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A bstract We propose a new strategy to look for long-lived particles (LLP) at the LHC. The LLPs are produced at one experiment, but its decay products are detected by a detector at another experiment. We use a confining Hidden Valley scenario as a benchmark. Through showering and hadronization, the multiplicity of hidden mesons can be large, and their decay products, dimuon as chosen in this study, are typically too soft to pass triggers in traditional LHC searches. We find the best acceptance is achieved if we produce LLPs at collision points at the LHCb and ALICE experiments, and use the muon chamber of ATLAS for detection. This new search is cost-efficient since it does not require a new detector to be built. Meanwhile, it can provide coverage of interesting parameter space, which is complementary to other proposed LLP searches.

In this paper, we present the design and simulation of a Stereo Crystal Electromagnetic Calorimeter (SCECal) for the Circular Electron Positron Collider (CEPC). The SCECal is based on a novel stereo crystal configuration that obtain the 3D position resolution of the calorimeter from 2D readout. We analyze the performance of the SCECal using simulations with BGO crystals and evaluate the energy and 3D positioning resolution for different types of particles. Additionally, we investigate the separation power between photons and pions using a simplified reconstruction method. The results show promising energy and position resolution as well as efficient particle separation capabilities.

We propose a new strategy to look for long-lived particles (LLP) at the LHC. The LLPs are produced at one experiment, but its decay products are detected by a detector at another experiment. We use a confining Hidden Valley scenario as a benchmark. Through showering and hadronization, the multiplicity of hidden mesons can be large, and their decay products, dimuon as chosen in this study, are typically too soft to pass triggers in traditional LHC searches. We find the best acceptance is achieved if we produce LLPs at collision points at the LHCb and ALICE experiments, and use the muon chamber of ATLAS for detection. This new search is cost-efficient since it does not require a new detector to be built. Meanwhile, it can provide coverage of interesting parameter space, which is complementary to other proposed LLP searches.

We propose a new strategy to look for long-lived particles (LLP) at the LHC. The LLPs are produced at one experiment, but its decay products are detected by a detector at another experiment. We use a confining Hidden Valley scenario as a benchmark. Through showering and hadronization, the multiplicity of hidden mesons can be large, and their decay products, dimuon as chosen in this study, are typically too soft to pass triggers in traditional LHC searches. We find the best acceptance is achieved if we produce LLPs at collision points at the LHCb and ALICE experiments, and use the muon chamber of ATLAS for detection. This new search is cost-efficient since it does not require a new detector to be built. Meanwhile, it can provide coverage of interesting parameter space, which is complementary to other proposed LLP searches.

Traditional drug development is a long and expensive process with high rates of failure. This has prompted the pharmaceutical industry to seek more efficient drug development frameworks, driving the emergence of organ-on-a-chip (OOC) based on microfluidic technologies. Unlike traditional animal experiments, OOC systems provide a more accurate simulation of human organ microenvironments and physiological responses, therefore offering a cost-effective and efficient platform for biomedical research, particularly in the development of new medicines. Additionally, OOC systems enable quick and real-time analysis, high-throughput experimentation, and automation. These advantages have shown significant promise in enhancing the drug development process. The success of an OOC system hinges on the integration of specific designs, manufacturing techniques, and biosensors to meet the need for integrated multiparameter datasets. This review focuses on the manufacturing, design, sensing systems, and applications of OOC systems, highlighting their design and sensing capabilities, as well as the technical challenges they currently face.

The antifungal activity and mechanism of rosemary essential oil against Colletotrichum gloeosporioides, the walnut anthracnose pathogen, were investigated using scanning electron microscopy (SEM), index determination and transcriptome technique. The results showed that rosemary essential oil could inhibit the growth of C. gloeosporioides with minimum inhibitory (MIC) and fungicidal (MFC) concentrations of 15.625 μL/mL and 31.25 μL/mL, respectively. Scanning electron microscopy revealed that the mycelium morphology became shriveled, twisted, and severely deformed after being treated with rosemary essential oil. The activity of chitinase, which decomposes fungal cell wall components in C. gloeosporioides, increased. The ergosterol content in the plasma membrane decreased, while the cell contents including nucleic acids, soluble protein and soluble reducing sugar were released resulting in the extracellular electrical conductivity being changed. For metabolic activity, the enzymes succinate dehydrogenase (SDH), malate dehydrogenase (MDH), ATPase and ATP decreased, whereas phosphofructokinase (PFK) increased. Transcriptome sequencing results showed that the antifungal mechanism of rosemary essential oil involves the destruction of the cell wall and membrane, inhibition of genetic material synthesis, and cell division and differentiation. The results are helpful to understand the efficacy and antifungal mechanism of rosemary essential oil against C. gloeosporioides and provide a theoretical basis for the development of rosemary essential oil as a biological control agent.

Background Alopecia affects millions of individuals globally, with hair loss becoming more common among young people.  Various traditional Chinese medicines (TCM) have been used clinically for treating alopecia, however, the effective compounds and underlying mechanism are less known. We sought to investigate the effect of Alpinetin (AP), a compound extracted from Fabaceae and Zingiberaceae herbs, in hair regeneration. Methods Animal model for hair regeneration was mimicked by depilation in C57BL/6J mice. The mice were then topically treated with 3 mg/ml AP, minoxidil as positive control (PC), or solvent ethanol as vehicle control (VC) on the dorsal skin. Skin color changes which reflected the hair growth stages were monitored and pictured, along with H&E staining and hair shaft length measurement. RNA-seq analysis combined with immunofluorescence staining and qPCR analysis were used for mechanism study. Meanwhile, Gli1 CreERT2 ; R26R tdTomato and Lgr5 EGFP−CreERT2 ; R26R tdTomato transgenic mice were used to monitor the activation and proliferation of Gli1+ and Lgr5+ HFSCs after treatment. Furthermore, the toxicity of AP was tested in keratinocytes and fibroblasts from both human and mouse skin to assess the safety. Results When compared to minoxidil-treated and vehicle-treated control mice, topical application of AP promoted anagen initiation and delayed catagen entry, resulting in a longer anagen phase and hair shaft length. Mechanistically, RNA-seq analysis combined with immunofluorescence staining of Lef1 suggested that Lgr5+ HFSCs in lower bulge were activated by AP via Wnt signaling. Other HFSCs, including K15+, Lef1+, and Gli1+ cells, were also promoted into proliferating upon AP treatment. In addition, AP inhibited cleaved caspase 3-dependent apoptosis at the late anagen stage to postpone regression of hair follicles. More importantly, AP showed no cytotoxicity in keratinocytes and fibroblasts from both human and mouse skin. Conclusion This study clarified the effect of AP in promoting hair regeneration by activating HFSCs via Wnt signaling. Our findings may contribute to the development of a new generation of pilatory that is more efficient and less cytotoxic for treating alopecia.

Purpose: Tryptophan metabolism is involved in the etiology and exacerbation of depressive disorders. Kai-Xin-San (KXS), a traditional Chinese medicine formula, has been widely used to treat depression and modulate serotonin simultaneously, but how it regulates depressive-like behavior by shifting the balance of the tryptophan-serotonin metabolism and kynurenine pathway remains vague. Patients and Methods: Ten participants with mild to moderate depression treated with KXS (KXS preparation) were analyzed in this study. Depression rating scale score and the concentration of serum tryptophan, 5-hydroxytryptophan and kynurenine was measured at baseline and the endpoint of KXS treatment. To explore the specific regulatory mechanism of KXS in tryptophan metabolism, the chronic restraint stress (CRS) was used to induce depressive-like syndrome in rats and the hippocampus level of tryptophan, 5-hydroxytryptophan, kynurenine with downstream metabolites (kynurenic acid, quinolinic acid) and key enzymes (indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase, kynurenine aminotransferase) were analyzed by liquid chromatography-electros pray ionization tandem mass spectrometry, high performance liquid chromatography and enzyme-linked immunosorbent assay respectively. Results: KXS significantly decreased depression rating scale scores and increased the serum tryptophan and kynurenine concentration in depressive patients compared to baseline. Also, it alleviated the depressive behavior in CRS rats obviously. Comparing with CRS group, KXS increased tryptophan, 5-hydroxytryptophan, kynurenine level in rat hippocampus. Furthermore, in kynurenine pathway, KXS decreased the expression of indoleamine 2,3-dioxygenase, increased kynurenic acid by upregulating the expression of kynurenine aminotransferase while decreased quinolinic acid level in hippocampus, which suggested that KXS more favored improving serotonin pathway, and neuroprotective kynurenic acid branch in the tryptophan metabolism. Conclusion: This is the first tryptophan metabolomic study of patients with depression undergoing KXS treatment. Combining these clinical results with CRS induced rat model studies, it verified that KXS achieves an excellent antidepressant effect and balances tryptophan-kynurenine metabolic pathways by regulating some key metabolic products and enzymes. Keywords: depression, amino acids, TCM, KaiXinSan

BackgroundDeafness-dystonia-optic neuronopathy (DDON) syndrome is a progressive X-linked recessive disorder characterised by deafness, dystonia, ataxia and reduced visual acuity. The causative gene deafness/dystonia protein 1 (DDP1)/translocase of the inner membrane 8A (TIMM8A) encodes a mitochondrial intermembrane space chaperon. The molecular mechanism of DDON remains unclear, and detailed information on animal models has not been reported yet.Methods and resultsWe characterized a family with DDON syndrome, in which the affected members carried a novel hemizygous variation in the DDP1 gene (NM_004085.3, c.82C>T, p.Q28X). We then generated a mouse line with the hemizygous mutation (p.I23fs49X) in the Timm8a1 gene using the clustered regularly interspaced short palindromic repeats /Cas9 technology. The deficient DDP1 protein was confirmed by western blot assay. Electron microscopic analysis of brain samples from the mutant mice indicated abnormal mitochondrial structure in several brain areas. However, Timm8a1 I23fs49X/y mutation did not affect the import of mitochondria inner member protein Tim23 and outer member protein Tom40 as well as the biogenesis of the proteins in the mitochondrial oxidative phosphorylation system and the manganese superoxide dismutase (MnSOD / SOD-2). The male mice with Timm8a1 I23fs49X/y mutant exhibited less weight gain, hearing impairment and cognitive deficit.ConclusionOur study suggests that frameshift mutation of the Timm8a1 gene in mice leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment. Taken together, we have successfully generated a mouse model bearing loss-of-function mutation in Timm8a1.

Elevated expression of the mechanosensitive ion channel PIEZO1 in response to abnormal mechanical stimuli is implicated in many diseases, including myocardial infarction (MI). However, no effective strategy is currently available to normalize PIEZO1 expression for disease management. This study investigates the therapeutic potential of mechanically adapted cardiac patches in reversing PIEZO1 elevation and treating MI. Increased mechanical stress and PIEZO1 upregulation are observed in ischemic cardiomyopathy myocardium. Using finite element analysis, elastomeric patches are designed and applied on MI rats to reduce left ventricular (LV) wall stress and mitigate LV remodeling. Molecular analysis reveals that patch treatment suppresses stress‐induced chromatin opening of the Piezo1 promoter, reversing PIEZO1 elevation and restoring heart contraction gene expression. The patch's therapeutic benefits correlate with the reversal of PIEZO1 elevation is further validated in a porcine model. Notably, constant high expression of endogenous PIEZO1 partially blocks the patch's therapeutic effects, confirming that the mechanism of patch treatment involves reversing PIEZO1 expression, in addition to providing physical support. In conclusion, cardiac patches reduce LV wall stress, preserving cardiac function and geometry by both physically supporting and biologically reversing PIEZO1 expression, highlighting the potential of medical devices in normalizing PIEZO1 expression and treating related diseases. This work identifies fine‐tuning the expression of PIEZO1 as a critical molecular mechanism underlying the treatment of myocardial infarction by mechanically adapted cardiac patches, which can support the clinical translation of cardiac patch devices.