¹åœŸå£¤ç£·ç»„åˆ†ä¸Žä½œç‰©ç£·å¸æ”¶çš„å½±å“.

Reasonable soybean-maize intercropping mode can effectively promote soil phosphorus turnover and crop phosphorus absorption, and reduce phosphorus fertilizer input. To optimize phosphorus (P)-use efficiency in soybean/maize intercropping system, we intercropped two genotypes of soybean with maize to investigate the rhizosphere processes and mechanisms underlying soil biological P fractions and crop P uptake. The results showed that intercropping significantly depleted the rhizosphere soluble inorganic P (CaCl2-P) content in soybean genotype Yuechun 03-3, without impact on the P fractions in the rhizosphere of soybean Essex. Similarly, intercropping significantly increased biomass and P uptake of soybean genotype Yuechun 03-3 by 42.2% and 46.9%, respectively, compared to monoculture. However, it did not affect P uptake and biomass of soybean Essex and maize. Intercropping significantly increased both the total root length and the quantity of root exudates in Yuechun 03-3 by 19.7% and 138.1%, respectively. There was a significant positive correlation between P uptake and total root length in Yuechun 03-3, while a significant negative correlation between soluble inorganic P content and P uptake. In summary, intercropping of soybean and maize exhibited noticeable genotype differences in its impact on soil P fractions and crop P uptake. Intercropping has the potential to improve soybean P uptake and rhizosphere P turnover, mainly by increasing root length and root exudates of P-efficient genotype. The study would provide scientific evidence for optimizing the pairing of soybean and maize varieties in intercropping systems, thereby enhancing phosphorus utilization efficiency and reducing fertilizer inputs.

TRIM59 is required for mouse GC-1 cell maintenance through modulating the ubiquitination of AXIN1.

Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate ß-catenin signaling. Furthermore, activation of ß-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

Genome-wide identification and expression analysis of the SPL gene family and its response to abiotic stress in barley (Hordeum vulgare L.).

BACKGROUND: Squamosa promoter-binding protein-like (SPL) is a plant-specific transcription factor that is widely involved in the regulation of plant growth and development, including flower and grain development, stress responses, and secondary metabolite synthesis. However, this gene family has not been comprehensively evaluated in barley, the most adaptable cereal crop with a high nutritional value. RESULTS: In this study, a total of 15 HvSPL genes were identified based on the Hordeum vulgare genome. These genes were named HvSPL1 to HvSPL15 based on the chromosomal distribution of the HvSPL genes and were divided into seven groups (I, II, III, V, VI, VII, and VIII) based on the phylogenetic tree analysis. Chromosomal localization revealed one pair of tandem duplicated genes and one pair of segmental duplicated genes. The HvSPL genes exhibited the highest collinearity with the monocotyledonous plant, Zea mays (27 pairs), followed by Oryza sativa (18 pairs), Sorghum bicolor (16 pairs), and Arabidopsis thaliana (3 pairs), and the fewest homologous genes with Solanum lycopersicum (1 pair). The distribution of the HvSPL genes in the evolutionary tree was relatively scattered, and HvSPL proteins tended to cluster with SPL proteins from Z. mays and O. sativa, indicating a close relationship between HvSPL and SPL proteins from monocotyledonous plants. Finally, the spatial and temporal expression patterns of the 14 HvSPL genes from different subfamilies were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Based on the results, the HvSPL gene family exhibited tissue-specific expression and played a regulatory role in grain development and abiotic stress. HvSPL genes are highly expressed in various tissues during seed development. The expression levels of HvSPL genes under the six abiotic stress conditions indicated that many genes responded to stress, especially HvSPL8, which exhibited high expression under multiple stress conditions, thereby warranting further attention. CONCLUSION: In this study, 15 SPL gene family members were identified in the genome of Hordeum vulgare, and the phylogenetic relationships, gene structure, replication events, gene expression, and potential roles of these genes in millet development were studied. Our findings lay the foundation for exploring the HvSPL genes and performing molecular breeding of barley.

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.