AgentLens: Visual Analysis for Agent Behaviors in LLM-based Autonomous Systems.

Recently, Large Language Model based Autonomous System (LLMAS) has gained great popularity for its potential to simulate complicated behaviors of human societies. One of its main challenges is to present and analyze the dynamic events evolution of LLMAS. In this work, we present a visualization approach to explore the detailed statuses and agents' behavior within LLMAS. Our approach outlines a general pipeline that organizes raw execution events from LLMAS into a structured behavior model. We leverage a behavior summarization algorithm to create a hierarchical summary of these behaviors, arranged according to their sequence over time. Additionally, we design a cause trace method to mine the causal relationship between agent behaviors. We then develop AgentLens, a visual analysis system that leverages a hierarchical temporal visualization for illustrating the evolution of LLMAS, and supports users to interactively investigate details and causes of agents' behaviors. Two usage scenarios and a user study demonstrate the effectiveness and usability of our AgentLens.

Multiple topological states within a common bandgap of two non-trivial photonic crystals.

Topological photonic crystals (PCs) provide an effective method for controlling how light propagates and concentrates through their topological states. However, it remains unclear whether topological states can be obtained by combining two different two-dimensional (2D) PCs with topological non-trivial states. In this Letter, two types of 2D Penrose-square (P-S) PCs are proposed. These PCs can generate topological edge states (TESs) and topological corner states (TCSs) within the low-frequency part of the bandgap. Moreover, by combining these two non-trivial PCs, a total of two groups of TESs and four groups of TCSs can be generated in both the high-frequency and low-frequency parts of the common bandgap. To the best of our knowledge, the two proposed P-S PCs offer a new platform for investigating topological photonics and related devices, providing novel approaches and perspectives for generating topological states in 2D PCs.

Dual-band topological rainbows in Penrose-triangle photonic crystals.

Topological rainbows (TRs) possess the potential to separate and localize topological photonic states across different frequencies. However, previous works on TRs have been confined to a single-frequency band. Furthermore, the achievement of multiband TRs within a single structure is still a significant challenge. In this paper, a composed structure waveguide is designed based on Penrose-triangle photonic crystals. By adjusting the size of scatterers and introducing non-Hermitian terms, we successfully realize dual-band TRs. This achievement will not only enhance the uniformity of the electric field intensity distribution but also provide the potential to introduce a new avenue for the development of robust photonic devices dedicated to processing vast amounts of data information.

Avicularin alleviates acute liver failure by regulation of the TLR4/MyD88/NF-κB and Nrf2/HO-1/GPX4 pathways to reduce inflammation and ferroptosis.

Acute liver failure (ALF) is an inflammation-mediated hepatocyte death process associated with ferroptosis. Avicularin (AL), a Chinese herbal medicine, exerts anti-inflammatory and antioxidative effects. However, the protective effect of AL and the mechanism on ALF have not been reported. Our in vivo results suggest that AL significantly alleviated lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced hepatic pathological injury, liver enzymes, inflammatory cytokines, reactive oxygen species and iron levels and increased the antioxidant enzyme activities (malondialdehyde and glutathione). Our further in vitro experiments demonstrated that AL suppressed inflammatory response in LPS-stimulated RAW 264.7 cells via blocking the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. Moreover, AL attenuated ferroptosis in D-GalN-induced HepG2 cells by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway. Therefore, AL can alleviate inflammatory response and ferroptosis in LPS/D-GalN-induced ALF, and its protective effects are associated with blocking TLR4/MyD88/NF-κB pathway and activating Nrf2/HO-1/GPX4 pathway. Moreover, AL is a promising therapeutic option for ALF and should be clinically explored.

Inhomogeneous Microstructure Evolution of 6061 Aluminum Alloyat High Rotating Speed Submerged Friction Stir Processing.

An inhomogeneous microstructure induced by high rotating speed submerged friction stir processing (HRS-SFSP) on 6061 aluminum alloy was researched in detail.The microstructures of the aluminum alloy processing zone were characterized by electron backscattered diffraction (EBSD) and transmission electron microscope (TEM) qualitatively and quantitatively.The results show that the recrystallization proportion in the inhomogeneous structure of the processing zone is 14.3%, 37.8% and 35.9%, respectively. Different degrees of grain deformation can affect the dislocation and lead to the formation of a plastic-elastic interface. At the same time, the second-phase particles in the processing zone were inhomogeneity and relatively, which further promotes the plastic-elastic interface effect. The plastic-elastic interface can significantly improve the strength of aluminum alloy, whileat the same time, rely on recrystallized grains to provide enough plasticity. When the rotation speed was 3600 r/min, the strength and ductility of the aluminum alloy after HRS-SFSP were increased by 48.7% and 10.2% respectively compared with that of BM. In all, the plastic-elastic interface can be formed by using high rotating speed submerged friction stir processing, and the strength-ductility synergy of aluminum alloy can be realized at the plastic-elastic interface.

Multiband topological states in the Penrose-triangle photonic crystals.

The topological edge state (TES) and topological corner state (TCS) in photonic crystals (PCs) provide effective ways to manipulate the propagation of light. To improve the performance and integration of topological photonic devices, the realization of multiband topological states by PCs combined with quasi-periodic structure needs to be urgently explored. In this Letter, a Penrose-triangle (P-T) PC, which arranges the basic structural unit of a 12-fold Penrose-type photonic quasi-crystal (PQC) in a triangular lattice, is proposed. The TES and TCS at low- and high-frequency bands can be generated in the same structure, accompanied by the realization of three groups of TCSs. This will provide a new structure for the generation of TESs and TCSs in PCs, and will provide a new way to improve the performance and integration of topological photonic devices.

Higher-order topological states in two-dimensional Stampfli-Triangle photonic crystals.

In this Letter, the higher-order topological state (HOTS) and its mechanism in two-dimensional Stampfli-Triangle (2D S-T) photonic crystals (PhCs) is explored. The topological corner states (TCSs) in 2D S-T PhCs are based on two physical mechanisms: one is caused by the photonic quantum spin Hall effect (PQSHE), and the other is caused by the topological interface state. While the former leads to the spin-direction locked effect which can change the distribution of the TCSs, the latter is conducive to the emergence of multiband TCSs in the same structure due to the characteristics of plentiful photonic bandgap (PBG) and broadband in 2D S-T PhCs. These findings allow new, to the best of our knowledge, insight into the HOTS, and are significant to the future design of photonic microcavities, high-quality factor lasers, and other related integrated multiband photonic devices.

Pseudo-spin-valley coupled topological states protected by different symmetries in photonic crystals.

The quantum spin Hall effect protected by C6 symmetry [realized in the domain wall (DW) formed by a trivial-photonic crystal (TPC) and a nontrivial-PC (NPC)] and the quantum valley Hall effect protected by C3 symmetry [realized in the DW formed by two valley PCs (VPCs)] have been widely researched due to their excellent topological properties. The topological edge states (TESs) and topological corner states (TCSs) at DWs between different symmetric structures remain to be explored, which is essential for connecting waveguides with different symmetries to construct optical communication devices. In this Letter, there is (are) one TES (two TESs) for the DW1 and DW3 (DW2 and DW4) between the TPC (NPC) and two VPCs. Through simulation calculations of the Wilson-loop of the TPC and NPC and the Berry curvature distribution of VPCs, the corresponding relationship between the topological invariant and the number of TESs is obtained. Based on the TPC, NPC, and two VPCs, the waveguides are constructed to verify the realization of TESs. The parity of the gapped TESs is analyzed, and its relationship with the TCSs is obtained. Moreover, box-shaped structures are constructed to verify the appearance of TCSs. These results have a guiding significance for the research of the interaction between topological states protected by different symmetries.

Multiband topological states in non-Hermitian photonic crystals.

Novel phenomena found in non-Hermitian systems and robust edge states have attracted much attention. When non-Hermitian parameters (gain and loss) are above a critical value, the non-Hermitian photonic crystal (PC) bandgaps close, leading to a mixture of the topological edge state (TES) and topological corner state (TCS) with the bulk state. Meanwhile, new bandgaps also open, in which new TES and TCS can appear. Thus, with appropriate non-Hermitian parameters, TES can emerge in both the original bandgaps and the newly opened bandgaps. The results described here will further enrich understanding of the topological properties of non-Hermitian systems.

Fragile topology in double-site honeycomb lattice photonic crystal.

Fragile topology (FT) opens a new direction in topological photonics, but a new type of photonic crystal (PC) with FT remains to be proposed. In this Letter, the double-site honeycomb lattice (DSHL) PC is proposed by rotating the double dielectric rods (DDR) six times, forming unit cell, and then arraying the unit cells in a triangular lattice. Quantum spin Hall effect occurs by manipulating the DDR in the tangential and radial directions of the unit cell. First, the band structures of DSHL PCs with different structural parameters are calculated, and the laws of topological phase transition are analyzed statistically. Then, to prove the FT properties of two groups of topological nontrivial DSHL PCs, the Wannier-center positions of the bulk bands are calculated by the Wilson-Loop method. Finally, the topological edge states and two groups of topological corner states, which are in the same bulk-state bandgap, are realized successfully. The DSHL PC provides good platforms for both the research of topological photonics and the device design and application, which has a broad prospect.

Coupled cavity-waveguide based on topological corner state and edge state.

The topological corner state (TCS) and topological edge state (TES) have created new approaches to manipulate the propagation of light. The construction of a topological coupled cavity-waveguide (TCCW) based on the TCS and TES is worth looking forward to, due to its research prospects in realizing high-performance micro-nano integrated photonic devices. In this Letter, the TCCW is proposed in two-dimensional (2D) photonic crystal (PC), which possesses strong optical localization, high quality factor, and excellent robustness compared with the conventional coupled cavity-waveguide (CCCW). This work will pave the way toward designing high-performance logic gates, lasers, filters, and other micro-nano integrated photonics devices and expanding their applications.

The effect of intravesical hyaluronic acid therapy on urodynamic and clinical outcomes among women with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: Treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) is often delayed because of a lack of objective data during diagnosis. This study was conducted to determine the clinical validity of using urodynamic studies to investigate the effect of intravesical hyaluronic acid (HA) treatment among women with IC/BPS. MATERIALS AND METHODS: Thirty patients with IC/BPS undergoing 6-month intravesical instillation of HA were recruited. Pretreatment evaluation involved a urinalysis and urinary culture, urinary cytology, a 3-day voiding diary, and cystoscopy with hydrodistention of the bladder. Urodynamic study was performed before and after HA treatment. Symptomatic changes were assessed using a questionnaire covering lower urinary tract symptoms, the O'Leary-Sant symptom index and problem indexes (ICSI and ICPI), and the visual analog scale for pain and urgency. Patient demographics, urinary symptoms, ICSI/ICPI scores, pain and urgency scores, and urodynamic results before and after HA treatment were compared. RESULTS: Urinary frequency, nocturia, urgency, pelvic pain, bladder capacity, ICSI, and ICPI were significantly improved after HA treatment. Comparing urodynamic parameters, the volumes at first desire to void (FDV) and maximum cystometric capacity were significantly increased after HA treatment. Before HA treatment, a negative correlation existed between the ICSI and ICPI and urodynamic parameters, including maximum flow rate and bladder capacity, but there were no significant correlations after treatment. Before HA treatment, a negative correlation was discovered between nocturia and FDV. However, after HA treatment, there were no significant correlations between urinary symptoms and urodynamic parameters. CONCLUSIONS: Our results indicate that the improvement of urinary symptoms of IC/BPS after HA treatment is associated with increased FDV and maximum cystometric capacity. The value of FDV and the frequency of nocturia after treatment may become useful objective indicators for prognosis of IC/BPS.

Development of a Simple and Quick Method to Assess Base Editing in Human Cells.

Base editing is a form of genome editing that can directly convert a single base (C or A) to another base (T or G), which is of great potential in biomedical applications. The broad application of base editing is limited by its low activity and specificity, which still needs to be resolved. To address this, a simple and quick method for the determination of its activity/specificity is highly desired. Here, we developed a novel system, which could be harnessed for quick detection of editing activity and specificity of base editors (BEs) in human cells. Specifically, multiple cloning sites (MCS) were inserted into the human genome via lentivirus, and base editing targeting the MCS was performed with BEs. The base editing activities were assessed by specific restriction enzymes. The whole process only includes nucleotide-based targeting the MCS, editing, PCR, and digestion, thus, we named it NOTEPAD. This straightforward approach could be easily accessed by molecular biology laboratories. With this method, we could easily determine the BEs editing efficiency and pattern. The results revealed that BEs triggered more off-target effects in the genome than on plasmids including genomic indels (insertions and deletions). We found that ABEs (adenine base editors) had better fidelity than CBEs (cytosine base editors). Our system could be harnessed as a base editing assessment platform, which would pave the way for the development of next-generation BEs.

Protective effect of potassium 2-(l-hydroxypentyl)-benzoate on hippocampal neurons, synapses and dystrophic axons in APP/PS1 mice.

RATIONALE: As the hub of memory and space, hippocampus is very sensitive to a wide variety of injuries and is one of the earliest brain structures to develop neurodegenerative changes in AD. Previous research has showed a protective effect of potassium 2-(l-hydroxypentyl)-benzoate (PHPB) on cognitive deficits in animal models of AD. However, it is unclear whether this protective effect is associated with hippocampal alterations. OBJECTIVES: The present study was conducted to evaluate the protective effect of PHPB on hippocampal neurodegenerative changes in middle-aged APP/PS1 mice. METHODS: Ten-month-old male APP/PS1 transgenic mice and age-matched wild-type mice were randomly divided into three groups. PHPB-treated APP/PS1 group received 30 mg/kg PHPB by oral gavage once daily for 12 weeks. Wild-type group and APP/PS1 group received the same volume of water alone. Twelve weeks later, mice (13-month-old) were tested for in vivo 1H-MRS examination and then sacrificed for subsequent biochemical and pathological examinations using transmission electron microscopy, Golgi staining, immunohistochemistry, and western blotting. RESULTS: We found that PHPB treatment significantly improved the micromorphology of hippocampal neurons and subcellular organelles, ameliorated synapse loss and presynaptic axonal dystrophy, increased hippocampal dendritic spine density and dendritic complexity, enhanced the expression of hippocampal synapse-associated proteins, and improved hippocampal metabolism in middle-aged APP/PS1 mice. CONCLUSIONS: Our study showed for the first time the protective effect of PHPB on hippocampal neurons, synapses, and dystrophic axons in APP/PS1 mice, which to some extent revealed the possible mechanism for its ability to improve cognition in animal models of AD.

Hsp90ß inhibitors prevent GLT-1 degradation but have no beneficial efficacy on absence epilepsy.

The loss of glutamate transporter-1 (GLT-1) is associated with temporal lobe epilepsy (TLE). A recent study reported that Hsp90ß interacted with GLT-1 and recruited it to 20S proteasome for degradation. Therefore, inhibiting Hsp90ß may be a new strategy for treating epilepsy. So far, no studies have shown whether the inhibition of Hsp90ß had therapeutic effects on absence epilepsy. Using a model of absence epilepsy, we demonstrated that 17-allylamino-17-demethoxygeldanamycin (17AAG) and Ganetespib (STA9090) had no therapeutic effect. Although this is a negative result, it also has a meaningful exploration value for whether Hsp90 inhibitors have therapeutic effects on other epilepsy types.

Protective Effects of L-3-n-Butylphthalide Against H2O2-Induced Injury in Neural Stem Cells by Activation of PI3K/Akt and Mash1 Pathway.

It has been reported that oxidative stress could result in damage to the developing brain. L-3-n-butylphthalide (L-NBP) could inhibit neuronal cell apoptosis and has neurogenesis effect in different animal and cellular models. However, whether L-NBP could protect the process of neurogenesis in neural stem cells (NSCs) against oxidative stress injury is still unclear. Here, in the present study, we evaluated the neuroprotective effect of L-NBP in NSCs against H2O2-induced injury and the possible mechanisms. The results showed that L-NBP elevated the proliferation of NSCs by upregulating cyclin D1, and PI3K/Akt might be a possible target in this process. Subsequently, L-NBP was found to promote the migration of NSCs and N-cadherin might be involved in. NSC differentiation was measured using immunofluorescence staining and the results demonstrated that L-NBP could promote the NSCs to differentiate more into neurons. The elevation of achaete-scute homolog1 (Mash1) expression might be a key factor as attenuation of endogenous Mash1 expression by short-interfering RNA could block L-NBP-promoted neuronal differentiation. In summary, L-NBP exerts protective effects in NSCs against H2O2-induced injury by promoting the proliferation, migration and neural differentiation of NSCs, indicating that L-NBP might be a potential therapeutic agent for the neurogenesis-based treatment for some brain diseases, such as Alzheimer's disease (AD).

From stroke to neurodegenerative diseases: The multi-target neuroprotective effects of 3-n-butylphthalide and its derivatives.

Discovering effective agents to slow or stop neurodegeneration is a challenging task. Over decades, only a few drugs were approved by Food and Drug Administration (FDA) and most ended in failure. The lessons learned have switched the strategy of drug discovery from designing highly selective ligands to a network pharmacology approach. This enables many natural products like butylphthalide (NBP) once again to be regarded as a valuable source of leads for drug discovery. In this review, we first start with the neuroprotective effects of NBPs on acute ischemic stroke, and later spread to their applications in major neurodegenerative diseases. The underlying mechanisms are also discussed in order to provide a direction for further study. Hopefully, this review could bring some new insights for drug development in this struggling field.

Dl-3-n-Butylphthalide (NBP): A Promising Therapeutic Agent for Ischemic Stroke.

BACKGROUND AND OBJECTIVE: Stroke is a leading cause of morbidity and mortality in both developed and developing countries all over the world. The only drug for ischemic stroke approved by FDA is recombinant tissue plasminogen activator (rtPA). However, only 2-5% stroke patients receive rtPAs treatment due to its strict therapeutic time window. As ischemic stroke is a complex disease involving multiple mechanisms, medications with multi-targets may be more powerful compared with single-target drugs. Dl-3-n-Butylphthalide (NBP) is a synthetic compound based on l-3-n- Butylphthalide that is isolated from seeds of Apium graveolens. The racemic 3-n-butylphthalide (dl- NBP) was approved by Food and Drug Administration of China for the treatment of ischemic stroke in 2002. A number of clinical studies indicated that NBP not only improved the symptoms of ischemic stroke, but also contributed to the long-term recovery. The potential mechanisms of NBP for ischemic stroke treatment may target different pathophysiological processes, including anti-oxidant, antiinflammation, anti-apoptosis, anti-thrombosis, and protection of mitochondria et al. Conclusion: In this review, we have summarized the research progress of NBP for the treatment of ischemic stroke during the past two decades.

Activated ClC-2 Inhibits p-Akt to Repress Myelination in GDM Newborn Rats.

This study aims to investigate the effect and mechanism of type 2 voltage-gated chloride channel (ClC-2) on myelin development of newborn rats' cerebral white matter with gestational diabetes mellitus (GDM). In this study, GDM model was induced in late pregnant rat model. The alteration of ClC-2 expression in various developmental stages of cerebral white matter with/without being exposed to high glucose was analyzed using RT-PCR, active oxygen detection, TUNEL staining, Western Blot as well as immuno-histochemical staining. Our results showed that ClC-2 mRNA and protein expressions in GDM group were significantly increased in white matter of fetal rats after E18 stage, and elevated the level of TNF-α and iNOS in white matter at P0 and P3 stage of newborn rats. Meanwhile, In GDM group, reactive oxygen species (ROS) levels of the white matter at E18, P0, and P3 stage were significantly higher than control group. Furthermore, the expression level of myelin transcription factor Olig2 at P0 stage and CNPase at P3 stage were strikingly lower than that of the control group. In GDM group, ClC-2 expression in the corpus callosum (CC) and cingulate gyrus (CG) regains, and TUNEL positive cell number were increased at P0 and P3 stage. However, PDGFα positive cell number at P0 stage and CNPase expression at P3 stage were significantly decreased. Caspase-3 was also increased in those white matter regions in GDM group, but p-Akt expression was inhibited. While DIDS (a chloride channel blocker) can reverse these changes. In conclusion, ClC-2 and caspase-3 were induced by GDM, which resulted in apoptosis and myelination inhibition. The effect was caused by repressing PI3K-Akt signaling pathway. Application of ClC-2 inhibitor DIDS showed protective effects on cerebral white matter damage stimulated by high glucose concentration.

Amphetamine inhibits the N-methyl-D-aspartate receptor-mediated responses by directly interacting with the receptor/channel complex.

Amphetamine (AMPH) induces behavioral sensitization and neurotoxicity primarily by enhancing the dopamine-mediated neurotransmission. However, the involvement of the N-methyl-D-aspartate (NMDA) receptor in AMPH-induced neuropathology is also known. Recent investigation has found that high concentration of dopamine could inhibit NMDA receptor-mediated responses by blocking the NMDA receptor channel. By virtue of the structure similarity between dopamine and AMPH, we determined whether d-AMPH and its analogs, l-AMPH and methamphetamine (MAMH), could affect the NMDA receptor-mediated [3H]N-[1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP) binding in rat cortical membrane preparations and intracellular 45Ca2+ accumulation and cell death in the rat primary cortical cell cultures. AMPH concentration-dependently inhibited NMDA- and glycine-stimulated [3H]TCP binding and intracellular 45Ca2+ accumulation with two distinct potencies; a minor inhibition with high potency and a major inhibition with low potency. [3H]TCP binding suggested that the high-potency inhibition was produced by decreasing agonist-induced activation of the NMDA receptor channel. On the other hand, the low-potency inhibition was produced by competing with [3H]TCP binding in the NMDA receptor channel, like the action of noncompetitive antagonist of the NMDA receptor. However, AMPH analogs were less potent in inhibiting NMDA- and glycine-induced cultured cell death. Thus, this result indicates that AMPH could antagonize the NMDA receptor-mediated responses in vitro by two different mechanisms, probably, through directly interacting with two distinct sites on this receptor/channel complex.