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Diaphragm valves play a crucial role in controlling fluid flow in piping systems, and their hydraulic performance directly impacts system efficiency. This study employs numerical simulations using OpenFOAM v8 to investigate the hydraulic characteristics of a diaphragm valve, focusing on the effects of inlet boundary conditions and turbulence models on head loss. At the maximum valve opening, two inlet conditions of OpenFOAM, flowRateInletVelocity and timeVaryingMappedFixedValue, were compared. Results show that the flowRateInletVelocity inlet condition yields simulation results in excellent agreement with experimental data, validating its reliability. Five turbulence models (Standard k-ε, Realizable k-ε, RNG k-ε, SST k-ω, and Spalart-Allmaras) were evaluated, revealing that the SST k-ω model offers the highest computational accuracy in capturing flow field details and head loss, while the Spalart-Allmaras model demonstrates significant discrepancies. Further analysis under varying valve openings and flow rates identifies an exponential relationship between head loss and value opening, with the most pronounced changes occurring below 50% opening. These findings provide a theoretical basis for optimizing diaphragm valve designs and enhancing the accuracy of CFD simulations in hydraulic engineering applications.

Class IV ddaC neurons specifically prune larval dendrites without affecting axons during Drosophila metamorphosis. ddaCs distribute the minus ends of microtubules (MTs) to dendrites but the plus ends to axons. However, a requirement of MT minus-end-binding proteins in dendrite-specific pruning remains completely unknown. Here, we identified Patronin, a minus-end-binding protein, for its crucial and dose-sensitive role in ddaC dendrite pruning. The CKK domain is important for Patronin’s function in dendrite pruning. Moreover, we show that both patronin knockdown and overexpression resulted in a drastic decrease of MT minus ends and a concomitant increase of plus-end-out MTs in ddaC dendrites, suggesting that Patronin stabilizes dendritic minus-end-out MTs. Consistently, attenuation of Klp10A MT depolymerase in patronin mutant neurons significantly restored minus-end-out MTs in dendrites and thereby rescued dendrite-pruning defects. Thus, our study demonstrates that Patronin orients minus-end-out MT arrays in dendrites to promote dendrite-specific pruning mainly through antagonizing Klp10A activity. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter ).

Cannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster , or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of two important sensory regulators Poxn and Orco. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.

Refinement of the nervous system depends on selective removal of excessive axons/dendrites, a process known as pruning. Drosophila ddaC sensory neurons prune their larval dendrites via endo-lysosomal degradation of the L1-type cell adhesion molecule (L1-CAM), Neuroglian (Nrg). Here, we have identified a novel gene, pruning defect 1 (prd1), which governs dendrite pruning of ddaC neurons. We show that Prd1 colocalizes with the clathrin adaptor protein α-Adaptin (α-Ada) and the kinesin-3 immaculate connections (Imac)/Uncoordinated-104 (Unc-104) in dendrites. Moreover, Prd1 physically associates with α-Ada and Imac, which are both critical for dendrite pruning. Prd1, α-Ada, and Imac promote dendrite pruning via the regulation of endo-lysosomal degradation of Nrg. Importantly, genetic interactions among prd1, α-adaptin, and imac indicate that they act in the same pathway to promote dendrite pruning. Our findings indicate that Prd1, α-Ada, and Imac act together to regulate discrete distribution of α-Ada/clathrin puncta, facilitate endo-lysosomal degradation, and thereby promote dendrite pruning in sensory neurons.

Background Pruning that selectively eliminates unnecessary or incorrect neurites is required for proper wiring of the mature nervous system. During Drosophila metamorphosis, dendritic arbourization sensory neurons (ddaCs) and mushroom body (MB) γ neurons can selectively prune their larval dendrites and/or axons in response to the steroid hormone ecdysone. An ecdysone-induced transcriptional cascade plays a key role in initiating neuronal pruning. However, how downstream components of ecdysone signalling are induced remains not entirely understood. Results Here, we identify that Scm, a component of Polycomb group (PcG) complexes, is required for dendrite pruning of ddaC neurons. We show that two PcG complexes, PRC1 and PRC2, are important for dendrite pruning. Interestingly, depletion of PRC1 strongly enhances ectopic expression of Abdominal B (Abd-B) and Sex combs reduced, whereas loss of PRC2 causes mild upregulation of Ultrabithorax and Abdominal A in ddaC neurons. Among these Hox genes, overexpression of Abd-B causes the most severe pruning defects, suggesting its dominant effect. Knockdown of the core PRC1 component Polyhomeotic (Ph) or Abd-B overexpression selectively downregulates Mical expression, thereby inhibiting ecdysone signalling. Finally, Ph is also required for axon pruning and Abd-B silencing in MB γ neurons, indicating a conserved function of PRC1 in two types of pruning. Conclusions This study demonstrates important roles of PcG and Hox genes in regulating ecdysone signalling and neuronal pruning in Drosophila . Moreover, our findings suggest a non-canonical and PRC2-independent role of PRC1 in Hox gene silencing during neuronal pruning.

The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development and homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we show that CRL4Mahj, an evolutionarily conserved E3 ubiquitin ligase, is essential for NSC reactivation (exit from quiescence). We demonstrate that damaged DNA-binding protein 1 (DDB1) and Cullin4, two core components of Cullin4-RING ligase (CRL4), are intrinsically required for NSC reactivation. We have identified a substrate receptor of CRL4, Mahjong (Mahj), which is necessary and sufficient for NSC reactivation. Moreover, we show that CRL4Mahj forms a protein complex with Warts (Wts/large tumor suppressor [Lats]), a kinase of the Hippo signaling pathway, and Mahj promotes the ubiquitination of Wts. Our genetic analyses further support the conclusion that CRL4Mahj triggers NSC reactivation by inhibition of Wts. Given that Cullin4B mutations cause mental retardation and cerebral malformation, similar regulatory mechanisms may be applied to the human brain.

Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning.

Background Raynaud’s syndrome (RS), also referred to as Raynaud’s phenomenon, is a vasospastic disorder causing episodic color changes in extremities upon exposure to cold or stress. These manifestations, either primary Raynaud’s phenomenon (PRP) or associated with connective tissue diseases like systemic sclerosis (SSc) as secondary Raynaud’s phenomenon (SRP), affect the quality of life. Current treatments range from calcium channel blockers to innovative surgical interventions, with evolving efficacy and safety profiles. Methods In this retrospective study, patients diagnosed with RS were selected based on complete medical records, ensuring homogeneity between groups. Surgeries involved microscopic excision of sympathetic nerve fibers and stripping of the digital artery’s adventitia. Postoperative care included antibiotics, analgesia, oral nifedipine, and heat therapies. Evaluation metrics such as the VAS pain score and RCS score were collected bi-weekly. Data analysis was conducted using SPSS 26.0, with significance set at p < 0.05. Results In total, 15 patients formed the experimental group, with five presenting fingertip soft tissue necrosis and ten showing RS symptoms. Comparative analysis of demographic data between experimental and control groups, both containing 15 participants, demonstrated no significant age and gender difference. However, the “Mean Duration of RP attack” in the experimental group was notably shorter (9.47 min ± 0.31) than the control group (19.33 min ± 1.79). The RS Severity Score also indicated milder severity for the experimental cohort (score: 8.55) compared to the control (score: 11.23). Postoperative assessments at 2, 4, and 6 weeks revealed improved VAS pain scores, RCS scores, and other measures for the experimental group, showing significant differences (p < 0.05). One distinctive case showcased a variation in the common digital nerve and artery course in an RS patient. Conclusion Our retrospective analysis on RS patients indicates that microsurgical techniques are safe and effective in the short term. As surgical practices lean towards minimally invasive methods, our data supports this shift. However, extensive, prospective studies are essential for conclusive insights.

Objective To evaluate whether 7-T susceptibility-weighted imaging (SWI) can predict glioma’s histological grade, Ki-67 labeling index (LI), isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q co-deletion, telomerase reverse transcriptase (TERT) promoter mutation, and O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status of gliomas. Materials and methods We retrospectively analyzed 7-T SWI in 60 patients with glioma. The Mann–Whitney U test compared the intratumoral susceptibility signals (ITSS) grade across molecular markers, with ITSS defined as fine linear or dot-like low signal areas on SWI. Predictive efficacy was assessed using receiver operating characteristic (ROC) analysis and multivariate logistic regression models. Path analysis evaluated the relationships between ITSS grade and molecular markers. Results Gliomas with high ITSS grade showed higher histological grade, Ki-67 LI, and TERT mutation rates compared to those with low ITSS grade, mostly being wild-type gliomas. ITSS grade predicted the histological grade, Ki-67 LI, and TERT status (area under the ROC curve = 0.769‒0.817). Multivariate logistic regression analysis identified Ki-67 LI and TERT status as independent predictors of high ITSS grade. Path analysis indicated direct effects of Ki-67 LI and TERT mutation on ITSS grade, and an indirect effect of IDH1 mutation on ITSS grade mediated through Ki-67 LI. Conclusion 7-T SWI-derived ITSS grade predicts histologic grade, Ki-67 LI, and TERT promoter mutation status in gliomas. Ki-67 LI and TERT mutation exert relatively independent effects on ITSS grade and allow reverse inference of their status from SWI, whereas IDH1 mutation influences ITSS grade indirectly via Ki-67 LI. Relevance statement This study establishes a connection between preoperative imaging and molecular glioma pathology via 7-T SWI. It helps to reveal the in vivo characteristics of pathology and promotes collaboration among radiologists, pathologists, and clinicians, which a great clinical potential. Key Points A 7-T susceptibility-weighted MRI–based intratumoral susceptibility signal (ITSS) grading system enables precise detection of glioma microbleeds and neovascularization. 7-T susceptibility-weighted MRI–derived ITSS grade noninvasively predicts histologic grade, Ki-67 labeling index, and telomerase reverse transcriptase (TERT) promoter mutation status in gliomas. Path analysis suggested that molecular markers relate to ITSS grade through distinct pathways, with Ki-67 and TERT exerting direct effects and isocitrate dehydrogenase 1 influencing ITSS grade indirectly. Graphical Abstract