Mechanisms and therapeutic potential of disulphidptosis in cancer.

SLC7A11 plays a pivotal role in tumour development by facilitating cystine import to enhance glutathione synthesis and counteract oxidative stress. Disulphidptosis, an emerging form of cell death observed in cells with high expression of SLC7A11 under glucose deprivation, is regulated through reduction-oxidation reactions and disulphide bond formation. This process leads to contraction and collapse of the F-actin cytoskeleton from the plasma membrane, ultimately resulting in cellular demise. Compared to other forms of cell death, disulphidptosis exhibits distinctive characteristics and regulatory mechanisms. This mechanism provides novel insights and innovative strategies for cancer treatment while also inspiring potential therapeutic approaches for other diseases. Our review focuses on elucidating the molecular mechanism underlying disulphidptosis and its connection with the actin cytoskeleton, identifying alternative metabolic forms of cell death, as well as offering insights into disulphidptosis-based cancer therapy. A comprehensive understanding of disulphidptosis will contribute to our knowledge about fundamental cellular homeostasis and facilitate the development of groundbreaking therapies for disease treatment.

Wafer-Scale Atomic Layer-Deposited TeOx/Te Heterostructure P-Type Thin-Film Transistors.

There is an increasing demand for p-type semiconductors with scalable growth, excellent device performance, and back-end-of-line (BEOL) compatibility. Recently, tellurium (Te) has emerged as a promising candidate due to its appealing electrical properties and potential low-temperature production. So far, nearly all of the scalable production and integration of Te with complementary metal oxide semiconductor (CMOS) technology have been based on physical vapor deposition. Here we demonstrate wafer-scale atomic layer-deposited (ALD) TeOx/Te heterostructure thin-film transistors with high uniformity and integration compatibility. The wafer-scale uniformity of the film is evidenced by spatial Raman mappings and statistical electrical analysis. Furthermore, surface accumulation-induced good ohmic contact has been observed and explained by the unique band alignment of the charge neutrality level inside the Te valence band. These results demonstrate ALD TeOx/Te as a promising p-type semiconductor for monolithic three-dimensional integration in BEOL CMOS applications incorporated with well-established n-type ALD oxide semiconductors.

ImSpiRE: image feature-aided spatial resolution enhancement method.

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure.

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models. Here, we developed a microfluidic chip for cerebral organoid culturing to reveal the neurotoxicity of low-dose constant BPS exposure on cerebral organoids. The organoids in our microfluidic system could be continuously cultured for 34 days and expressed all the essential properties of the cerebral organoids. Exposure to BPS was initiated from day 20 for concessive two weeks. The neurotoxic effects were evaluated by immunofluorescence staining and proteomics, and verified by quantitative real-time PCR. Our results indicated BPS exposure would inhibit neuron differentiation, hinder the Wnt signaling pathway, and cause alteration of signaling molecule expressions in brain regionalization. Even exposure to a low dose of BPS constantly might cause neurotoxicity during fetal brain development. Altogether, the multichannel microfluidic chip offers a general platform technique to reveal the effects of different hazardous chemicals on cerebral organoids.

[CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar â disorder].

OBJECTIVE: To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). METHODS: From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. RESULTS: Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. CONCLUSION: The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Ultrathin Ternary FeCoNi Alloy Nanoarrays in BaTiO3 Matrix for Room-Temperature Multiferroic and Hyperbolic Metamaterial.

Multifunctional vertically aligned nanocomposite (VAN) thin films exhibit considerable potential in diverse fields. Here, a BaTiO3-FeCoNi alloy (BTO-FCN) system featuring an ultrathin ternary FCN alloy nanopillar array embedded in the BTO matrix has been developed with tailorable nanopillar size and interpillar distance. The magnetic alloy nanopillars combined with a ferroelectric oxide matrix present intriguing multifunctionality and coupling properties. The room-temperature magnetic response proves the soft magnet nature of the BTO-FCN films with magnetic anisotropy has been demonstrated. Furthermore, the anisotropic nature of the dielectric-metal alloy VAN renders it an ideal candidate for hyperbolic metamaterial (HMM), and the epsilon-near-zero (ENZ) wavelength, where the real part of permittivity (ε') turns to negative, can be tailored from ∼700 nm to ∼1050 nm. Lastly, room-temperature multiferroicity has been demonstrated via interfacial coupling between the magnetic nanopillars and ferroelectric matrix.

Interferon Gamma Inducible Protein 30: from biological functions to potential therapeutic target in cancers.

Interferon Gamma Inducible Protein 30 (IFI30), also known as Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT), is predominantly found in lysosomes and the cytoplasm. As the sole enzyme identified to catalyze disulfide bond reduction in the endocytic pathway, IFI30 contributes to both major histocompatibility complex (MHC) class I-restricted antigen cross-presentation and MHC class II-restricted antigen processing by decreasing the disulfide bonds of endocytosed proteins. Remarkably, emerging research has revealed that IFI30 is involved in tumorigenesis, tumor development, and the tumor immune response. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of patients. This review provided a comprehensive overview of the research progress on IFI30 in tumor progression, cellular redox status, autophagy, tumor immune response, and drug sensitivity, with a view to providing the theoretical basis for pharmacological intervention of IFI30 in tumor therapy, particularly in immunotherapy.

Self-Assembled TiN-Metal Nanocomposites Integrated on Flexible Mica Substrates towards Flexible Devices.

The integration of nanocomposite thin films with combined multifunctionalities on flexible substrates is desired for flexible device design and applications. For example, combined plasmonic and magnetic properties could lead to unique optical switchable magnetic devices and sensors. In this work, a multiphase TiN-Au-Ni nanocomposite system with core-shell-like Au-Ni nanopillars embedded in a TiN matrix has been demonstrated on flexible mica substrates. The three-phase nanocomposite film has been compared with its single metal nanocomposite counterparts, i.e., TiN-Au and TiN-Ni. Magnetic measurement results suggest that both TiN-Au-Ni/mica and TiN-Ni/mica present room-temperature ferromagnetic property. Tunable plasmonic property has been achieved by varying the metallic component of the nanocomposite films. The cyclic bending test was performed to verify the property reliability of the flexible nanocomposite thin films upon bending. This work opens a new path for integrating complex nitride-based nanocomposite designs on mica towards multifunctional flexible nanodevice applications.

Stereoselective Synthesis of Silyl Enol Ethers with Acylsilanes and α,ß-Unsaturated Ketones.

Acylsilanes are emerging bench-stable reagents for the generation of electron-rich oxycarbenes that are difficult to access with unstable diazo compounds. Herein, we report a siloxycarbene-mediated stereoselective synthesis of silyl enol ethers through visible-light-induced intermolecular reactions between acylsilanes and α,ß-unsaturated ketones. Both the solvent and low temperature are important for the success of the reaction. This approach features atomic economics, exclusive stereocontrol, and broad substrate scope. The synthetic potential of this methodology is demonstrated by gram-scale reaction and various downstream transformations including that requiring configuration purity of the silyl enol ethers.

Investigating the mechanism of Zn cross-linking of chitin in a mycelium-based leather substitute and its performance evaluation.

Mycelium-based leather substitutes with a three-dimensional reticulated structure have attracted attention owing to the negative environmental impacts of natural and synthetic leather. This study utilised Ganoderma lucidum mycelium to prepare a mycelium-based leather substitute with zinc cross-linking (MF-Zn) and evaluated its physicochemical properties and sensory performance; the conventional Cr3+ tanning method was used as reference. Results demonstrated that Zn2+ and Cr3+ formed cross-links with the -OH and -NHOCH3 groups in the polysaccharides of chitin, while Zn2+ selectively bonded to a fraction of -NH2 groups in cystine and phenylalanine. The mycelium-based leather substitute with Zn cross-linking exhibited impressive tensile strength and tear strength of 7.0 MPa and 16.4 kN/m, respectively, while demonstrating desirable organoleptic properties. The free radical-scavenging capacity of MF-Zn was assessed, revealing a DPPH radical and hydroxyl radical scavenging rates of 39.4% and 52.7%, respectively. By successfully investigating the cross-linking mechanism of mycelial fibres with Zn2+ and obtaining the stabilised mycelium-based leather substitute, this study establishes a fundamental basis for the development of sustainable leather substitutes, meeting the requirements and facilitating significant advancements in low-carbon leather substitute production.

The rabbit model for spinal tuberculosis: An overview.

Mycobacterium tuberculosis infection has emerged as a global public health issue, predominantly manifesting as pulmonary tuberculosis. Bone and joint tuberculosis, with spinal tuberculosis accounting for approximately 50%, represents a significant form of extrapulmonary tuberculosis. Over the past years, there has been a rise in the incidence of spinal tuberculosis, and research concerning this area has gained significant attention. At present, animal models provide a means to investigate the pathogenesis, drug resistance, and novel treatment approaches for spinal tuberculosis. New Zealand rabbits, possessing a comparable anatomical structure to humans and capable of reproducing typical pathological features of human tuberculosis, are extensively employed in spinal tuberculosis research using animal models. This article comprehensively evaluates the strengths, considerations in strain selection, various modelling approaches, and practical applications of the rabbit model in studying spinal tuberculosis based on pertinent literature to guide fundamental research in this field by providing valuable insights into appropriate animal model selection.

S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/ß-catenin signaling pathway: an in vitro and in vivo study.

BACKGROUND: Intervertebral disc degeneration (IDD) is a common musculoskeletal degenerative disease, which often leads to low back pain and even disability, resulting in loss of labor ability and decreased quality of life. Although many progresses have been made in the current research, the underlying mechanism of IDD remains unclear. The apoptosis of nucleus pulposus (NP) cells (NPCs) is an important pathological mechanism in intervertebral disc degeneration (IDD). This study evaluated the relationship between S100A6 and NPCs and its underlying mechanism. METHODS: Mass spectrometry, bioinformatics, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to screen and verify hub genes for IDD in human IVD specimens with different degeneration degrees. Western blotting, immunohistochemistry (IHC), and/or immunofluorescence (IF) were used to detect the expression level of S100A6 in human NP tissues and NPCs. The apoptotic phenotype of NPCs and Wnt/ß-catenin signaling pathway were evaluated using flow cytometry, western blotting, and IF. S100A6 was overexpressed or knocked down in NPCs to determine its impact on apoptosis and Wnt/ß-catenin signaling pathway activity. Moreover, we used the XAV-939 to inhibit and SKL2001 to activate the Wnt/ß-catenin signaling pathway. The therapeutic effect of S100A6 inhibition on IDD was also evaluated. RESULTS: S100A6 expression increased in IDD. In vitro, increased S100A6 expression promoted apoptosis in interleukin (IL)-1ß-induced NPCs. In contrast, the inhibition of S100A6 expression partially alleviated the progression of annulus fibrosus (AF) puncture-induced IDD in rats. Mechanistic studies revealed that S100A6 regulates NPC apoptosis via Wnt/ß-catenin signaling pathway. CONCLUSIONS: This study showed that S100A6 expression increased during IDD and promoted NPCs apoptosis by regulating the Wnt/ß-catenin signaling pathway, suggesting that S100A6 is a promising new therapeutic target for IDD.

CT-guided ozone-mediated lumbar-renal sympathetic denervation for resistant hypertension treatment: A pilot single-arm clinical trial.

BACKGROUND: Renal sympathetic denervation (RDN) reduces blood pressure (BP). METHODS: This single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375). RESULTS: 17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by -8.6 ± 4.0 mmHg (p = 0.034) and diastolic BP (DBP) by -4.6 ± 2.1 mmHg (p = 0.032) for all participants and morning SBP by -13.2 ± 3.6 mmHg (p < 0.001), morning DBP by -6.2 ± 2.4 mmHg (p = 0.011) and daytime SBP by -4.1 ± 1.6 mmHg (p = 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation. CONCLUSIONS: CT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted.

Dynamic structural evolution of MgO-supported palladium catalysts: from metal to metal oxide nanoparticles to surface then subsurface atomically dispersed cations.

Supported noble metal catalysts, ubiquitous in chemical technology, often undergo dynamic transformations between reduced and oxidized states-which influence the metal nuclearities, oxidation states, and catalytic properties. In this investigation, we report the results of in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, and other physical characterization techniques, bolstered by density functional theory, to elucidate the structural transformations of a set of MgO-supported palladium catalysts under oxidative treatment conditions. As the calcination temperature increased, the as-synthesized supported metallic palladium nanoparticles underwent oxidation to form palladium oxides (at approximately 400 °C), which, at approximately 500 °C, were oxidatively fragmented to form mixtures of atomically dispersed palladium cations. The data indicate two distinct types of atomically dispersed species: palladium cations located at MgO steps and those embedded in the first subsurface layer of MgO. The former exhibit significantly higher (>500 times) catalytic activity for ethylene hydrogenation than the latter. The results pave the way for designing highly active and stable supported palladium hydrogenation catalysts with optimized metal utilization.

Functional Property and Regulatory Mechanism of Macrophages in Complementary and Alternative Medicine: From Bench to Clinic.

Complementary and alternative medicine (CAM) includes a wide range of treatments that are gaining acceptance among the public. It is increasingly being recognized as a viable option for treating various diseases with minimal side effects. Common avenues of this therapy include herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy, and homeopathy etc. Macrophages are highly heterogeneous cells that play multiple regulatory roles. Practices such as herbal medicine, acupuncture, physical exercise, aromatherapy and dietary therapy exert curative effects by modulating the polarization status and the secretory phenotype of macrophages directly. Furthermore, herbal medicine, acupuncture, and physical exercise influence the crosstalk between macrophages and other types of cells, including cancer cells and T cells. Mechanistically, herbal medicine and acupuncture produce curative effects in diverse diseases, including inflammatory diseases and tumors, mainly by influencing the phosphorylation of signaling proteins in macrophages. Therefore, targeting macrophages offers theoretical support for advancing the scientific understanding of this therapy and aids in identifying potential therapeutic options. Hence, in this review, we systematically summarize the different regulations of macrophages in herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy and homeopathy, and further highlight the therapeutic potential of targeting macrophages in complementary and alternative medicine.