Additive manufacturing of degradable metallic scaffolds for material-structure-driven diabetic maxillofacial bone regeneration.

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn-Mg-Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Geomagnetic Disturbances and Pulse Amplitude Anomalies Preceding M > 6 Earthquakes from 2021 to 2022 in Sichuan-Yunnan, China.

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Engineering of the start condensation domain with improved N-decanoyl catalytic activity for daptomycin biosynthesis.

Daptomycin, a lipopeptide comprising an N-decanoyl fatty acyl chain and a peptide core, is used clinically as an antimicrobial agent. The start condensation domain (dptC1) is an enzyme that catalyzes the lipoinitiation step of the daptomycin synthesis. In this study, we integrated enzymology, protein engineering, and computer simulation to study the substrate selectivity of the start condensation domain (dptC1) and to screen mutants with improved activity for decanoyl loading. Through molecular docking and computer simulation, the fatty acyl substrate channel and the protein-protein interaction interface of dptC1 are analyzed. Key residues at the protein-protein interface between dptC1 and the acyl carrier were mutated, and a single-point mutant showed more than three-folds improved catalytic efficiency of the target n-decanoyl substrate in comparing with the wild type. Moreover, molecular dynamics simulations suggested that mutants with increased catalytic activity may correlated with a more "open" and contracted substrate binding channel. Our work provides a new perspective for the elucidation of lipopeptide natural products biosynthesis, and also provides new resources to enrich its diversity and optimize the production of important components.

Value of orthogonal axial MR images in preoperative T staging of gastric cancer.

PURPOSE: To assess the value of orthogonal axial images (OAI) of MRI in gastric cancer T staging. METHODS: This retrospective study enrolled 133 patients (median age, 63 [range, 24-85] years) with gastric adenocarcinoma who underwent both CT and MRI followed by surgery. MRI lacking or incorporating OAI and CT images were evaluated, respectively. Diagnostic performance (accuracy, sensitivity, and specificity) for each T stage, overall diagnostic accuracy and rates of over- and understaging were quantified employing pathological T stage as a reference standard. The McNemar's test was performed to compare the overall accuracy. RESULTS: Among patients with pT1-pT4 disease, MRI with OAI (accuracy: 88.7-94.7%, sensitivity: 66.7-93.0%, specificity: 91.5-100.0%) exhibited superior diagnostic performance compared to MRI without OAI (accuracy: 81.2-88.7%, sensitivity: 46.2-83.1%, specificity: 85.5-99.1%) and CT (accuracy: 88.0-92.5%, sensitivity: 53.3-90.1%, specificity: 88.7-98.1%). The overall accuracy of MRI with OAI was significantly higher (83.5%) than that of MRI without OAI (67.7%) (p < .001). However, there was no significant difference in the overall accuracy of MRI with OAI and CT (78.9%) (p = .35). The over- and understaging rates of MRI with OAI (12.0, 4.5%) were lower than those of MRI without OAI (21.8, 10.5%) and CT (12.8, 8.3%). CONCLUSION: OAI play a pivotal role in the T staging of gastric cancer. MRI incorporating OAI demonstrated commendable performance for gastric cancer T-staging, with a slight tendency toward its superiority over CT.

Transforming Adolescent Smiles: Correcting Skeletal Mandibular Retrusion and Bimaxillary Protrusion with Clear Aligners.

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients' facial aesthetics and mental health. The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques, combined with mini-implant screws, to retract the anterior teeth and improve facial protrusion. In recent years, an invisible orthodontic technique, without brackets, has become increasingly popular. However, while an invisible aligner has been used in some cases with reasonable results, there remain significant challenges in achieving a perfect outcome. This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia. Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent's teeth and jawbone, we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth, while utilizing the patient's jawbone growth potential to promote rapid development of the mandible, accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia. The patient's facial aesthetics, especially the lateral morphology, have been greatly improved, and various aesthetic indicators have also shown significant changes, and to the patient's great benefit, invasive mini-implant screws were not used during the treatment. This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients. Furthermore, comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions, providing clinical guidance for orthodontists.

Design, synthesis and biological evaluation of quinazoline and pyrrolo[3,2-d]pyrimidine derivatives as TLR7 agonists for antiviral agents.

Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of -4.45 kcal mol-1. These results suggested that these compounds might be potential antiviral agents.

High resolution acoustic sensing based on microcavity optomechanical oscillator.

In this paper, a simple sensing method based on a silicon oxide microcavity optomechanical oscillator (OMO) is proposed and demonstrated for the detection of acoustic signals. Firstly, the resonance damping was reduced by improving the optical quality factor (Qo) and increasing the sphere-to-neck ratio. After optimizing the process, a microsphere OMO was fabricated, which has an ultra-high mechanical quality factor (6.8 × 106) and greater sphere-to-neck ratio (∼11:1), based on which ultra-narrow linewidth phonon laser (∼1 Hz) is constructed. Secondly, by changing the refractive index of the coupling interval, the low-frequency acoustic pressure signal is efficiently coupled into the microcavity OMO to construct a high-resolution acoustic sensor. This sensing mechanism can not only measure the acoustic pressure, but also use the sideband signal in the modulation mechanism to measure the frequency of acoustic signals (15 Hz∼16 kHz), the sensitivity is 10.3 kHz/Pa, the minimum detectable pressure is 1.1 mPa, and noise-limited minimum detectable pressure is 28.8 µPa/Hz1/2. It is the highest detection resolution compared with the same type of low-frequency acoustic signal detection currently reported. This OMO-based acoustic sensing detection method opens up a new path for future miniaturized, ultra-high-precision, and cost-effective acoustic sensing.

Structural View of Cryo-Electron Microscopy-Determined ATP-Binding Cassette Transporters in Human Multidrug Resistance.

ATP-binding cassette (ABC) transporters, acting as cellular "pumps," facilitate solute translocation through membranes via ATP hydrolysis. Their overexpression is closely tied to multidrug resistance (MDR), a major obstacle in chemotherapy and neurological disorder treatment, hampering drug accumulation and delivery. Extensive research has delved into the intricate interplay between ABC transporter structure, function, and potential inhibition for MDR reversal. Cryo-electron microscopy has been instrumental in unveiling structural details of various MDR-causing ABC transporters, encompassing ABCB1, ABCC1, and ABCG2, as well as the recently revealed ABCC3 and ABCC4 structures. The newly obtained structural insight has deepened our understanding of substrate and drug binding, translocation mechanisms, and inhibitor interactions. Given the growing body of structural information available for human MDR transporters and their associated mechanisms, we believe it is timely to compile a comprehensive review of these transporters and compare their functional mechanisms in the context of multidrug resistance. Therefore, this review primarily focuses on the structural aspects of clinically significant human ABC transporters linked to MDR, with the aim of providing valuable insights to enhance the effectiveness of MDR reversal strategies in clinical therapies.

Salinity stress results in ammonium and nitrite accumulation during the elemental sulfur-driven autotrophic denitrification process.

In this study, we investigated the effects of salinity on elemental sulfur-driven autotrophic denitrification (SAD) efficiency, and microbial communities. The results revealed that when the salinity was ≤6 g/L, the nitrate removal efficiency in SAD increased with the increasing salinity reaching 95.53% at 6 g/L salinity. Above this salt concentration, the performance of SAD gradually decreased, and the nitrate removal efficiency decreased to 33.63% at 25 g/L salinity. Approximately 5 mg/L of the hazardous nitrite was detectable at 15 g/L salinity, but decreased at 25 g/L salinity, accompanied by the generation of ammonium. When the salinity was ≥15 g/L, the abundance of the salt-tolerant microorganisms, Thiobacillus and Sulfurimonas, increased, while that of other microbial species decreased. This study provides support for the practical application of elemental sulfur-driven autotrophic denitrification in saline nitrate wastewater.

Visitor preferences in rural gastronomic tourism environment and the related design implications.

Since COVID-19, people have suffered tremendous impacts in all aspects of their lives and work, with subtle changes in their environment preferences. The rural areas, with their natural green space, low density, and leisurely habitat, have played an important role after the pandemic and are widely favored by people. Research on rural environments after COVID-19 has received much attention. In the wake of the pandemic, people's needs for the environment have changed not only in terms of physical space, but also in terms of psychological needs. To address the issue of adaptability and resiliency of the future tourism development of the rural areas, this study takes the real subjective feelings of rural visitors as the evaluation standard, and takes the rural gastronomic tourism environment as the research object. We analyzed a sample of 14,373 images and 324,676 comments in Chinese posted by 3484 visitors on social media to explore whether and how people's preferences for rural environments have changed since the pandemic. Findings revealed significant differences in preference for the rural gastronomic tourism environment factors before and after the pandemic. There is variability in environment preferences depending on different gender, environment flexibility and the region. From the perspective of the rural gastronomic tourism environment, the research results provide suggestions for rural planning and rural tourism sustainability, and provide feasible paths for sustainable development and conservation of rural landscapes oriented to human needs, to enhance the resilience and sustainability of rural environments in the future.

Atomic Zincophilic Sites Regulating Microspace Electric Fields for Dendrite-Free Zinc Anode.

Aqueous Zn metal batteries are promising candidates for large-scale energy storage due to their intrinsic advantages. However, Zn tends to deposit irregularly and forms dendrites driven by the uneven space electric field distribution near the Zn-electrolyte interphase. Herein it is demonstrated that trace addition of Co single atom anchored carbon (denoted as CoSA/C) in the electrolyte regulates the microspace electric field at the Zn-electrolyte interphase and unifies Zn deposition. Through preferential adsorption of CoSA/C on the Zn surface, the atomically dispersed Co-N3 with strong charge polarization effect can redistribute the local space electric field and regulate ion flux. Moreover, the dynamic adsorption/desorption of CoSA/C upon plating/stripping offers sustainable long-term regulation. Therefore, Zn||Zn symmetric cells with CoSA/C electrolyte additive deliver stable cycling up to 1600 h (corresponding to a cumulative plated capacity of 8 Ah cm-2 ) at a high current density of 10 mA cm-2 , demonstrating the sustainable feature of microspace electric field regulation at high current density and capacity.

Wireless Electric Cues Mediate Autologous DPSC-Loaded Conductive Hydrogel Microspheres to Engineer the Immuno-Angiogenic Niche for Homologous Maxillofacial Bone Regeneration.

Stem cell therapy serves as an effective treatment for bone regeneration. Nevertheless, stem cells from bone marrow and peripheral blood are still lacking homologous properties. Dental pulp stem cells (DPSCs) are derived from neural crest, in coincidence with maxillofacial tissues, thus attracting great interest in in situ maxillofacial regenerative medicine. However, insufficient number and heterogenous alteration of seed cells retard further exploration of DPSC-based tissue engineering. Electric stimulation has recently attracted great interest in tissue regeneration. In this study, a novel DPSC-loaded conductive hydrogel microspheres integrated with wireless electric generator is fabricated. Application of exogenous electric cues can promote stemness maintaining and heterogeneity suppression for unpredictable differentiation of encapsulated DPSCs. Further investigations observe that electric signal fine-tunes regenerative niche by improvement on DPSC-mediated paracrine pattern, evidenced by enhanced angiogenic behavior and upregulated anti-inflammatory macrophage polarization. By wireless electric stimulation on implanted conductive hydrogel microspheres, loaded DPSCs facilitates the construction of immuno-angiogenic niche at early stage of tissue repair, and further contributes to advanced autologous mandibular bone defect regeneration. This novel strategy of DPSC-based tissue engineering exhibits promising translational and therapeutic potential for autologous maxillofacial tissue regeneration.

Novel conjugated microporous polymers for efficient tetracycline adsorption: insights from theoretical investigations.

This paper presents a detailed theoretical understanding of the noncovalent interactions between antibiotics tetracycline and conjugated microporous polymer (CMP), which is important to understand the recent experimental finding of efficient removal of antibiotics by CMP materials. We show that the co-work of π-π and H-π interactions determines the final equilibrium structures, when a tetracycline molecule spontaneously adsorbs to the surface or within the pores of the CMP network at physisorption distances. The binding energies for tetracycline/CMP systems are calculated to be -0.31 âˆ¼ -1.15 eV, demonstrating the reliability of the adsorption. The electronic structures of CMP nanostructures remain basically undamaged upon the tetracycline adsorption. The replacement of benzothiadiazole unit with S and N heteroatoms to the phenyl moiety in the linker effectively enhanced the molecular polarity of CMP molecule and increases the interaction area between tetracycline and CMP network, consequently enhancing the average binding energies notably. Our calculations provide useful theoretical guidance for design of novel carbon-based porous adsorbents with good adsorption performance to remove residual tetracycline and other antibiotics in water.

Comprehensive Analysis of the Expression and Prognosis for Lipid Metabolism-Related Genes in Hepatocellular Carcinoma.

Hao DingBackground This study aimed to screen potential key genes associated with lipid metabolism and to evaluate their expressions and prognosis values in hepatocellular carcinoma (HCC). Methods Data sets GSE6764, GSE14520, and GSE112790 were used to identify the common differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed by STRING database. Hub genes in PPI network were identified and subjected to functional enrichment analysis to screen lipid metabolism-related genes. The expressions of selected genes and their associations with prognosis were analyzed using UALCAN, The Human Protein Atlas, and Kaplan-Meier plotter databases. The transcriptional factor (TF)-gene regulatory network was constructed using NetworkAnalyst. Results A total of 331 common DEGs including 106 upregulated and 225 downregulated genes were identified. PPI network analysis showed that 76 genes with high degrees were identified as hub genes, among which 14 genes were lipid metabolism-related genes. PON1, CYP2C9, and SPP1 were found to be the independent prognostic markers. Key TFs with close interactions with these prognostic genes, including HINFP, SRF, YY1, and NR3C1, were identified from the TF-gene regulatory network. Conclusion This study presented evidence for the prognostic capabilities of lipid metabolism-related genes in HCC, and newly identified HINFP and NR3C1 as potential biomarkers for HCC.

Clinical Analysis of 3D-Fluid Attenuated Inversion Recovery and T1volume interpolated body examination Sequences on Delayed Gadolinium-Enhanced Scanning in Ramsay Hunt Syndrome.

BACKGROUND: Through the clinical analysis of 4 clinically confirmed cases of delayed gadolinium enhancement of Ramsay Hunt syndrome 3D-Fluid Attenated Inversion Recovery'and 'T1volume interpolated body examination (3D-FLAIR and T1VIBE) sequences, the more suitable sequences and pathologically damaged tissue sites of deep tissues of Ramsay Hunt syndrome by magnetic resonance imaging gadolinium enhancement were preliminarily explored. METHODS: From October 2020 to March 2021, 4 clinically confirmed patients with Ramsay Hunt syndrome, 2 males and 2 females, aged 27-63, were continuously collected in the hospital otology clinic. Siemens Avento 1.5T magnetic resonance imaging 3D-FLAIR and T1VIBE sequencedelayed gadolinium enhancement scans and serological laboratory tests were performed, respectively, and corresponding antiviral and antiinflammatory therapy was given. RESULTS: The magnetic resonance imaging gadolinium enhancement of 4 cases of Ramsay Hunt syndrome was as follows: 3D-FLAIR sequence delay of 4.5 hours scanning 4 patients labyrinthine and/or middle ear signal was enhanced at the same time as the healthy side; T1VIBE sequence scanning disease in 3 cases of vestibular nerve development was enhanced than the healthy side, 2 cases of facial nerve development was enhanced than the healthy side, and 2 cases of cochlear nerve development was enhanced than the healthy side. All 4 patients were cured with related treatment. CONCLUSION: Through the comparison of 3D-FAIR and T1VIBE sequence of 4.5 hours delay before intravenous gadolinium injection and 4.5 hours delay after intravenous gadolinium injection in 4 patients with Ramsay Hunt syndrome, it was found that (i) 3D-FLAIR sequence delay of 4.5 hours scan was more likely to show whether the inner ear labyrinth barrier permeability increased and (ii) Ramsay Hunt syndrome deep ear tissue damage can be manifested as labyrinthitis, vestibular cochlear neuritis, facial neuritis, and otitis media.

Zwitterionic silver nanoparticle based antibacterial eye drops for efficient therapy of bacterial keratitis.

Inefficient biofilm clearance and the risk of drug resistance pose significant challenges for antibiotic eye drops in the treatment of bacterial keratitis (BK). Recently, silver nanoparticles (AgNPs) have emerged as promising alternatives to antibiotics due to their potent antibacterial activity and minimal drug resistance. However, concerns regarding the potential biotoxicity of aggregated AgNPs in tissues have limited their practical application. In this study, polyzwitterion-functionalized AgNPs with excellent dispersion stability in the ocular physiological environment were chosen to prepare antibacterial eye drops. Zwitterionic AgNPs were synthesized using a copolymer, poly(sulfobetaine methacrylate-co-dopamine methacrylamide) (PSBDA), as a stabilizer and a reducing agent. The resulting antibacterial eye drops, named ZP@Ag-drops, demonstrated outstanding biocompatibility in in vitro cytotoxicity tests and in vivo rabbit eye instillation experiments, attributed to the zwitterionic PSBDA surface. Furthermore, the ZP@Ag-drops exhibited strong antibacterial activity against multiple pathogenic bacteria, particularly in penetrating and eradicating biofilms, due to the synergistic bactericidal effect of the released Ag+ and reactive oxygen species (ROS). Importantly, in vivo BK rabbit models showed that the ZP@Ag-drops effectively inhibited corneal infection and prevented ocular tissue damage, surpassing the therapeutic effect of commercial levofloxacin eye drops (LEV-drops). Overall, this study presents a promising alternative option for the effective treatment of BK using antibacterial eye drops.

[Silencing of SMAD family member 3 promotes M2 polarization of macrophages and the expression of SMAD7 in rheumatoid arthritis].

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor ß1 (TGF-ß1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-ß1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in TranswellTM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-ß1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-ß1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. TranswellTM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-ß1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.

Geranylgeranylacetone Ameliorates Skin Inflammation by Regulating and Inducing Thioredoxin via the Thioredoxin Redox System.

Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-α, IL-1ß, GM-CSF, and 8-OHdG. GGA's cytoprotective effect was stronger orally than topically in mice. In vitro studies also showed that GGA suppressed the expression of NLRP3, TNF-α, IL-1ß, and GM-CSF and scavenged ROS in PAM212 cells after phorbol myristate acetate stimulation. Moreover, GGA induced endogenous TRX production and Nrf2 nuclear translocation in PAM212 cells (dependent on the presence of ROS) and activated the PI3K-Akt signaling pathway. GGA significantly downregulated thioredoxin-interacting protein (TXNIP) levels in PAM212 cells treated with or without Nrf2 siRNA. After knocking down Nrf2 in PAM212 cells, the effect of GGA on TRX induction was significantly inhibited. This suggests that GGA suppress ICD by inducing endogenous TRX, which may be regulated by PI3K/Akt/Nrf2 mediation of the TRX redox system.

Present-Day Tectonic Stress Evolution in Southern Yunnan Based on Focal Mechanisms.

Tectonic extrusion bypassing the eastern Himalayan syntaxis results in a significant increase in regional stress instability and the associated frequent occurrence of earthquakes in southern Yunnan, China. However, the stress field, and the relationship between the focal mechanism of earthquakes and stress evolution in southern Yunnan, remain enigmatic. In this paper, using a modified grid point test method, we calculated the focal mechanism of ML ≥ 2.5 earthquakes in southern Yunnan (22-25° N, 100-104° E) from January 2009 to June 2023. Utilizing the solutions of historical earthquake focal mechanisms, we obtained the present-day regional tectonic stress field in southern Yunnan via inversion. The results indicate complex and diverse seismic focal mechanisms, and the main types of earthquakes are strike-slip events, followed by normal fault and reverse fault events. The orientations of the maximum and minimum principal stress axes rotate in a clockwise direction from northeast to southwest. The internal stress orientation distribution of the rhombic Sichuan-Yunnan block in the study area is consistent, and the block boundary zone is the site where stress deflection occurs, and the regional tectonic stress field is influenced by the interaction among different blocks. The distribution of R-value in the Lamping-Simao block gradually increases from north to south, indicating that the compressive stress required for material transport becomes relatively small. Combined with the geological and tectonic background of the study area, our results suggest that the speed of block movement gradually decreases from north to south; the distribution of R-value in the South China block is significantly smaller than that of the interior of the Sichuan-Yunnan rhombus, and the proportion of compressive stresses is larger, indicating a stronger extrusion in this region, which may be related to the fact that the Sichuan-Yunnan rhombus is strongly resisted by the South China block in the east.