Taohong Siwu decoction enhances the chemotherapeutic efficacy of doxorubicin by promoting tumor vascular normalization.

BACKGROUND: Instead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of "blood-activating and stasis-resolving" formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. PURPOSE: To study the underlying mechanisms of a classical "blood-activating and stasis-resolving" formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. STUDY DESIGN: HUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. RESULTS: Our data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206+ macrophages and increased number of CD86+ macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. CONCLUSION: This study demonstrated for the first time that TSD as a classical Chinese formula can enhance the drug efficacy and reduce the side effects of doxorubicin. These findings can support that TSD could be used as an adjuvant therapy in combination with conventional chemotherapy for the future breast cancer treatment.

The deficit in cognitive reappraisal capacity in individuals with anxiety or depressive disorders: meta-analyses of behavioral and neuroimaging studies.

BACKGROUND: The deficit in cognitive reappraisal capacity is a key factor in developing and maintaining emotional disorders such as anxiety disorders and depressive disorders. However, the results from both neuroimaging and behavioral studies are mixed. Therefore, we systematically conducted a series of meta-analyses based on behavioral and neuroimaging studies to clarify this issue. METHODS: In behavioral meta-analyses, we used three-level random-effects models to summarize the overall effect sizes based on Hedges' g. In neuroimaging meta-analyses, we used SDM-PSI to summarize the brain activation patterns. RESULTS: Behavioral meta-analyses found that individuals with anxiety disorders or depressive disorders could reduce negative reactivity through reappraisal; the reduction of negative emotions through reappraisal by individuals with anxiety disorders was similar to that by healthy individuals; the reduction by depressive disorders was lower than that of healthy individuals. Neuroimaging meta-analyses showed that individuals with anxiety disorders or depressive disorders activated regions of cognitive control during cognitive reappraisal; the activation in individuals with anxiety disorders was lower than in healthy individuals; while the activation in individuals with depressive disorders was similar to that in healthy individuals. CONCLUSION: Individuals with anxiety and depressive disorders showed dissociation in behaviour and neuroimaging patterns of cognitive reappraisal capacity deficit.

Mapping cellular interactions from spatially resolved transcriptomics data.

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently through the introduction of spatially resolved transcriptomics (SRT) technologies, especially those that achieve single-cell resolution. Nevertheless, substantial challenges remain to analyze such highly complex data properly. Here, we introduce a multiple-instance learning framework, Spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight Spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates and, most importantly, the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of Spacia for three commercialized single-cell resolution SRT technologies: MERSCOPE/Vizgen, CosMx/NanoString and Xenium/10x. Overall, Spacia represents a notable step in advancing quantitative theories of cellular communications.

Self-Assembled Nanohelixes Driven by Host-Guest Interactions and Metal Coordination.

Helical nanostructures fabricated via the self-assembly of artificial motifs have been a captivating subject because of their structural aesthetics and multiple functionalities. Herein, we report the facile construction of a self-assembled nanohelix (NH) by leveraging an achiral aggregation-induced emission (AIE) luminogen (G) and pillar[5]arene (H), driven by host-guest interactions and metal coordination. Inspired by the "sergeants and soldiers" effect and "majority rule" principle, the host-guest complexation between G and H is employed to fixate the twisted conformation of G for the generation of "contortion sites", which further induced the emergence of helicity as the 1D assemblies are formed via Ag(I) coordination and hexagonally packed into nano-sized fibers. The strategy has proved feasible in both homogeneous and heterogeneous syntheses. Along with the formation of NH, boosted luminescence and enhanced productivity of reactive oxygen species (ROS) are afforded because of the efficient restriction on G, indicating the concurrent regulation of NH's morphology and photophysical properties by supramolecular assembly. In addition, NH also exhibits the capacity for bacteria imaging and photodynamic antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).

Machine Learning-Enabled Tomographic Imaging of Chemical Short-Range Atomic Ordering.

In solids, chemical short-range order (CSRO) refers to the self-organization of atoms of certain species occupying specific crystal sites. CSRO is increasingly being envisaged as a lever to tailor the mechanical and functional properties of materials. Yet quantitative relationships between properties and the morphology, number density, and atomic configurations of CSRO domains remain elusive. Herein, it is showcased how machine learning-enhanced atom probe tomography (APT) can mine the near-atomically resolved APT data and jointly exploit the technique's high elemental sensitivity to provide a 3D quantitative analysis of CSRO in a CoCrNi medium-entropy alloy. Multiple CSRO configurations are revealed, with their formation supported by state-of-the-art Monte-Carlo simulations. Quantitative analysis of these CSROs allows establishing relationships between processing parameters and physical properties. The unambiguous characterization of CSRO will help refine strategies for designing advanced materials by manipulating atomic-scale architectures.

CO2 geological storage: A bibliometric analysis of research trends.

Geological sequestration of carbon dioxide is a critical strategy to combat global warming, playing a significant role in the reduction of greenhouse gas emissions and preservation of the global ecosystem. Over more than three decades, this domain has expanded to encompass myriad research avenues and nuanced sub-fields. Proficiency in navigating the dynamic developments and prominent challenges in this arena is imperative for promoting scholarly advancement. In this investigation, bibliometric techniques are applied to perform a comprehensive qualitative and quantitative investigation of the progression of studies on CO2 geological sequestration. The analysis incorporates a thorough review and synthesis of the accumulated literature, comprising 34,392 articles sourced from the Web of Science Core Collection. The assessment primarily scrutinizes the chronological dispersal of research outputs, geographical and institutional representation, principal journals of publication, and patterns of authorship to highlight burgeoning areas of concentrated research endeavors and prospective future research frontiers. The data reveals a pronounced surge in academic literature focusing on CO2 geological storage post-2009, which underscores the increasing value of this research sector. Investigations of CO2 geological sequestration are characterized by widespread international engagement, with notable contributions from the United States, China, and the United Kingdom substantially steering the research discourse. The core investigative themes comprise comprehensive inquiries into the physical and chemical dynamics of CO2 containment, environmental repercussions, safety assessments, evaluation methods, and technological assessments of carbon storage, along with stringent scrutiny of geological contexts for their viability and efficacy as sequestration sites.

The expression and clinical significance of ARHGAP25 in osteosarcoma based on bioinformatics analysis.

ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25's biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.

Insights into Adsorption Behavior and Mechanism of Br- onto Nickel-Aluminum Layered Double Hydroxides Intercalated with Different Inorganic Anions.

Layered double hydroxides (LDHs) have garnered significant attention from researchers in the field of adsorption due to their unique laminated structures and ion exchange properties. LDHs with various anion intercalation showed different adsorption effects on adsorbing ions, but the corresponding adsorption mechanisms are ambiguous. In this study, three types of NiAl-LDHs were synthesized, utilizing NO3-, CO32-, or Cl- as the interlayer anions. Batch tests were conducted to study their adsorption performances for Br-. Among them, the LDH with a NO3- intercalation layer exhibited the highest adsorption capacity for Br-, reaching up to 1.40 mmol g-1. The adsorption kinetics, mechanism, and renewability of these NiAl-LDHs were systematically compared. As a result, the type of Br- adsorption by all three materials was single molecular layer chemisorption. Moreover, the thermodynamic results of adsorption suggested that the adsorption of Br- was a spontaneous exothermic process. X-ray photoelectron spectroscopy, X-ray diffraction, and point of zero charge analysis collectively indicated that the adsorption of Br- by LDHs primarily occurred through interlayer ion exchange and electrostatic interactions. Structural characterizations of the adsorbents revealed that Br- entered the interlayers of the three LDHs, causing varying degrees of reduction in the interlayer spacing. Density functional theory calculations indicated that the interlayer binding energy of LDH with NO3- intercalation was the lowest, thereby making it more susceptible NO3- to be exchanged with Br-. Finally, the stability of the NiAl-LDHs was studied. The NiAl-LDHs retains a high removal efficiency of Br- even after 5 cycles of adsorption and desorption.

Blocking IL-33 decelerates cartilage degeneration in knee osteoarthritis through mice model.

INTRODUCTION: Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns and macrophages play a crucial role. However, the interaction of these mediators, the exact cause, and the treatment of knee osteoarthritis (KOA) are still unclear. Moreover, the interaction of interleukin (IL)-33, platelet-derived growth factor-BB (PDGF-BB), and matrix metalloproteinase-9 (MMP-9) with other factors in the pathogenesis of KOA has not been elaborately explored. METHOD: Therefore, in this study, we analyzed the expression of IL-33, PDGF-BB, and MMP-9 in the knee cartilage tissue of model mice, murine KOA was induced by using the destabilization of the medial meniscus (DMM) model. RESULTS: Compared with the sham operation control group, the expression levels of PDGF-BB, IL-33, and MMP-9 were increased significantly, and the pathological sections showed obvious cartilage damage. Additionally, we assessed the levels of IL-33 and MMP-9 expression in the knee joint of KOA model mice following intervention with PDGF-BB antibody, and we found that the expression level of MMP-9 was reduced following intervention with IL-33 antibody. When the effects of the three antibodies were compared in a mouse disease model, it was discovered that the IL-33 antibody could dramatically lower the relative expression level of MMP-9, resulting in the least amount of cartilage damage and improved protection. In conclusion, inhibiting IL-33 can significantly lower inflammatory factor levels in the knee joint, including IL-33 and MMP-9, and it can improve cartilage breakdown in osteoarthritis of the knee. CONCLUSION: Overall, the results indicate that IL-33 has a therapeutic function in the treatment of knee osteoarthritis and may be a novel target for treatment of the underlying causes of KOA. Additionally, PDGF-BB might be an upstream pathway of IL-33, and KOA's MMP-9 is an downstream pathway of IL-33.

Luoshi Neiyi Prescription inhibits estradiol synthesis and inflammation in endometriosis through the HIF1A/EZH2/SF-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMS) is a common gynecological disease that causes dysmenorrhea, chronic pelvic pain and infertility. Luoshi Neiyi Prescription (LSNYP), a traditional Chinese medicine (TCM) formula, is used to relieve EMS in the clinic. AIMS: This study aimed to examine the active components of LSNYP and the possible mechanism involved in its treatment of EMS. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to identify the chemical components of LSNYP. Human primary ectopic endometrial stromal cells (ecESCs) and eutopic endometrial stromal cells (euESCs) were isolated, and the expression levels of hypoxia inducible factor 1A (HIF1A), enhancer of zeste homolog 2 (EZH2) and steroidogenic factor 1 (SF-1) were detected by immunofluorescence and qPCR. Cobalt chloride (CoCl2) was utilized to construct an in vitro hypoxic environment, and lentiviruses were engineered to downregulate HIF1A and EZH2 and upregulate EZH2. Subsequently, the expression levels of HIF1A, EZH2, and SF-1 were measured using qPCR or western blotting. The binding of EZH2 to the SF-1 locus in ESCs was examined via ChIP. Furthermore, the effects of LSNYP on the HIF1A/EZH2/SF-1 pathway were evaluated both in vitro and in vivo. RESULTS: A total of 185 components were identified in LSNYP. The protein and gene expression levels of HIF1A and SF-1 were increased, whereas those of EZH2 were decreased in ecESCs. After treating euESCs with 50 µmol L-1 CoCl2 for 24 h, cell viability and estradiol (E2) production were enhanced. Hypoxia decreased EZH2 protein expression, while si-HIF1A increased it. SF-1 was increased when EZH2 was downregulated in normal and hypoxic environments, whereas the overexpression of EZH2 led to a decrease in SF-1 expression. ChIP revealed that hypoxia reduced EZH2 binding to the SF-1 locus in euESCs. In vitro, LSNYP-containing serum decreased E2 and prostaglandin E2 (PGE2) production, inhibited cell proliferation and invasion, and reduced the expression of HIF1A, SF-1, steroidogenic acute regulatory protein (StAR), and aromatase cytochrome P450 (P450arom). In vivo, LSNYP suppressed inflammation and adhesion and inhibited the HIF1A/EZH2/SF-1 pathway in endometriotic tissues. CONCLUSIONS: LSNYP may exert pharmacological effects on EMS by inhibiting E2 synthesis and inflammation through regulation of the HIF1A/EZH2/SF-1 pathway. These results suggest that LSNYP may be a promising candidate for the treatment of EMS.

Extracellular vesicles from apoptotic BMSCs ameliorate osteoporosis via transporting regenerative signals.

Rationale: Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. Methods: In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. Results: The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation in vitro and in vivo. Conclusion: Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.

Corrigendum: Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

[This corrects the article DOI: 10.3389/fimmu.2024.1302903.].

Design of PDMS/PAN composite membranes with ultra-interfacial stability via layer integration.

The interfacial interaction between the selective layer and porous substrate directly determines the separation performance and service lifetime of functional composite membranes. Till now, almost all reported polymeric selective layers are physically in contact with the substrate, which is unsatisfactory for long-term operation. Herein, we introduced a functional composite membrane with ultra-interfacial stability via layer integration between the polydimethylsiloxane selective layer and polyacrylonitrile substrate, where a facile light-triggered copolymerization achieved their covalent bonding. The critical load for the failure of the selective layer is 45.73 mN when testing the interfacial adhesion, i.e., 5.8 times higher than that before modification and significantly higher than previous reports. It also achieves superior pervaporation performance with a separation factor of 9.54 and membrane flux of 1245.6 g m-2 h-1 feeding a 1000 ppm phenol/water solution at 60 °C that is significantly higher than the same type of polymeric ones. Not limited to pervaporation, such a strategy sheds light on the design of highly stable composite membranes with different purposes, while the facile photo-trigged technique shows enormous scalability.

Integrated Information for Pathogenicity and Treatment of Spiroplasma.

Spiroplasma, belonging to the class Mollicutes, is a small, helical, motile bacterium lacking a cell wall. Its host range includes insects, plants, and aquatic crustaceans. Recently, a few human cases of Spiroplasma infection have been reported. The diseases caused by Spiroplasma have brought about serious economic losses and hindered the healthy development of agriculture. The pathogenesis of Spiroplasma involves the ability to adhere, such as through the terminal structure of Spiroplasma, colonization, and invasive enzymes. However, the exact pathogenic mechanism of Spiroplasma remains a mystery. Therefore, we systematically summarize all the information about Spiroplasma in this review article. This provides a reference for future studies on virulence factors and treatment strategies of Spiroplasma.

A high-precision oasis dataset for China from remote sensing images.

High-resolution oasis maps are imperative for understanding ecological and socio-economic development of arid regions. However, due to the late establishment and relatively niche nature of the oasis discipline, there are no high-precision datasets related to oases in the world to date. To fill this gap, detailed visual interpretation of remote sensing images on Google Earth Professional or Sentinel-2 was conducted in summer 2020, and for the first time, a high-precision dataset of China's oases (abbreviation HDCO) with a resolution of 1 meter was constructed. HDCO comprises 1,466 oases with a total area of 277,375.56 km2. The kappa coefficient for this dataset validated by the field survey was 0.8686 and the AUC value for the ROC curve was 0.935. In addition, information on the geographic coordinates, climatic conditions, major landforms, and hydrological features of each oasis was added to the attribute table of the dataset. This dataset enables researchers to quantitatively monitor location and area of oases, fosters exploration of the relationship between oases and human under climate change and urbanization.

Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration.

Successful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three-dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp-dentin complex formation. In vivo studies show that short-term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary-like structures, and improves cell survival. Long-term transplantation further confirms its capability to promote the formation of pulp-like tissues rich in blood vessels and peripheral nerve-like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.

The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.

The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

Experimental Study on the Improvement of Char Physicochemical Properties and Reactivity by Activation Process in CFB.

Solid carbon can be transformed into activated char with higher reactivity through the activation process in a circulating fluidized bed (CFB) to improve the Boudouard reaction. A new technology for reducing CO2, the activated-reduction technology, was proposed. In order to investigate the influence of relevant parameters (carbon dioxide addition, oxygen concentration, and O2/C) of the activation process on the physicochemical properties and reactivity of activated char, the experiments were carried out on a bench-scale CFB. The relationship between the parameters and the reactivity of activated char is explored. The result shows that compared with the raw coal, the pore structure of activated char is developed, the number of active sites increases, the degree of graphitization decreases, and higher reactivity is possessed. For the activation process, less of the O2/C and moderate oxygen concentration promote the increase in activated char reactivity, which is conducive to the reduction of CO2. The results of the correlation discussion show that the reactivity is difficult to be characterized by a single simple parameter. The reactive specific surface area (RSSA) obtained by multiplying the mesoporous specific surface area and I D3+D4/I all has a good effect on describing the reactivity.

Laser patterned graphene pressure sensor with adjustable sensitivity in an ultrawide response range.

Flexible pressure sensors have attracted wide attention because of their applications in wearable electronic, human-computer interface, and healthcare. However, it is still a challenge to design a pressure sensor with adjustable sensitivity in an ultrawide response range to satisfy the requirements of different application scenarios. Here, a laser patterned graphene pressure sensor (LPGPS) is proposed with adjustable sensitivity in an ultrawide response range based on the pre-stretched kirigami structure. Due to the out-of-plane deformation of the pre-stretched kirigami structure, the sensitivity can be easily tuned by simply modifying the pre-stretched level. As a result, it exhibits a maximum sensitivity of 0.243 kPa-1, an ultrawide range up to 1600 kPa, a low detection limit (6 Pa), a short response time (42 ms), and excellent stability with high pressure of 1200 kPa over 500 cycles. Benefiting from its high sensitivity and ultrawide response range, the proposed sensor can be applied to detect physiological and kinematic signals under different pressure intensities. Additionally, taking advantage of laser programmable patterning, it can be easily configured into an array to determine the pressure distribution. Therefore, LPGPS with adjustable sensitivity in an ultrawide response range has potential application in wearable electronic devices.

Advancing neural network calibration: The role of gradient decay in large-margin Softmax optimization.

This study introduces a novel hyperparameter in the Softmax function to regulate the rate of gradient decay, which is dependent on sample probability. Our theoretical and empirical analyses reveal that both model generalization and calibration are significantly influenced by the gradient decay rate, particularly as confidence probability increases. Notably, the gradient decay varies in a convex or concave manner with rising sample probability. When employing a smaller gradient decay, we observe a curriculum learning sequence. This sequence highlights hard samples only after easy samples are adequately trained, and allows well-separated samples to receive a higher gradient, effectively reducing intra-class distances. However, this approach has a drawback: small gradient decay tends to exacerbate model overconfidence, shedding light on the calibration issues prevalent in modern neural networks. In contrast, a larger gradient decay addresses these issues effectively, surpassing even models that utilize post-calibration methods. Our findings provide substantial evidence that large margin Softmax can influence the local Lipschitz constraint by manipulating the probability-dependent gradient decay rate. This research contributes a fresh perspective and understanding of the interplay between large margin Softmax, curriculum learning, and model calibration through an exploration of gradient decay rates. Additionally, we propose a novel warm-up strategy that dynamically adjusts the gradient decay for a smoother L-constraint in early training, then mitigating overconfidence in the final model.