Quasimaps to quivers with potentials

This paper is concerned with a non-compact GIT quotient of a vector space, in the presence of an abelian group action and an equivariant regular function (potential) on the quotient. We define virtual counts of quasimaps from prestable curves to the critical locus of the potential, and prove a gluing formula in the formalism of cohomological field theories. The main examples studied in this paper is when the above setting arises from quivers with potentials, where the above construction gives quantum correction to the equivariant Chow homology of the critical locus. Following similar ideas as in quasimaps to Nakajima quiver varieties studied by the Okounkov school, we analyse vertex functions in several examples, including Hilbert schemes of points on $\mathbb{C}^3$, moduli spaces of perverse coherent systems on the resolved conifold, and a quiver which defines higher $\mathfrak{sl}_2$-spin chains. Bethe equations are calculated in these cases. The construction in the present paper is based on the theory of gauged linear sigma models as well as shifted symplectic geometry of Pantev, To\"en, Vaquie and Vezzosi, and uses the virtual pullback formalism of symmetric obstruction theory of Park, which arises from the recent development of Donaldson-Thomas theory of Calabi-Yau 4-folds.Comment: 87 page

Learning and Evaluating Human Preferences for Conversational Head Generation

A reliable and comprehensive evaluation metric that aligns with manual preference assessments is crucial for conversational head video synthesis method development. Existing quantitative evaluations often fail to capture the full complexity of human preference, as they only consider limited evaluation dimensions. Qualitative evaluations and user studies offer a solution but are time-consuming and labor-intensive. This limitation hinders the advancement of conversational head generation algorithms and systems. In this paper, we propose a novel learning-based evaluation metric named Preference Score (PS) for fitting human preference according to the quantitative evaluations across different dimensions. PS can serve as a quantitative evaluation without the need for human annotation. Experimental results validate the superiority of Preference Score in aligning with human perception, and also demonstrates robustness and generalizability to unseen data, making it a valuable tool for advancing conversation head generation. We expect this metric could facilitate new advances in conversational head generation

Pathogenic Mutations Differentially Regulate Cell-to-Cell Transmission of α-Synuclein

Recent studies suggest that the cell-to-cell spread of pathological α-synuclein (α-syn) plays important roles in the development of Parkinson’s disease (PD). PD patients who carry α-syn gene mutations often have an earlier onset and more severe clinical symptoms and pathology than sporadic PD cases who carry the wild-type (WT) α-syn gene. However, the molecular mechanism by which α-syn gene mutations promote PD remains unclear. Here, we hypothesized that pathogenic mutations facilitate the intercellular transfer and cytotoxicity of α-syn, favoring an early disease onset and faster progression. We investigated the effects of eight known pathogenic mutations in human α-syn (A18T, A29S, A30P, E46K, H50Q, G51D, A53E, and A53T) on its pathological transmission in terms of secretion, aggregation, intracellular level, cytotoxicity, seeding, and induction of neuroinflammation in SH-SY5Y neuroblastoma cells, cultured rat neurons, and microglia, and the rat substantia nigra pars compacta. We found that 2 of the 8 mutations (H50Q and A53T) significantly increased α-syn secretion while 6 mutations (A18T, A29S, A30P, G51D, A53E, and E46K) tended to enhance it. In vitroα-syn aggregation experiments showed that H50Q promoted while G51D delayed aggregation most strongly. Interestingly, 3 mutations (E46K, H50Q, and G51D) greatly increased the intracellular α-syn level when cultured cells were treated with preformed α-syn fibrils (PFFs) compared with the WT, while the other 5 had no effect. We also demonstrated that H50Q, G51D, and A53T PFFs, but not E46K PFFs, efficiently seeded in vivo and acutely induced neuroinflammation in rat substantia nigra pars compacta. Our data indicate that pathogenic mutations augment the prion-like spread of α-syn at different steps and blockade of this pathogenic propagation may serve as a promising therapeutic intervention for PD

Application experience of artificial perfusion combined with interception basket in ureteral calculi lithotripsy

Objective To evaluate clinical efficacy of artificial perfusion combined with interception basket in ureteral calculi lithotripsy. Methods Clinical data of 151 patients with ureteral calculi who underwent surgical treatment were retrospectively analyzed. They were divided into the observation group（artificial perfusion combined with interception basket）and control group（conventional perfusion pump）. The operation time，intraoperative blood loss，proportion of stone escape，stone re-intervention and complications were observed in two groups. Results There were no significant differences in operation time，intraoperative blood loss and incidence of complications between two groups（all P > 0.05）. The proportion of stone escape and stone re-intervention in the observation group were significantly lower than those in the control group，and the differences were statistically significant（both P < 0.05）. Conclusion Artificial low-pressure perfusion combined with interception basket in ureteral stone lithotripsy can reduce the proportion of stone escape and residual stone re-intervention and improve the stone clearance efficiency

The Stimulative Effect of Yangjing Capsule on Testosterone Synthesis through Nur77 Pathway in Leydig Cells

Yangjing Capsule (YC), an innovative Chinese medicine based on traditional prescription, promotes testosterone synthesis by upregulating the expression of steroidogenic enzymes. Nur77 as a nuclear receptor is known to regulate the expression of many steroid synthetases. This study aimed to explore the potential mechanisms by which YC regulates testosterone synthesis in Leydig cells. Real-time PCR and Western blot analysis were employed to assess the expressions of steroidogenic enzymes and Nur77 after treating MLTC-1 cells with YC. The luciferase reporter gene assay was performed to detect the activity of Nur77 gene promoter. Also, the expressions of steroid synthases were detected after Nur77 gene was knocked down. YC significantly stimulated Nur77 production and upregulated StAR and HSD3B expression, and this agrees with the activity of Nur77 gene promoter that was significantly enhanced by YC. Interestingly, knockdown of Nur77 blocked the above YC’s effects and consequently inhibited testosterone synthesis in MLTC-1 cells. YC promotes StAR and HSD3B expression and upregulates testosterone synthesis in Leydig cells, which is mediated by Nur77 pathway

A Small Molecule Antagonist of SMN Disrupts the Interaction Between SMN and RNAP II

Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target engagement assays support that compound 1 specifically recognizes SMN in a cellular context and prevents the interaction of SMN with the R1810me2s of RNA polymerase II subunit POLR2A, resulting in transcription termination and R-loop accumulation mimicking SMN depletion. Thus, in addition to the antisense, RNAi and CRISPR/Cas9 techniques, potent SMN antagonists could be used as an efficient tool to understand the biological functions of SMN