Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis.

Background: Telomere length, crucial for genomic stability, have been implicated in various inflamm-aging diseases, but their role in sarcoidosis remains unexplored. Objective: This study aims to explore the casual effects between TL and sarcoidosis via a bidirectional Mendelian Randomization (MR) study. Methods: We examined single nucleotide polymorphisms (SNPs) associated with TL and sarcoidosis, utilizing available open-access genome-wide association study (GWAS) databases from the UK Biobank and FinnGen. We employed five MR techniques, including Inverse Variance Weighted (IVW), MR Egger, weighted median (WM), Robust adjusted profile score (RAPS), and Maximum likelihood, to assess causal relationships and explore pleiotropy. Results: Summary data extracted from GWAS datasets of TL (n = 472,174) and (n = 217,758) of European ancestry. Employing 130 SNPs with genome-wide significance as instrumental factors for TL, we detect a significant negative correlation between TL and sarcoidosis (OR: 0.682, 95% confidence interval: 0.524-0.888, p : 0.0045). Similarly, utilizing 6 SNPs with genome-wide significance as instrumental factors for sarcoidosis, we fail to identify a noteworthy association between sarcoidosis and TL (OR: 0.992, 95% confidence interval: 0.979-1.005, p : 0.2424). Conclusion: Our results suggest that longer telomeres may reduce the risk of sarcoidosis, highlighting TL as a potential biomarker for diagnosis and long-term monitoring. Understanding the critical role of telomere shortening enables more effective focus on diagnosing, treating, and curing sarcoidosis linked to telomeres. Clinical investigations into treatments that enhance TL are warranted.

Phosphodiesterase 7 inhibitor reduces stress-induced behavioral and cytoarchitectural changes in C57BL/6J mice by activating the BDNF/TrkB pathway.

Background: Phosphodiesterase 7 (PDE7) plays a role in neurological function. Increased expression and activity of PDE7 has been detected in several central nervous system diseases. However, the role of PDE7 in regulating stress levels remains unclear. Thus, this study aimed to determine whether and how PDE7 involved in the stress-induced behavioral and neuron morphological changes. Methods: The single prolonged stress (SPS) was used to build a stress exposure model in C57BL/6 J mice and detected PDE7 activity in hippocampus, amygdala, prefrontal cortex and striatum. Next, three doses (0.2, 1, and 5 mg/kg) of the PDE7 inhibitor BRL-50481 were intraperitoneally administered for 10 days, then behavioral, biochemical, and morphological tests were conducted. Results: PDE7 activity in hippocampus of mice significantly increased at all times after SPS. BRL-50481 significantly attenuated SPS induced anxiety-like behavior and fear response in both context and cue. In addition, BRL-50481 increased the levels of key molecules in the cAMP signaling pathway which were impaired by SPS. Immunofluorescent staining and Sholl analysis demonstrated that BRL-50481 also restored the nucleus/cytoplasm ratio of hippocampal neurons and improved neuronal plasticity. These effects of BRL-50481 were partially blocked by the TrkB inhibitor ANA-12. Conclusion: PDE7 inhibitors attenuate stress-induced behavioral changes by protecting the neuron cytoarchitecture and the neuronal plasticity in hippocampus, which is mediated at least partly through the activation of BDNF/TrkB signaling pathway. These results proved that PDE7 is a potential target for treating stress-induced behavioral and physiological abnormalities.

Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence: A population-based study.

BACKGROUND: Research on gastrointestinal mucosal adenocarcinoma (GMA) is limited and controversial, and there is no reference tool for predicting postoperative survival. AIM: To investigate the prognosis of GMA and develop predictive model. METHODS: From the Surveillance, Epidemiology, and End Results database, we collected clinical information on patients with GMA. After random sampling, the patients were divided into the discovery (70% of the total, for model training), validation (20%, for model evaluation), and completely blind test cohorts (10%, for further model evaluation). The main assessment metric was the area under the receiver operating characteristic curve (AUC). All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA's prognosis. RESULTS: This model had an AUC of 0.7433 [95% confidence intervals (95%CI): 0.7424-0.7442] in the discovery cohort, 0.7244 (GMA: 0.7234-0.7254) in the validation cohort, and 0.7388 (95%CI: 0.7378-0.7398) in the test cohort. We packaged it into Windows software for doctors' use and uploaded it. Mucinous gastric adenocarcinoma had the worst prognosis, and these were protective factors of GMA: Regional nodes examined [hazard ratio (HR): 0.98, 95%CI: 0.97-0.98, P < 0.001)] and chemotherapy (HR: 0.62, 95%CI: 0.58-0.66, P < 0.001). CONCLUSION: The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively. Combining surgery, chemotherapy, and adequate lymph node dissection during surgery can improve patient outcomes.

Identification of immune-related genes and small-molecule drugs in hypertension-induced left ventricular hypertrophy based on machine learning algorithms and molecular docking.

Background: Left ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs. Materials and methods: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored. Results: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH. Conclusion: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions.

MIKC type MADS-box transcription factor LcSVP2 is involved in dormancy regulation of the terminal buds in evergreen perennial litchi (Litchi chinensis Sonn.).

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

Production of the siderophore lysochelin in rich media through maltose-promoted high-density growth of Lysobacter sp. 3655.

Siderophores are produced by bacteria in iron-restricted conditions. However, we found maltose could induce the biosynthesis of the siderophore lysochelin in Lysobacter sp. 3655 in rich media that are not compatible with siderophore production. Maltose markedly promoted cell growth, with over 300% increase in cell density (OD600) when LB medium was added with maltose (LBM). While lysochelin was not detectable when OD600 in LBM was below 5.0, the siderophore was clearly produced when OD600 reached 7.5 and dramatically increased when OD600 was 15.0. Coincidently, the transcription of lysochelin biosynthesis genes was remarkably enhanced following the increase of OD600. Conversely, the iron concentration in the cell culture dropped to 1.2 µM when OD600 reached 15.0, which was 6-fold lower than that in the starting medium. Moreover, mutants of the maltose-utilizing genes (orf2677 and orf2678) or quorum-sensing related gene orf644 significantly lowered the lysochelin yield. Transcriptomics analysis showed that the iron-utilizing/up-taking genes were up-regulated under high cell density. Accordingly, the transcription of lysochelin biosynthetic genes and the yield of lysochelin were stimulated when the iron-utilizing/up-taking genes were deleted. Finally, lysochelin biosynthesis was positively regulated by a TetR regulator (ORF3043). The lysochelin yield in orf3043 mutant decreased to 50% of that in the wild type and then restored in the complementary strain. Together, this study revealed a previously unrecognized mechanism for lysochelin biosynthetic regulation, by which the siderophore could still be massively produced in Lysobacter even grown in a rich culture medium. This finding could find new applications in large-scale production of siderophores in bacteria.

p-d Orbital Hybridization Induced by Asymmetrical FeSn Dual Atom Sites Promotes the Oxygen Reduction Reaction.

With more flexible active sites and intermetal interaction, dual-atom catalysts (DACs) have emerged as a new frontier in various electrocatalytic reactions. Constructing a typical p-d orbital hybridization between p-block and d-block metal atoms may bring new avenues for manipulating the electronic properties and thus boosting the electrocatalytic activities. Herein, we report a distinctive heteronuclear dual-metal atom catalyst with asymmetrical FeSn dual atom sites embedded on a two-dimensional C2N nanosheet (FeSn-C2N), which displays excellent oxygen reduction reaction (ORR) performance with a half-wave potential of 0.914 V in an alkaline electrolyte. Theoretical calculations further unveil the powerful p-d orbital hybridization between p-block stannum and d-block ferrum in FeSn dual atom sites, which triggers electron delocalization and lowers the energy barrier of *OH protonation, consequently enhancing the ORR activity. In addition, the FeSn-C2N-based Zn-air battery provides a high maximum power density (265.5 mW cm-2) and a high specific capacity (754.6 mA h g-1). Consequently, this work validates the immense potential of p-d orbital hybridization along dual-metal atom catalysts and provides new perception into the logical design of heteronuclear DACs.

Quantification of the Engraftment Status of Mesenchymal Stem Cells in Glioma Using Dual-Modality Magnetic Resonance Imaging and Bioluminescence Imaging.

RATIONALE AND OBJECTIVES: The tumor-tropic properties of mesenchymal stem cells (MSCs) enable them to serve as appealing cellular vehicles for delivering therapeutic agents to treat malignant glioma. However, the exact engraftment status of MSCs in glioma via different administration routes remains unclear due to the lack of quantitative analysis. This study aimed to quantify the engraftment of MSCs in glioma after administration via different routes using non-invasive dual-modality magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). MATERIALS AND METHODS: MSCs were transduced with a lentivirus overexpressing ferritin heavy chain (FTH) and firefly luciferase (FLUC) reporter genes to yield FTH- and FLUC-overexpressed MSCs (FTH-FLUC-MSCs). Wistar rats bearing intracranial C6 glioma received peritumoral, intratumoral, intra-arterial, and intravenous injection of FTH-FLUC-MSCs, respectively. MRI and BLI were performed to monitor FTH-FLUC-MSCs in vivo. RESULTS: FTH-FLUC-MSCs administered via peritumoral, intratumoral and intra-arterial routes migrated specially toward the intracranial glioma in vivo, as detected by MRI and BLI. As quantified by the BLI signal intensity, the percentages of FTH-FLUC-MSCs in the glioma were significantly higher with peritumoral injection (61%) and intratumoral injection (71%) compared to intra-arterial injection (30%) and intravenous injection (0%). Peritumorally injected FTH-FLUC-MSCs showed a gradual decline, with approximately 6% of FTH-FLUC-MSCs still retained within the tumor up to 11 days after injection. Meanwhile, the number of FTH-FLUC-MSCs injected via other routes dropped quickly, and none were detectable by day 11 post-injection. CONCLUSION: Peritumoral delivery of FTH-FLUC-MSCs offers robust engraftment and could be used as the optimal delivery route for treating malignant glioma.

Trophic effects of jellyfish blooms on fish populations in ecosystems of the coastal waters of China.

Jellyfish play an important role in the material cycling and energy flow of food webs, and massive aggregations may have deleterious consequences for local fisheries; yet a theoretical framework of the trophic effects of jellyfish blooms on coastal fisheries is unclear. To address this knowledge gap, we assessed the trophic interactions between cooccurring bloom jellyfish and dominant fish groups (omnivorous fish and piscivorous fish) in the coastal waters of China (CWC) via stable isotope analysis; we subsequently discussed how jellyfish blooms may affect energy flow through coastal ecosystems. Our results indicate a considerable degree of trophic overlap (mean ratio > 65 %) between jellyfish and small omnivorous fish (< 10 cm), highlighting a similarity in feeding habits, while the overlap ratio decreased to <55 % of the large omnivorous fish group (> 10 cm). Relatively higher trophic levels and smaller overlaps of large omnivorous fish were found in the ecosystem with high jellyfish biomass, which suggested that they may reinforce the ontogenetic trophic shift pattern to alleviate the potential for resource competition with jellyfish under conditions of jellyfish explosion. The smallest trophic overlap (< 20 %) highlighted the strong trophic differentiation between jellyfish and piscivorous fish. Additionally, our study suggested that a massive aggregation of jellyfish can negatively influence zooplankton but may not transfer energy further up efficiently, implying a weak trophic coupling between jellyfish and upper-trophic levels in CWC ecosystems. Thus, we speculate that jellyfish play an important role in shaping pathways involved in the energy transfer of food webs and that large blooms may negatively affect fisheries through bottom-up control affecting prey availability. In general, these results hold strong potential to further improve the understanding of the trophic interactions between jellyfish and fish populations. Furthermore, this study provides valuable data for predicting the consequences of jellyfish blooms on ecosystems, and is crucial for ecosystem-based management of coastal fisheries.

Investigating the mechanism of PAD in the treatment of acne based on network pharmacology and molecular docking: A review.

Acne is a common and chronic skin condition characterized by high incidence, recurrent symptoms and difficult cure. Summarizing the clinical treatment experience, it was found that the powder for ascending and descending was effective in the treatment of acne. Our aim was to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of powder for ascending and descending against acne. First, the chemical components and target genes of PAD were sifted using the TCMSP and HERB database. The targets of acne were obtained simultaneously from the CTD, OMIM and GeneCards database. The obtained drug targets and disease targets were imported into the R language software to draw Venn diagrams. Then, the potential targets were imported into the String website to construct a protein interaction network diagram. And Cytoscape software was used for topological analysis to screen the core targets, and the core targets were analyzed by GO functional enrichment and KEGG pathway enrichment. Finally, molecular docking was used to verify the predictions of key genes' reliability. The core targets of the treatment of acne were TNF, GADPH, IL-6 and so on. The results of enrichment analysis showed that the treatment of acne with PAD may be related to TNF signaling pathway and AGE-RAGE signaling pathway. The molecular docking verification showed that the components were well bound to the core targets of acne, and the docking ability of stigmasterol and TNF (-12.73 kcal/mol) was particularly outstanding.

Is three-dimensional ultrasonography a valuable diagnostic tool for patients with ovarian cancer? Systematic review and meta-analysis.

Introduction: This paper was to assess the diagnostic performance and clinical value of three-dimensional ultrasonography (3DUS), three-dimensional ultrasonography power Doppler (3DPD), and 3DUS combined with 3DPD in ovarian cancer (OC). Methods: The study was registered with PROSPERO (CRD 42023405765). PubMed and Web of Science were searched from inception to 25 January 2022, and reference lists of potentially eligible studies were also manually searched. Patient and study characteristics were extracted by two independent reviewers. Any discrepancies were addressed through discussion. The sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR, respectively), and the area under the receiver operating characteristic curve (AUC) were pooled separately. Results: We retrieved 2,566 studies, of which 18 were finally enrolled, with 2,548 cases. The pooled sensitivity, specificity, PLR, NLR, and AUC for 3DUS were 0.89 (95% CI: 0.85-0.93), 0.93 (95% CI: 0.88-0.96), 13.1 (95% CI: 7.3-23.4), 0.11 (95% CI: 0.08-0.16), and 0.90 (95% CI: 0.87-0.93), respectively. The pooled sensitivity, specificity, PLR, NLR, and AUC for 3DPD were 0.90 (95% CI: 0.80-0.95), 0.85 (95% CI: 0.71-0.92), 5.8 (95% CI: 3.0-11.2), 0.12 (95% CI: 0.06-0.24), and 0.94 (95% CI: 0.91-0.96), respectively. The pooled sensitivity, specificity, PLR, NLR, and AUC for 3DUS combined with 3DPD were 0.99 (95% CI: 0.73-1.00), 0.95 (95% CI: 0.85-0.99), 21.9 (95% CI: 6.1-78.9), 0.01 (95% CI: 0.00-0.37), and 0.99 (95% CI: 0.98-1.00), respectively. Conclusions: 3DUS, 3DPD, and 3DUS combined with 3DPD are promising diagnostic tools for OC, alongside elevated sensitivity and specificity. However, the combination of 3DUS and 3DPD techniques has higher diagnostic efficiency. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42023405765.

Identification of novel dual-target 4-hydroxyphenylpyruvate dioxygenase & phytoene dehydrogenase inhibitors via multiple virtual screening.

Two important plant enzymes are 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27), which is necessary for biosynthesis of plastoquinone and tocopherols, and phytoene dehydrogenase (PDS; EC 1.3.99.26), which plays an important role in colour rendering. Dual-target proteins that inhibit pigment synthesis will prevent resistant weeds and improve the spectral characteristics of herbicides. This study introduces virtual screening of pharmacophores based on the complex structure of the two targets. A three-dimensional database was established by screening 1,492,858 compounds based on the Lipinski principle. HPPD&PDS dual-target receptor-ligand pharmacophore models were then constructed, and nine potential dual-target inhibitors were obtained through pharmacophore modeling, molecular docking, and molecular dynamics simulations. Ultimately, ADMET prediction software yielded three compounds with high potential as dual-target herbicides. The obtained nine inhibitors were stable when combined with both HPPD and PDS proteins. This study offers guidance for the development of HPPD&PDS dual-target inhibitors with novel skeletons.

Deciphering the Dual Roles of an Alginate-Based Biodegradable Flocculant in Anaerobic Fermentation of Waste Activated Sludge: Dewaterability and Degradability.

Biodegradable flocculants are rarely used in waste activated sludge (WAS) fermentation. This study introduces an alginate-based biodegradable flocculant (ABF) to enhance both the dewatering and degradation of WAS during its fermentation. Alginate was identified in structural extracellular polymeric substances (St-EPS) of WAS, with alginate-producing bacteria comprising ∼4.2% of the total bacterial population in WAS. Owing to its larger floc size, higher contact angle, and lower free energy resulting from the Lewis acid-base interaction, the addition of the prepared ABF with a network structure significantly improved the dewaterability of WAS and reduced capillary suction time (CST) by 72%. The utilization of ABF by an enriched alginate-degrading consortium (ADC) resulted in a 35.5% increase in the WAS methane yield owing to its higher hydrolytic activity on both ABF and St-EPS. Additionally, after a 30 day fermentation, CST decreased by 62% owing to the enhanced degradation of St-EPS (74.4%) and lower viscosity in the WAS + ABF + ADC group. The genus Bacteroides, comprising 12% of ADC, used alginate lyase (EC 4.2.2.3) and pectate lyase (EC 4.2.2.2 and EC 4.2.2.9) to degrade alginate and polygalacturonate in St-EPS, respectively. Therefore, this study introduces a new flocculant and elucidates its dual roles in enhancing both the dewaterability and degradability of WAS. These advancements improve WAS fermentation, resulting in higher methane production and lower CSTs.

Dual role of PpV in Drosophila crystal cell proliferation and survival.

Drosophila melanogaster crystal cells are a specialized type of blood cells for innate immune process upon injury. Under normal conditions, crystal cells rarely proliferate and constitute a small proportion of fly blood cells. Notch signaling has been known to guide the cell fate determination of crystal cells and maintain their survival. Here, we reported that protein phosphatase V (PpV), the unique catalytic subunit of protein phosphatase 6 in Drosophila, is a novel regulator of crystal cell proliferation and integrity. We found that PpV proteins highly accumulated in crystal cells in the larval hematopoietic organ termed the lymph gland. Silencing PpV using RNA interference led to increased crystal cell proliferation in a Notch-independent manner and induced crystal cell rupture dependent on Notch signaling. Moreover, additive PpV prevented the rupture of crystal cells in lymph glands upon a needle injury, suggesting the involvement of PpV in wound healing. Altogether, our results indicated that PpV plays a dual role in lymph glands, preventing crystal cell proliferation to limit the cell number, as well as inhibiting crystal cell rupture to maintain their survival.

Puerarin Attenuates Insulin Resistance by Inhibiting Endoplasmic Reticulum Stress and Suppresses Inflammation by Modulating the JNK and IKKß/NF-κB Pathways in Epididymal White Adipose Tissue of Mice on a High-Fat Diet.

SCOPE: Obesity is associated with insulin resistance (IR), which is characterized by endoplasmic reticulum (ER) stress in multiple organs. ER stress in adipose tissue causes metabolic disturbances and activates inflammatory signaling pathways. Puerarin, an isoflavone extracted from Pueraria lobata, exhibits antioxidant, anti-inflammatory, and antidiabetic effects. This study explores the potential mechanisms underlying puerarin's role in mitigating insulin resistance in high-fat diet (HFD)-induced obese mice. METHODS AND RESULTS: In this study, insulin resistant in mice is induced by a high-fat diet, followed by treatment with puerarin. The results demonstrate that puerarin effectively attenuates insulin resistance, including weight loss, improvement of glucose tolerance and insulin sensitivity, and activation of insulin signaling pathway. Additionally, puerarin administration suppresses ER stress by down-regulation of ATF6, ATF4, CHOP, GRP78 expressions in epididymal white adipose tissue (eWAT), along with decreased phosphorylation IRE1α, PERK, and eIF2α. Furthermore, puerarin exerts anti-inflammatory effects by inhibiting JNK and IKKß/NF-κB pathways, leading to reduction of TNF-α and IL-6. CONCLUSION: These findings suggest that puerarin mitigates insulin resistance by inhibiting ER stress and suppressing inflammation through the JNK and IKKß/NF-κB pathways. This highlights the promising clinical application of puerarin in the treatment of insulin resistance.

A Bimetallic Electro-Sensitizer Improves ROS Therapy by Relieving Autophagy-Induced ROS Tolerance and Immune Suppression.

Reactive oxygen species (ROS)-dependent monotherapy usually demonstrates poor therapeutic outcomes, due to the accompanied activation of protective autophagy in tumor cells, which results in ROS tolerance and immune suppression. In this study, a bimetallic electro-sensitizer, Pt-Ir NPs is constructed, loaded with the autophagy inhibitor chloroquine (Pt-Ir-CQ NPs), to enhance the effectiveness of electrotherapy by inhibiting autophagy and activating anti-tumor immune responses. This novel electrotherapy platform demonstrates unique advantages, particularly in the treatment of hypoxic and immunosuppressive tumors. First, the electro-sensitizer catalyzes water molecules into ROS under electric field, achieving tumor ablation through electrotoxicity. Second, the incorporated CQ inhibits the protective autophagy induced by electrotherapy, restoring the sensitivity of tumor cells to ROS and thereby enhancing the anti-tumor effects of electrotherapy. Third, Pt-Ir-CQ NPs enhance the functionality of antigen-presenting cells and immunogenic cells through inhibiting autophagy, synergistically activating the anti-tumor immune responses along with the immunogenic cell death (ICD) effect induced by electrotherapy. This study provides a novel approach for the effective ablation and long-term inhibition of solid tumors through flexible modulation by an exogenous electric field.

Prenatal diagnosis and family analysis of 17q12 microdeletion syndrome with fetal renal abnormalities.

Purpose: To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome. Methods: We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents. Results: Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia. Conclusion: Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT).

Skinned Motion Retargeting with Preservation of Body Part Relationships.

Motion retargeting is an active research area in computer graphics and animation, allowing for the transfer of motion from one character to another, thereby creating diverse animated character data. While this technology has numerous applications in animation, games, and movies, current methods often produce unnatural or semantically inconsistent motion when applied to characters with different shapes or joint counts. This is primarily due to a lack of consideration for the geometric and spatial relationships between the body parts of the source and target characters. To tackle this challenge, we introduce a novel spatially-preserving Skinned Motion Retargeting Network (SMRNet) capable of handling motion retargeting for characters with varying shapes and skeletal structures while maintaining semantic consistency. By learning a hybrid representation of the character's skeleton and shape in a rest pose, SMRNet transfers the rotation and root joint position of the source character's motion to the target character through embedded rest pose feature alignment. Additionally, it incorporates a differentiable loss function to further preserve the spatial consistency of body parts between the source and target. Comprehensive quantitative and qualitative evaluations demonstrate the superiority of our approach over existing alternatives, particularly in preserving spatial relationships more effectively.

Comparative study on chemical constituents of different medicinal parts of Lonicera japonica Thunb. Based on LC-MS combined with multivariate statistical analysis.

Lonicerae japonicae flos (LJF), Lonicerae japonicae caulis (LJC), Lonicerae folium (LF) and Lonicerae fructus (LFR) are derived from Lonicera japonica Thunb., which are formed due to different medicinal parts. The efficacy of the 4 medicinal materials has similarities and differences. However, little attention has been paid to illustrate the differences in efficacy from the perspective of phytochemistry. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive-Orbitrap-MS) was used to qualitatively analyze the ingredients in 4 herbs. A total of 86 compounds were plausibly or unambiguously identified, there were 54 common components among the 4 medicinal materials, and each kind of medicinal materials had its own unique components. On the basis of qualitative analysis, ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was used to quantitatively analyze 31 components contained in 4 medicinal materials, and principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical analysis were furtherly performed for comparing the component contents. The results showed that the samples from the same parts were clustered into one group, and the samples from different medicinal parts were significantly different. The analysis of variable importance projection (VIP) value of the OPLS-DA model showed that 10 components including chlorogenic acid, secologanic acid, isochlorogenic acid A, loganin, lonicerin, loganic acid, secoxyloganin, sweroside, luteolin and rhoifolin were the main difference components among the 4 medicinal materials. The study not only lays a solid foundation for the intrinsic quality control of 4 medicinal materials and the study of different effects of the 4 medicinal materials at the phytochemical level, but also provides a basis for more rational utilization of various parts of L. japonica and expansion of medicinal resources.