INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling.

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments.

Sarcopenic obesity (SO) is a metabolic disorder with increasing prevalence. It is characterized by a reduction in skeletal muscle mass and strength. Resveratrol (RSV) is one of the most frequently used herbs in the treatment of skeletal muscle atrophy. However, the precise mechanism of the action of RSV in SO remains unclear. The objective of this study was to examine the pharmacological mechanism of RSV in the context of SO through the lens of network pharmacology, to validate these findings through in vivo experimentation. A list of potential RSV targets was compiled by retrieving the data from multiple databases. This list was then cross-referenced with a list of potential targets related to SO. The intersections of RSV- and SO-related targets were analyzed using Venn diagrams. To identify the core genes, a protein-protein interaction (PPI) network of the intersection targets was constructed and subsequently analyzed. Molecular docking was used to predict RSV binding to its core targets. A high-fat diet was used to induce SO in mice. These findings indicated that RSV may prevent SO by acting on 11 targets. Among these, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF) are considered core targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the anti-SO effect of RSV was predominantly linked to metabolic disease-related pathways, including those associated with nonalcoholic fatty liver disease. The anti-inflammatory effects of RSV were confirmed in vivo in an SO mouse model. This study contributes to a more comprehensive understanding of the key mechanisms of the action of RSV against SO and provides new possibilities for drug development in the pathological process of SO.

Comparison of Moses laser and Raykeen laser in patients with impacted upper ureteral stone undergoing flexible ureteroscopic holmium laser lithotripsy.

BACKGROUND: To compare the operative effect and clinical efficacy of the Moses laser mode and the Raykeen holmium laser energy platform powder mode under flexible ureteroscopic lithotripsy in patients with impacted upper ureteral stones. METHODS: From March 2022 to September 2022, 72 patients were divided into a Moses laser group and a Raykeen laser group according to surgical method, with 36 patients in each group. CT and ureteroscopy confirmed that all patients had isolated impacted upper ureteral stones. The stone volume (mm3), stone density (Hu) and severity of hydronephrosis were measured by CT. Postoperative complications were evaluated using the Clavien-Dindo score. RESULTS: There were no complications of ureteral stenosis related to the laser treatment. The operative time and lithotripsy time were lower in the Moses laser group than in the Raykeen laser group (P < 0.05). The stone-free survival rate did not differ significantly between the two groups (P = 0.722). Stone volume was found to be positively correlated with laser energy and lithotripsy time in both groups (P < 0.01). There was no significant correlation between laser energy and lithotripsy time or ureteral stone density (Hu) in the Moses laser group (P > 0.05) or the Raykeen laser group (P > 0.05). CONCLUSIONS: The contact mode of Moses technology and the powder mode of Raykeen laser lithotripsy can be used for the ablation of a single impacted upper ureteral stone. The ablation speed was related to the stone volume and the severity of polyp hyperplasia, not the stone density. We recommend the use of the powdered mode as a therapeutic measure for the treatment of impacted upper ureteral stones in flexible ureteroscopic lithotripsy.

Bio-inspired micropatterned thermochromic hydrogel for concurrent smart solar transmission and rapid visible-light stealth at all-working temperatures.

Thermochromic hydrogels exhibit a smart capacity for regulating solar spectrum transmission, enabling automatically change their transmissivity in response to the ambient temperature change. This has great importance for energy conservation purposes. Military and civilian emergency thermochromic applications require rapid visible-light stealth (VLS); however, concurrent smart solar transmission and rapid VLS is yet to be realized. Inspired by squid-skin, we propose a micropatterned thermochromic hydrogel (MTH) to realize the concurrent control of smart solar transmittance and rapid VLS at all-working temperatures. The MTH possesses two optical regulation mechanisms: optical property regulation and optical scattering, controlled by temperature and pressure, respectively. The introduced surface micropattern strategy can arbitrarily switch between normal and diffuse transmission, and the VLS response time is within 1 s compared with previous ~180 s. The MTH also has a high solar-transmission regulation range of 61%. Further, the MTH preparation method is scalable and cost-effective. This novel regulation mechanism opens a new pathway towards applications with multifunctional optical requirements.

Potential of an Amphiphilic Artificial Corneal Endothelial Layer as a Replacement Option for Damaged Corneal Endothelium.

Bullous keratopathy, a condition severely impacting vision and potentially leading to corneal blindness, necessitates corneal transplantation. However, the shortage of donor corneas and complex surgical procedures drive the exploration of tissue-engineered corneal endothelial layers. This study develops a transparent, amphiphilic, and cell-free membrane for corneal endothelial replacement. The membrane, securely attached to the posterior surface of the cornea, is created by mixing hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethylacrylate (EGDMA) in a 10:1 ratio. A 50 µL volume is used to obtain a 60 µm hydrophobic membrane on both sides, with one side treated with a polyvinylpyrrolidone (PVP) solution. The resulting membrane is transparent, foldable, biocompatible, amphiphilic, and easily handled. When exposed to 20% sulfur hexafluoride (SF6), the hydrophilic side of the membrane adheres tightly to the corneal Descemet's membrane, preventing water absorption into the corneal stroma, and thus treating bullous keratopathy. Histological test confirms its effectiveness, showing normal corneal structure and low inflammation when implanted in rabbits for up to 100 d. This study showcases the potential of this membrane as a viable option for corneal endothelial replacement, offering a novel approach to address donor tissue scarcity in corneal transplantation.

Label-Free Mapping of Multivalent Binding Pathways with Ligand-Receptor-Anchored Nanopores.

Understanding single-molecule multivalent ligand-receptor interactions is crucial for comprehending molecular recognition at biological interfaces. However, label-free identifications of these transient interactions during multistep binding processes remains challenging. Herein, we introduce a ligand-receptor-anchored nanopore that allows the protein to maintain structural flexibility and favorable orientations in native states, mapping dynamic multivalent interactions. Using a four-state Markov chain model, we clarify two concentration-dependent binding pathways for the Omicron spike protein (Omicron S) and soluble angiotensin-converting enzyme 2 (sACE2): sequential and concurrent. Real-time kinetic analysis at the single-monomeric subunit level reveals that three S1 monomers of Omicron S exhibit a consistent and robust binding affinity toward sACE2 (-13.1 ± 0.2 kcal/mol). These results highlight the enhanced infectivity of Omicron S compared to other homologous spike proteins (WT S and Delta S). Notably, the preceding binding of sACE2 to Omicron S facilitates the subsequent binding steps, which was previously obscured in bulk measurements. Our single-molecule studies resolve the controversy over the disparity between the measured spike protein binding affinity with sACE2 and the viral infectivity, offering valuable insights for drug design and therapies.

Chiral aggregates of rod-coil molecules inside nanopores as efficient nanoreactors for asymmetric synthesis.

An important subject of porous organic materials is their capacity to access enantioselectivity due to their high surface area, controllable pore size, and ease of functionalization. However, recyclability of enantio-separation is a challenge, mainly due to the complex procedures of recovery and refreshing from enantiomers. For the first time, we combined nanochannel technology and supramolecular chiral assembly to achieve efficient enantioselectivity. Fine-designed amphiphilic chiral rod-coil molecules 1-3 were immobilized to SBA-15 pore walls to form SA-M1-3 (abbreviation for amino-functionalized SBA-15 connected to molecules 1-3), which commenced chiral aggregation inside the channels. The experimental results indicated that the strong π-π stacking interaction between the rigid terphenyl groups, as well as hydrophilic-hydrophobic interaction of the amphiphiles, assisted in chiral arrangement in aqueous solution, and was accompanied by amplification of chirality. As a result, porous chiral channels exhibiting enhanced efficiency in asymmetric synthesis were manufactured, where enantioselectivity can be controlled by the initial structural design of amphiphiles that induce chiral aggregation behaviors. The chiral centers of SA-M1 and SA-M2 are located on hydrophobic and hydrophilic coils, respectively, while SA-M3 possesses both chiral coils. The SA-M materials proceeded with chiral aggregation and behaved efficiently for enantioselectivity. SA-M3, which contained the most chiral centers, showed the most optimal enantioselectivity with an enantiomeric excess (ee) value up to 71.75%, which occurred because of the strongly driven chiral aggregation of the hydrophobic and hydrophilic chiral coils. The covalent hybrid structures of the SA-M materials can be easily refreshed simply through washing, and exhibited excellent recyclability with negligible loss of efficiency. Therefore, the SA-M materials have the ability to provide sustainable and reliable application value for enantiomer separation.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Single-molecule sensing inside stereo- and regio-defined hetero-nanopores.

Heteromeric pore-forming proteins often contain recognition patterns or stereospecific selection filters. However, the construction of heteromeric pore-forming proteins for single-molecule sensing is challenging due to the uncontrollability of producing position isomers and difficulties in purification of regio-defined products. To overcome these preparation obstacles, we present an in situ strategy involving single-molecule chemical modification of a heptameric pore-forming protein to build a stereo- and regio-specific heteromeric nanopore (hetero-nanopore) with a subunit stoichiometric ratio of 3:4. The steric hindrance inherent in the homo-nanopore of K238C aerolysin directs the stereo- and regio-selective modification of maleimide derivatives. Our method utilizes real-time ionic current recording to facilitate controlled voltage manipulation for stoichiometric modification and position-based side-isomer removal. Single-molecule experiments and all-atom molecular dynamics simulations revealed that the hetero-nanopore features an asymmetric stereo- and regio-defined residue structure. The hetero-nanopore produced was characterized by mass spectrometry and single-particle cryogenic electron microscopy. In a proof-of-concept single-molecule sensing experiment, the hetero-nanopore exhibited 95% accuracy for label-free discrimination of four peptide stereoisomers with single-amino-acid structural and chiral differences in the mixtures. The customized hetero-nanopores could advance single-molecule sensing.

Micro/nanofabrication of heat management materials for energy-efficient building facades.

Advanced building facades, which include windows, walls, and roofs, hold great promise for reducing building energy consumption. In recent decades, the management of heat transfer via electromagnetic radiation between buildings and outdoor environments has emerged as a critical research field aimed at regulating solar irradiation and thermal emission properties. Rapid advancements have led to the widespread utilization of advanced micro/nanofabrication techniques. This review provides the first comprehensive summary of fabrication methods for heat management materials with potential applications in energy-efficient building facades, with a particular emphasis on recent developments in fabrication processing and material property design. These methods include coating, vapor deposition, nanolithography, printing, etching, and electrospinning. Furthermore, we present our perspectives regarding their advantages and disadvantages and our opinions on the opportunities and challenges in this field. This review is expected to expedite future research by providing information on the selection, design, improvement, and development of relevant fabrication techniques for advanced materials with energy-efficient heat management capabilities.

A network pharmacology-based study to investigate the mechanism of curcumin-regulated regenerative repair of quadriceps femoris muscle in KOA rats.

BACKGROUND: Knee osteoarthritis (KOA) is a very common musculoskeletal disorder, and patients with KOA often exhibit significant quadriceps femoris muscle atrophy. It is well established that curcumin (CUR) exerts protective effects on skeletal muscle. However, the efficacy of CUR in treating KOA-induced quadriceps femoris muscle atrophy and its underlying mechanisms remain uncertain. In this study, we employed network pharmacology to investigate the mechanism by which CUR promotes regenerative repair of the quadriceps femoris muscle in rats with KOA. METHODS: The potential targets of CUR were obtained from Swiss Target Prediction. The targets of skeletal muscle regeneration were identified from GeneCard and OMIM. A Venn diagram was generated to visualize the intersection of CUR targets and skeletal muscle regeneration targets, and the core targets were identified using STRING. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted using DAVID. Finally, the network pharmacology results were further validated by establishing a KOA rat model using the Hulth method. RESULTS: Network pharmacology analysis and molecular docking results revealed that CUR affects skeletal muscle regeneration through multiple targets and pathways. In vivo experimental results were validated by demonstrating that KOA causes atrophy and induces apoptosis in the quadriceps femoris muscle. Furthermore, CUR was shown to inhibit apoptosis in the quadriceps femoris muscle by regulating STAT3 and FOS, as well as the PI3K/AKT signaling pathway. CONCLUSIONS: Our study revealed the apoptosis-inhibiting effects of CUR and its underlying mechanisms. Consequently, CUR has the potential to improve quadriceps femoris muscle atrophy caused by KOA.

The High Resistance Loop (H-Loop) Technique for Arthroscopic Repair of Subscapularis.

The subscapularis tendon is more challenging and riskier to repair than the posterior upper rotator cuff. The knotless anchor suture in subscapularis repair simplified the repair process and had an excellent postoperative effect. We describe a new knotless anchor stitching method, the H-Loop technique. The simplicity and efficiency of the technique make it particularly suitable for small subscapular tendon tears.

Radially distributed charging time constants at an electrode-solution interface.

An electrochemically homogeneous electrode-solution interface should be understood as spatially invariant in both terms of intrinsic reactivity for the electrode side and electrical resistance mainly for the solution side. The latter remains presumably assumed in almost all cases. However, by using optical microscopy to spatially resolve the classic redox electrochemistry occurring at the whole surface of a gold macroelectrode, we discover that the electron transfer occurs always significantly sooner (by milliseconds), rather than faster in essence, at the radial coordinates closer to the electrode periphery than the very center. So is the charging process when there is no electron transfer. Based on optical measurements of the interfacial impedance, this spatially unsynchronized electron transfer is attributed to a radially non-uniform distribution of solution resistance. We accordingly manage to eliminate the heterogeneity by engineering the solution resistance distribution. The revealed spatially-dependent charging time 'constant' (to be questioned) would help paint our overall fundamental picture of electrode kinetics.

A mussel-inspired, antibacterial, antioxidant, injectable composite hydrogel for the sustain delivery of salvianolic acid B for the treatment of frozen shoulder.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Controlling DNA Fragments Translocation across Nanopores with the Synergic Use of Site-Directed Mutagenesis, pH-Dependent Charge Tuning, and Electroosmotic Flow.

Biological and solid-state nanopores are at the core of transformative techniques and nanodevices, democratizing the examination of matter and biochemical reactions at the single-molecule level, with low cost, portability, and simplicity in operation. One of the crucial hurdles in such endeavors is the fast analyte translocation, which limits characterization, and a rich number of strategies have been explored over the years to overcome this. Here, by site-directed mutagenesis on the α-hemolysin protein nanopore (α-HL), sought to replace selected amino acids with glycine, electrostatic binding sites were induced on the nanopore's vestibule and constriction region and achieved in the most favorable case a 20-fold increase in the translocation time of short single-stranded DNA (ssDNA) at neutral pH, with respect to the wild-type (WT) nanopore. We demonstrated an efficient tool of controlling the ssDNA translocation time, via the interplay between the nanopore-ssDNA surface electrostatic interactions and electroosmotic flow, all mediated by the pH-dependent ionization of amino acids lining the nanopore's translocation pathway. Our data also reveal the nonmonotonic, pH-induced alteration of ssDNA average translocation time. Unlike mildly acidic conditions (pH ∼ 4.7), at a pH ∼ 2.8 maintained symmetrically or asymmetrically across the WT α-HL, we evidenced the manifestation of a dominant electroosmotic flow, determining the speeding up of the ssDNA translocation across the nanopore by counteracting the ssDNA-nanopore attractive electrostatic interactions. We envision potential applications of the presented approach by enabling easy-to-use, real-time detection of short ssDNA sequences, without the need for complex biochemical modifications to the nanopore to mitigate the fast translocation of such sequences.

GFPBW1, a ß-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation.

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

Interprofessional delivery of Read It Again - KindergartenQ!: Classroom, educator, and child outcomes of an Australian pilot study.

PURPOSE: Australian Early Development Census (AEDC) data for the Australian Capital Territory (ACT) indicates a concerning increase in the proportion of children who are at risk or developmentally vulnerable in the domains of communication and general knowledge, and language and cognitive skills. This study investigated the effectiveness of speech-language pathologist and educator collaboration to build educator capacity to promote oral language and emergent literacy skills in preschool children. METHOD: A quasi-experimental, pre-test post-test design was used to evaluate the effectiveness of interprofessional delivery of Read It Again - KindergartenQ! on (a) children's oral language and emergent literacy outcomes, (b) educators' oral language and emergent literacy instructional practices, and (c) quality of the classroom environment. RESULT: Children demonstrated improved print knowledge and narrative skills. One of the two educators demonstrated a significant increase in their use of oral language and emergent literacy promoting strategies in their day-to-day interactions with children. No significant changes were observed in the classroom environment. CONCLUSION: Interprofessional collaboration with a coaching component is an effective method of improving children's emergent literacy skills and educator instructional practices.

Electrochemical Monitoring of Real-Time Vesicle Dynamics Induced by Tau in a Confined Nanopipette.

The microtubule-associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau's engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an electrochemical method using a synapse-mimicking nanopipette to monitor vesicle dynamics induced by tau. A model vesicle of ~30 nm is confined within a lipid-modified nanopipette orifice with a comparable diameter to mimic the synaptic lipid environment. Both tau and phosphorylated tau (p-tau) present two-state dynamic behavior in this biomimetic system, showing typical ionic current oscillation, induced by lipid-tau interaction. The results indicate that p-tau has a stronger affinity to the lipid vesicles in the confined environment, blocking the vesicle movement to a higher degree. Taken together, this method bridges a gap for sensing synaptic vesicle dynamics in a confined lipid environment, mimicking vesicle movement near the synaptic membrane. These findings contribute to understanding how different types of tau protein regulate synaptic vesicle motility and to underlying its functional and pathological behaviours in disease.

Punicalagin Ameliorates Diabetic Liver Injury by Inhibiting Pyroptosis and Promoting Autophagy via Modulation of the FoxO1/TXNIP Signaling Pathway.

Diabetic liver injury (DLI) is one of the complications of diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and the mechanism needs to be further explored. In this study, a HFD/STZ-induced diabetic mouse model is established to investigate the effect and mechanism of PU on DLI. The results show that PU intervention significantly improves liver histology and serum biochemical abnormalities in diabetic mice, significantly inhibits the expression of pyroptosis-related proteins such as NLRP3, Caspase1, IL-1ß, and GSDMD in the liver of diabetic mice, and up-regulated the expression of autophagy-related proteins. Meanwhile, PU treatment significantly increases FoxO1 protein expression and inhibits TXNIP protein expression in the liver of diabetic mice. The above results are further verified in the HepG2 cell injury model induced by high glucose. AS1842856 is a FoxO1 specific inhibitor. The intervention of AS1842856 combined with PU reverses the regulatory effects of PU on pyroptosis and autophagy in HepG2 cells. In conclusion, this study demonstrates that PU may inhibit pyroptosis and upregulate autophagy by regulating FoxO1/TXNIP signaling, thereby alleviating DLI.

[Effects of water level on soil seed bank in the floodplain wetland of Juzhang River, China]. / 水位变化对沮漳河河漫滩湿地土壤种子库的影响.

Aiming to understand the responses of soil seed bank to different water levels, we investigated vegetation and soil seed bank along a water level gradient (frequently flooded area, unflooded area) on the floodplain wetland of Juzhang River. We used the structural equation model to explore the direct and indirect effects of water level on soil seed bank, and used non-metric multidimensional scaling (NMDS) to assess the role of soil seed bank for vegetation regeneration. The results showed that the density of transient and persistent seed banks at unflooded area was 36.9% and 7.8% higher than that of frequently flooded area, respectively. Shannon index and Pielou index of seed bank and vegetation were significantly affected by water level and sampling location. Water level significantly affected the similarity between seed bank and aboveground vegetation, and the similarity of persistent seed bank with aboveground vegetation was significantly higher than that with transient seed bank. Structural equation model showed that water level had a direct effect on seed bank density, and indirect effects on density and richness of seed bank via affecting soil pH and NH4+-N content. NMDS results showed that there was no significant difference in the composition of the persistent seed bank and vegetation community in autumn under different water levels, but water level significantly changed the community composition of transient seed bank. Transient seed bank was affected by the vegetation and soil property, while persistent seed bank was determined by aboveground vegetation and water level. Although soil seed bank had low regeneration potential for the vegetation communities in floodplain wetlands, soil seed bank could not be neglected during the restoration of propagule diversity after disturbance in wetlands. Persistent seed bank would be an importance source of diversity of propagules for floodplain wetlands restoration following disturbance.