Absence of motor impairments or pathological changes in TMEM230 knockout rats.

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. In addition, no glial reactions were observed in TMEM230 knockout rats. These results indicate that depletion of TMEM230 may not lead to dopaminergic neuron degeneration in rats, further supporting that PD-associated TMEM230 mutations lead to dopaminergic neuron death by gain-of-toxic function.

Erratum: [Corrigendum] ACSM3 suppresses proliferation and induces apoptosis and cell cycle arrest in acute myeloid leukemia cells via the regulation of IGF2BP2.

[This corrects the article DOI: 10.3892/etm.2023.11876.].

High Expression of SRSF10 Promotes Colorectal Cancer Progression by Aberrant Alternative Splicing of RFC5.

BACKGROUND: Colorectal cancer (CRC) remains a global health concern with persistently high incidence and mortality rates. However, the specific pathogenesis of CRC remains poorly understood. This study aims to investigate the role and pathogenesis of serine and arginine rich splicing factor 10 (SRSF10) in colorectal cancer. METHODS: Bioinformatics analysis was employed to predict SRSF10 gene expression in CRC patients. Functional experiments involving SRSF10 knockdown and overexpression were conducted using CCK8, transwell, scratch assay, and flow cytometry. Additionally, the PRIdictor website was utilized to predict the SRSF10 interaction site with RFC5. The identification of different transcripts of SRSF10-acting RFC5 pre-mRNA was achieved through agarose gel electrophoresis. RESULT: The knockdown of SRSF10 inhibited the proliferation and migration ability of CRC cells, while promoting apoptosis and altering the DNA replication of CRC cells. Conversely, when SRSF10 was highly expressed, it enhanced the proliferation and migration ability of CRC cells and caused changes in the cell cycle of colorectal cancer cells. This study revealed a change in the replicating factor C subunit 5 (RFC5) gene in colorectal cancer cells following SRSF10 knockdown. Furthermore, it was confirmed that SRSF10 increased RFC5 exon2-AS1(S) transcription variants, thereby promoting the development of colorectal cancer through AS1 exclusion to exon 2 of RFC5. CONCLUSION: In summary, this study demonstrates that SRSF10 promotes the progression of colorectal cancer by generating an aberrantly spliced exclusion isoform of AS1 within RFC5 exon 2. These findings suggest that SRSF10 could serve as a crucial target for the clinical diagnosis and treatment of CRC.

Aloe polysaccharides ameliorate obesity-associated cognitive dysfunction in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.

Aloe polysaccharides (APs) display cognition-improving properties, but the underlying mechanisms remain unclear. Herein, AP supplementation for 24 weeks significantly improved cognitive behavioral disturbances caused by a high-fat diet. Moreover, APs notably reshaped the structure of the gut microbiota, which was manifested by increasing the relative abundance of Alloprevotella, Alistipes, Romboutsia, Turicibacter, Prevotellaceae_UCG-001, and Akkermansia while reducing the abundance of Parasutterella, Staphylococcus, Helicobacter, Enterococcus, and Erysipelatoclostridium. Notably, the gut barrier damage and LPS leakage caused by HF were recovered by APs. Additionally, with the improvement of intestinal barrier integrity, oxidative stress and inflammation in the brain and jejunum were significantly ameliorated. Furthermore, the expression of genes associated with cognitive impairment and the intestinal tract barrier was up-regulated (CREB, BDNF, TrkB, ZO-1 and occludin), while the expression of genes associated with inflammatory factors was down-regulated (IL-1ß, IL-6, and TNF-α). Finally, we observed a significant correlation among cognition-related genes, gut microbiota, oxidative stress, and inflammation in the HF-AP group. Together, our findings suggest that altered gut microbiota composition and improved gut barrier integrity may be important targets for potentially improving high-fat diet-induced cognitive impairment.

The role of tissue-derived extracellular vesicles in tumor microenvironment.

The tumor microenvironment (TME) is a highly heterogeneous ecosystem that plays critical roles in the initiation, progression, invasion, and metastasis of cancers. Extracellular vesicles (EVs), as emerging components of the host-tumor communication, are lipid-bilayer membrane structures that are secreted by most cell types into TEM and increasingly recognized as critical elements that regulate the interaction between tumor cells and their surroundings. They contain a variety of bioactive molecules, such as proteins, nucleic acids, and lipids, and participate in various pathophysiological processes while regulating intercellular communication. While many studies have focused on the EVs derived from different body fluids or cell culture supernatants, the direct isolation of tissue-derived EVs (Ti-EVs) has garnered more attention due to the advantages of tissue specificity and accurate reflection of tissue microenvironment. In this review, we summarize the protocol for isolating Ti-EVs from different tissue interstitium, discuss the role of tumor-derived and adipose tissue-derived Ti-EVs in regulating TME. In addition, we sum up the latest application of Ti-EVs as potential biomarkers for cancer diseases.

Synthesizing Si/SiOC composites through different sol-gel reaction routes for lithium-ion battery anode materials.

Silicon oxycarbide (SiOC) exhibits good retention and a reasonable specific capacity and is an alternative to silicon used as an anode material for high-performance lithium-ion batteries. However, SiOC generally shows a low Initial Coulombic Efficiency (ICE), wasting the lithium from the cathode. This work explores different sol-gel routes to synthesize SiOC from silanes and compares their performance. We found that the crushed bulk acid-catalyzed SiOC is simple and cost-effective but with excellent performance. Adding dimethyldimethoxysilane (DMDMS) by decreasing the oxygen content further enhances the battery performance. Building upon the excellent performance of SiOC, we further embed nano-silicon into SiOC. The Si/SiOC composites achieved a significantly higher specific capacity of 2185 mAhg-1 and an impressive ICE of 77 % with acceptable battery retention.

Spiky tubular nanoparticles with low protein corona can realize efficient and non-destructive penetration through endothelial barrier.

Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy and the morphology were designed for pursuing high drug loading capacity. Compared to solid and mesoporous NPs, we found the spiky tubular NPs facilitated to reserve the NPs' antifouling properties (or shedding of "protein corona"), promoted better endothelial penetration and less destruction in vitro and in vivo. This could be attributed to that those multiple spikes on spiky tubular NPs limited the NP-protein interaction area and promoted the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy, while it lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of endothelia. As a result, these NPs have advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Our finding here suggests that we could exploit the surface morphological modification to design spiky tubular NPs, to improve the NP delivery efficiency while prohibiting the leakiness of vascular endothelial microenvironment, particularly relevant for tumor migration during nanomedicine applications in cancer therapy.

A novel betapartitivirus isolated from Cordyceps militaris, an edible-medicinal mushroom.

In this study, we identified a novel partitivirus, named "Cordyceps militaris partitivirus 1" (CmPV1), in Cordyceps militaris strain RCEF7506. The complete genome of CmPV1 comprises two segments, dsRNA1 and dsRNA2, each encoding a single protein. dsRNA1 (2,206 bp) encodes an RNA-dependent RNA polymerase (RdRp), and dsRNA2 (2,256 bp) encodes a coat protein (CP). Sequence analysis revealed that dsRNA1 has the highest similarity to that of Bipolaris maydis partitivirus 2 (BmPV2), whereas dsRNA2 shows the highest similarity to human blood-associated partitivirus (HuBPV). Phylogenetic analysis based on RdRp sequences suggests that CmPV1 is a new member of the genus Betapartitivirus of the family Partitiviridae. This is the first documentation of a betapartitivirus infecting the entomopathogenic fungus C. militaris.

Analysis of the associations between moderate-to-vigorous physical activity and screen time on psychological symptoms among university students: a cross-sectional survey based on six geographic regions in China.

BACKGROUND: Declining physical activity and increasing screen time (ST) among Chinese adolescents have become major concerns shared by scholars, while mental health issues are also on the rise. Previous studies have confirmed the association between physical activity and screen time and psychological symptoms, but it is unclear how their psychological symptoms, especially for Chinese university students who have a high proportion of psychological symptoms, and no research evidence has been found. METHODS: This study investigated physical activity, screen time, and psychological symptoms in 11,173 university students aged 19-22 years in six regions of China. A binary logistic regression analysis was used to analyze the association between moderate-to-vigorous physical activity (MVPA) and screen time and psychological symptoms. And the generalize linear model (GLM) analysis was used to further analyze the association between MVPA and screen time and psychological symptoms. RESULTS: The detection rate of psychological symptoms among Chinese university students was 16.3%, with a higher percentage of female students (17.5%) than male students (14.7%). The proportion of male students (8.2%) with MVPA > 60 min/d was higher than that of female students (2.3%), and the proportion of male students (33.8%) and female students (34.5%) with screen time > 2 h/d was basically the same. The generalize linear model (GLM) analysis showed that university students with MVPA < 30 min/d and screen time > 2 h/d (OR = 1.59, 95% CI: 1.10-2.31) had the highest risk of psychological symptoms (OR = 1.59, 95% CI: 1.10-2.31) compared to university students with MVPA > 60 min/d and screen time < 1 h/d as the reference group. The risk of psychological symptoms was the highest among those with MVPA < 30 min/d and screen time > 2 h/d (OR = 1.59,95% CI: 1.10-2.31). In addition, university students with MVPA > 60 min/d and a screen time of 1-2 h/d (OR = 0.09, 95% CI: 0.03-0.25) had the lowest risk of psychological symptoms (P < 0.001). The same trend was observed for both male and female students. CONCLUSION: Chinese university students have a certain proportion of psychological symptom problems, and there is a significant between MVPA and screen time and psychological symptoms, and the same trend exists for both male and female students. Chinese university students should perform MVPA for not less than 60 min a day, and at the same time control the duration of screen time, and screen time should be controlled between 1 and 2 h a day, which has a better promotion effect on psychological health.

Brain metastasis magnetic resonance imaging-based deep learning for predicting epidermal growth factor receptor (EGFR) mutation and subtypes in metastatic non-small cell lung cancer.

Background: The preoperative identification of epidermal growth factor receptor (EGFR) mutations and subtypes based on magnetic resonance imaging (MRI) of brain metastases (BM) is necessary to facilitate individualized therapy. This study aimed to develop a deep learning model to preoperatively detect EGFR mutations and identify the location of EGFR mutations in patients with non-small cell lung cancer (NSCLC) and BM. Methods: We included 160 and 72 patients who underwent contrast-enhanced T1-weighted (T1w-CE) and T2-weighted (T2W) MRI at Liaoning Cancer Hospital and Institute (center 1) and Shengjing Hospital of China Medical University (center 2) to form a training cohort and an external validation cohort, respectively. A multiscale feature fusion network (MSF-Net) was developed by adaptively integrating features based on different stages of residual network (ResNet) 50 and by introducing channel and spatial attention modules. The external validation set from center 2 was used to assess the performance of MSF-Net and to compare it with that of handcrafted radiomics features. Receiver operating characteristic (ROC) curves, accuracy, precision, recall, and F1-score were used to evaluate the effectiveness of the models. Gradient-weighted class activation mapping (Grad-CAM) was used to demonstrate the attention of the MSF-Net model. Results: The developed MSF-Net generated a better diagnostic performance than did the handcrafted radiomics in terms of the microaveraged area under the curve (AUC) (MSF-Net: 0.91; radiomics: 0.80) and macroaveraged AUC (MSF-Net: 0.90; radiomics: 0.81) for predicting EGFR mutations and subtypes. Conclusions: This study provides an end-to-end and noninvasive imaging tool for the preoperative prediction of EGFR mutation status and subtypes based on BM, which may be helpful for facilitating individualized clinical treatment plans.

Genomic profiling of biosynthetic potentials of medicinal secondary metabolites for 'Aliisedimentitalea scapharcae' KCTC 42119T, isolated from ark shell.

Microorganisms living with higher organisms are valuable sources of bioactive substances like antibiotics, which could assist them competing for more and better nutrients or space. Here, we focused on a marine animal-associated bacterium, 'Aliisedimentitalea scapharcae' KCTC 42119T, which was isolated from ark shell collected from Gang-Jin bay of South Korea. We evaluated its biosynthetic potentials of medicinal secondary metabolites by de novo genome sequencing. The complete genome of strain KCTC 42119T sequenced is 5,083,900 bp and is comprised of one circular chromosome and four circular plasmids. Functional genome analysis by antiSMASH v7.1.0 showed that there are nine biosynthetic gene clusters encoded on the chromosome. The annotated secondary metabolites include antibiotic corynecin, cytoprotective ectoine and antineoplastic ET-743 (Yondelis), which suggested strain KCTC 42119T possesses potentials to synthesize a series of secondary metabolites of pharmaceutical utility. Genome analysis of 'A. scapharcae' also provides more insights into mining bioactive substances from animal-associated microorganisms.

Multiple collapses of blastocysts after full blastocyst formation is an independent risk factor for aneuploidy - a study based on AI and manual validation.

BACKGROUND: The occurrence of blastocyst collapse may become an indicator of preimplantation embryo quality assessment. It has been reported that collapsing blastocysts can lead to higher rates of aneuploidy and poorer clinical outcomes, but more large-scale studies are needed to explore this relationship. This study explored the characteristics of blastocyst collapse identified and quantified by artificial intelligence and explored the associations between blastocyst collapse and embryo ploidy, morphological quality, and clinical outcomes. METHODS: This observational study included data from 3288 biopsied blastocysts in 1071 time-lapse preimplantation genetic testing cycles performed between January 2019 and February 2023 at a single academic fertility center. All transferred blastocysts are euploid blastocysts. The artificial intelligence recognized blastocyst collapse in time-lapse microscopy videos and then registered the collapsing times, and the start time, the recovery duration, the shrinkage percentage of each collapse. The effects of blastocyst collapse and embryo ploidy, pregnancy, live birth, miscarriage, and embryo quality were studied using available data from 1196 euploid embryos and 1300 aneuploid embryos. RESULTS: 5.6% of blastocysts collapsed at least once only before the full blastocyst formation (tB), 19.4% collapsed at least once only after tB, and 3.1% collapsed both before and after tB. Multiple collapses of blastocysts after tB (times ≥ 2) are associated with higher aneuploid rates (54.6%, P > 0.05; 70.5%, P < 0.001; 72.5%, P = 0.004; and 71.4%, P = 0.049 in blastocysts collapsed 1, 2, 3 or ≥ 4 times), which remained significant after adjustment for confounders (OR = 2.597, 95% CI 1.464-4.607, P = 0.001). Analysis of the aneuploid embryos showed a higher ratio of collapses and multiple collapses after tB in monosomies and embryos with subchromosomal deletion of segmental nature (P < 0.001). Blastocyst collapse was associated with delayed embryonic development and declined blastocyst quality. There is no significant difference in pregnancy and live birth rates between collapsing and non-collapsing blastocysts. CONCLUSIONS: Blastocyst collapse is common during blastocyst development. This study underlined that multiple blastocyst collapses after tB may be an independent risk factor for aneuploidy which should be taken into account by clinicians and embryologists when selecting blastocysts for transfer.

The therapeutic and biomarker significance of ferroptosis in chronic myeloid leukemia.

Background: The relationship between ferroptosis and the progression and treatment of hematological tumors has been extensively studied, although its precise association with chronic myeloid leukemia (CML) remains uncertain. Methods: Multi-transcriptome sequencing data were utilized to analyze the ferroptosis level of CML samples and its correlation with the tumor microenvironment, disease progression, and treatment response. Machine learning algorithms were employed to identify diagnostic ferroptosis-related genes (FRGs). The consensus clustering algorithm was applied to identify ferroptosis-related molecular subtypes. Clinical samples were collected for sequencing to validate the results obtained from bioinformatics analysis. Cell experiments were conducted to investigate the therapeutic efficacy of induced ferroptosis in drug-resistant CML. Results: Ferroptosis scores were significantly lower in samples from patients with CML compared to normal samples, and these scores further decreased with disease progression and non-response to treatment. Most FRGs were downregulated in CML samples. A high ferroptosis score was also associated with greater immunosuppression and increased activity of metabolic pathways. Through support vector machine recursive feature elimination (SVM-RFE), least absolute shrinkage selection operator (LASSO), and random forest (RF) algorithms, we identified five FRGs (ACSL6, SLC11A2, HMOX1, SLC38A1, AKR1C3) that have high diagnostic value. The clinical diagnostic value of these five FRGs and their effectiveness in differentiating CML from other hematological malignancies were validated using additional validation cohorts and our real-world cohort. There are significant differences in immune landscape, chemosensitivity, and immunotherapy responsiveness between the two ferroptosis-related molecular subtypes. By conducting cellular experiments, we confirmed that CML-resistant cells are more sensitive to induction of ferroptosis and can enhance the sensitivity of imatinib treatment. Conclusion: Our study unveils the molecular signature of ferroptosis in samples from patients with CML. FRG identified by a variety of machine learning algorithms has reliable clinical diagnostic value. Furthermore, the characterization of different ferroptosis-related molecular subtypes provides valuable insights into individual patient characteristics and can guide clinical treatment strategies. Targeting and inducing ferroptosis holds great promise as a therapeutic approach for drug-resistant CML.

The density of the inner cell mass is a new indicator of the quality of a human blastocyst: a valid supplement to the Gardner scoring system.

STUDY QUESTION: Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst? SUMMARY ANSWER: The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth. WHAT IS KNOWN ALREADY: In evaluating the quality of ICM, reproductive care clinics still use size indicators without further evaluation. The main disadvantage of this current method is that the evaluation of blastocyst ICM is relatively rough and cannot meet the needs of clinical embryologists, especially when multiple blastocysts have the same ICM score, which makes them difficult to evaluate further. STUDY DESIGN, SIZE, DURATION: This observational study included data from 2272 blastocysts in 1991 frozen-thawed embryo transfer (FET) cycles between January 2018 to November 2021 and 1105 blastocysts in 430 preimplantation genetic testing cycles between January 2019 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: FET, ICSI, blastocyst culture, trophectoderm biopsy, time-lapse (TL) monitoring, and next-generation sequencing were performed. After preliminary sample size selection, the 11 focal plane images captured by the TL system were normalized and the spatial frequency was used to construct the DI of the ICM. MAIN RESULTS AND THE ROLE OF CHANCE: This study successfully constructed a quantitative indicator DI that can reflect the degree of ICM density in terms of fusion and texture features. The higher the DI value, the better the density of the blastocyst ICM, and the higher the chances that the blastocyst was euploid (P < 0.001) and that pregnancy (P < 0.001) and live birth (P = 0.005) were reached. In blastocysts with ICM graded B and blastocysts graded 4BB, DI was also positively associated with ploidy, pregnancy, and live birth (P < 0.05). ROC analysis showed that combining the Gardner scoring system with DI can more effectively predict pregnancy and live births, when compared to using the Gardner scoring system alone. LIMITATIONS, REASONS FOR CAUTION: Accurate calculation of the DI value places high demands on image quality, requiring manual selection of the clearest focal plane and exposure control. Images with the ICM not completely within the field of view cannot be used. The association between the density of ICM and chromosomal mosaicism was not evaluated. The associations between the density of ICM and different assisted reproductive technologies and different culture conditions in embryo laboratories were also not evaluated. Prospective studies are needed to further investigate the impact of ICM density on clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: ICM density assessment is a new direction in blastocyst assessment. This study explores new ways of assessing blastocyst ICM density and develops quantitative indicators and a corresponding qualitative evaluation scheme for ICM density. The DI of the blastocyst ICM developed in this study is easy to calculate and requires only TL equipment and image processing, providing positive guidance for clinical outcomes. The qualitative evaluation scheme of ICM density can assist embryologists without TL equipment to manually evaluate ICM density. ICM density is a simple indicator that can be used in practice and is a good complement to the blastocyst scoring systems currently used in most centers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Portraying on-road CO2 concentrations using street view panoramas and ensemble learning.

A significant reduction in carbon dioxide (CO2) emissions caused by transportation is essential for attaining sustainable urban development. Carbon concentrations from road traffic in urban areas exhibit complex spatial patterns due to the impact of street configurations, mobile sources, and human activities. However, a comprehensive understanding of these patterns, which involve complex interactions, is still lacking due to the human perspective of road interface characteristics has not been taken into account. In this study, a mobile travel platform was constructed to collect both on-road navigation Street View Panoramas (OSVPs) and the corresponding CO2 concentrations. >100 thousand sample pairs that matched "street view-CO2 concentration" were obtained, covering 675.8 km of roads in Shenzhen, China. In addition, four ensemble learning (EL) models were utilized to establish nonlinear connections between the semantic and object features of streetscapes and CO2 concentrations. After performing EL fusion modeling, the predictive R2 in the test set exceeded 90 %, and the mean absolute error (MAE) was <3.2 ppm. The model was applied to Baidu Street View Panoramas (BSVPs) in Shenzhen to generate a map of average on-road CO2 with a 100 m resolution, and the Local Indicator of Spatial Association (LISA) was then used to identify high CO2 intensity spatial clusters. Additionally, the Light Gradient Boost-SHapley Additive exPlanation (LGB-SHAP) analysis revealed that vertically planted trees can reduce CO2 emissions from on-road sources. Moreover, the factors that affect on-road CO2 exhibit interaction and threshold effects. Street View Panoramas (SVPs) and Artificial Intelligence (AI) were adopted here to enhance the spatial measurement of on-road CO2 concentrations and the understanding of driving factors. Our approach facilitates the assessment and design of low-emission transportation in urban areas, which is critical for promoting sustainable traffic development.

Interference with PLA2G16 promotes cell cycle arrest and apoptosis and inhibits the reprogramming of glucose metabolism in multiple myeloma cells by modulating the Hippo/YAP signaling pathway.

Multiple myeloma, which is a clonal plasma cell tumor, derives from a postmitotic lymphoid B-cell lineage and remains untreatable. Group XVI phospholipase A2 (PLA2G16) can either be a tumor suppressor or an oncogene in different types of cancer. This study was intended to explore the role of PLA2G16 in multiple myeloma and to reveal the reaction mechanism. The mRNA and protein expressions of PLA2G16 in human bone marrow stromal cell line HS-5 and multiple myeloma cells were assessed using reverse transcription-quantitative PCR and western blot. The transfection efficacy of sh-PLA2G16 and oe-YAP was examined using reverse transcription-quantitative PCR and western blot. Through cell counting kit-8 assay and 5-ethynyl-2'- deoxyuridine staining, multiple myeloma cell viability and proliferation were detected. Flow cytometry was used to measure cell apoptosis and cell cycle distribution. Oxygen consumption rate, the activities of mitochondrial respiratory chain complexes I-V, and the activity of caspase-3 were estimated with Seahorse XF24 analyzer, oxidative phosphorylation activity assay kit, and caspase-3 assay kit, respectively. Lactate production and glucose consumption were evaluated usingcorresponding assay kits. Western blot was employed to meaure proteins associated with cell cycle, glycolysis, pentose phosphate pathway as well as Hippo/YAP signaling pathway. In this study, PLA2G16 expression was greatly increased in multiple myeloma cells and PLA2G16 silence inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle arrest, and suppressed the reprogramming of glucose metabolism in multiple myeloma. It was also identified that PLA2G16 depletion inhibited the Hippo/YAP signaling pathway. Further experiments revealed that the overexpression of YAP partially reversed the inhibitory effects of PLA2G16 silence on multiple myeloma cell malignant development and the reprogramming of glucose metabolism. Collectively, PLA2G16 silence impeded multiple myeloma progression and inhibited glucose metabolism reprogramming by blocking the Hippo/YAP signaling pathway.

Reappraisal and refined diagnosis of ultrasonography and histological findings for hydatidiform moles: a multicentre retrospective study of 821 patients.

AIMS: Specific identification of a hydatidiform mole (HM) and subclassification of a complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) are critical. This study aimed to reappraise the diagnostic performance of ultrasonography and histology with a refined diagnosis. METHODS: This was a retrospective, multicentre cohort study of 821 patients with histologically suspected HM specimens. Refined diagnostic algorithms with p57 immunohistochemistry and short tandem repeat (STR) genotyping were performed and used as the true standard for assessing the diagnostic performance of the original ultrasonography and morphology methods. The diagnostic performance was calculated using accuracy, agreement rate, sensitivity and the positive predictive value (PPV) compared with refined diagnostic results. RESULTS: Of the 821 histologically suspected HM cases included, 788 (95.98%) were successfully reclassified into 448 CHMs, 213 PHMs and 127 non-molar (NM) abortuses. Ultrasonography showed an overall accuracy of 44.38%, with a sensitivity of 44.33% for CHM and 37.5% for PHM. The overall classification accuracy of the original morphological diagnosis was 65.97%. After exclusion of the initially untyped HMs, the overall agreement rate was 59.11% (κ=0.364, p<0.0001) between the original and refined diagnoses, with a sensitivity of 40.09% and PPV of 96.05% for diagnosing CHMs and a sensitivity of 84.98% and a PPV of 45.59% for diagnosing PHMs. The interinstitutional variability of morphology in diagnosing HMs was significant among the 15 centres (range, 8.33%-100.00%, p<0.0001). CONCLUSION: The current diagnosis of HM based solely on ultrasound or morphology remains problematic, and ancillary techniques, particularly p57 immunohistochemistry and DNA genotyping, should be integrated into routine practice as much as possible.

The learning curve of laparoscopic splenectomy and esophagogastric devascularization for portal hypertension with 10-year follow-up.

INTRODUCTION AND OBJECTIVES: Laparoscopic splenectomy and esophagogastric devascularization (LSED) are minimally invasive, effective, and safe in treating esophageal-fundic variceal bleeding with portal hypertension (PHT). The study aimed to assess the learning curve of LSED by cumulative summation (CUSUM) analysis. The 10-year follow-up data for LSED and open surgery were also examined. PATIENTS AND METHODS: Five hundred and ninety-four patients were retrospectively analyzed. Operation time, intraoperative blood loss, open operation conversion, and postoperative complications were selected as the evaluation indicators of surgical ability. The learning curve of LESD was assessed by the CUSUM approach. Patient features, perioperative indices, and 10-year follow-up data were examined. RESULTS: Totally 236 patients underwent open surgery, and 358 underwent LSED. Patient characteristics were similar between groups. The LSED patients experienced less intraoperative blood loss, fewer complications, and faster recovery compared to the open surgery cohort. The learning curve of LESD was maximal for a case number of 50. Preoperative general characteristics were comparable for both stages. But the skilled stage had decreased operation time, reduced blood loss, less postoperative complications, and better recovery compared to the learning stage. The LSED group had higher recurrent hemorrhage-free survival rate and increased overall survival in comparison with cases administered open surgery in the 10-year follow-up. Free-liver cancer rates were similar between two groups. CONCLUSIONS: About 50 cases are needed to master the LSED procedure. Compared to open surgery, LSED is a safer, feasible, and safe procedure for PHT patients, correlating with decreased rebleeding rate and better overall survival.

Mechanical performance and anisotropic analysis of rubberised 3D-printed concrete incorporating PP fibre.

The research investigates the effects of substituting sand with rubber particles derived from waste tyres-up to 40% by volume-and the inclusion of polypropylene (PP) fibres. Unlike steel fibres, which can cause operational challenges and surface irregularities in the printing process, PP fibres' flexibility integrates well within the concrete matrix. This integration ensures smooth extrusion and a high-quality surface finish, enhancing the printability of the concrete. The study's findings reveal that including rubber particles and PP fibres impacts the concrete's properties, showing a general decline in compressive and flexural strengths as the rubber content increases. Nevertheless, the PP fibre-enhanced mixtures maintain sufficient structural strength, demonstrating an anisotropic compressive strength above 30 MPa and a flexural strength of 4 MPa. These results underscore the feasibility of using rubberised 3D-printed concrete with PP fibres in sustainable construction practices, aligning with standards (ACI 318:2018) and contributing to eco-friendly and innovative construction methodologies.