MXene-Fiber Composite Membranes for Permeable and Biocompatible Skin-Interfaced Iontronic Mechanosensing.

Artificial ionic sensory systems, bridging the divide between biological systems and electronics, mimic human skin functions but face critical challenges with biocompatibility, comfort, signal stability, and simplifying packaging. Here, we present a simple and permeable skin-interfaced iontronic mechanosensing (SIIM) architecture that integrates human skin as natural ionic material and hierarchically porous MXene-fiber composite membranes as sensing electrodes. The SIIM system eliminates complex ionic material design and multilayer matrix, exhibiting ultrahigh pressure sensitivities (5.4 kPa-1, <75 Pa), a low detection limit (6 Pa), excellent output stability along with high permeability to minimize the impact of sweating on sensing. The noncytotoxic nature of SIIM electrodes ensures excellent biocompatibility (>97% cell coincubational viability), facilitating long-term wearability and high biosafety. Furthermore, the scalable SIIM configuration integrated with matrix smart gloves, effectively monitors human physical movements. This SIIM-based sensor with marked sensing capabilities, structural simplicity, and scalability, holds promising potential in diverse wearable applications.

MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice.

The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin-induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor-ß1 (TGF-ß1)-induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G-protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.

Neutrophil extracellular traps trigger alveolar epithelial cell necroptosis through the cGAS-STING pathway during acute lung injury in mice.

Extensive loss of alveolar epithelial cells (AECs) undergoing necroptosis is a crucial mechanism of acute lung injury (ALI), but its triggering mechanism needs to be thoroughly investigated. Neutrophil extracellular traps (NETs) play a significant role in ALI. However, the effect of NETs on AECs' death has not been clarified. Our study found that intratracheal instillation of NETs disrupted lung tissue structure, suggesting that NETs could induce ALI in mice. Moreover, we observed that NETs could trigger necroptosis of AECs in vivo and in vitro. The phosphorylation levels of RIPK3 and MLKL were increased in MLE12 cells after NETs treatment (P < 0.05). Mechanistically, NETs taken up by AECs through endocytosis activated the cGAS-STING pathway and triggered AECs necroptosis. The expression of cGAS, STING, TBK1 and IRF3 were increased in MLE12 cells treated with NETs (P < 0.05). Furthermore, the cGAS inhibitor RU.521 inhibited NETs-triggered AECs necroptosis and alleviated the pulmonary damage induced by NETs in mice. In conclusion, our study demonstrates that NETs taken up by AECs via endocytosis can activate the cGAS-STING pathway and trigger AECs necroptosis to promote ALI in mice. Our findings indicate that targeting the NETs/cGAS-STING/necroptosis pathway in AECs is an effective strategy for treating ALI.

Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53.

Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.

Krüppel-like transcription factor 14 alleviates alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress in pulmonaryfibrosis.

Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.

The Essential Role of Angiogenesis in Adenosine 2A Receptor Deficiency-mediated Impairment of Wound Healing Involving c-Ski via the ERK/CREB Pathways.

Adenosine receptor-mediated signaling, especially adenosine A2A receptor (A2AR) signaling, has been implicated in wound healing. However, the role of endothelial cells (ECs) in A2AR-mediated wound healing and the mechanism underlying this effect are still unclear. Here, we showed that the expression of A2AR substantially increased after wounding and was especially prominent in granulation tissue. The delaying effects of A2AR knockout (KO) on wound healing are due mainly to the effect of A2AR on endothelial cells, as shown with A2AR-KO and EC-A2AR-KO mice. Moreover, the expression of c-Ski, which is especially prominent in CD31-positive cells in granulation tissue, increased after wounding and was decreased by both EC-A2AR KO and A2AR KO. In human microvascular ECs (HMECs), A2AR activation induced EC proliferation, migration, tubule formation and c-Ski expression, whereas c-Ski depletion by RNAi abolished these effects. Mechanistically, A2AR activation promotes the expression of c-Ski through an ERK/CREB-dependent pathway. Thus, A2AR-mediated angiogenesis plays a critical role in wound healing, and c-Ski is involved mainly in the regulation of angiogenesis by A2AR via the ERK/CREB pathway. These findings identify A2AR as a therapeutic target in wound repair and other angiogenesis-dependent tissue repair processes.

New insight into synergistic interaction between the backbone or side chain of xanthan gum and the backbone of Gleditsia sinensis polysaccharide.

In this study, the synergistic effect and weak gel mechanism of XG and Gleditsia sinensis polysaccharide (GSP) in different ratios were studied through the rheological properties, microstructure and molecular simulation based on density functional theory (DFT). The results of rheological properties showed that the mixtures formed a weak gel at the concentration of 0.5 % (w/v), with the synergistic impact peaking at a XG/GSP ratio of 3:7. Weak gels produced by XG and GSP had the intersection of G' and G" within the temperature sweep range, and the largest change in the G' slope at a XG/GSP ratio of 3:7. By calculating the interaction energy, it was found that the backbone of XG was more likely to interact with the backbone of GSP. Furthermore, the XG mainchain intersected with the backbone of GSP in a cross shape ("X" shape). As a result, this paper proposed a possible mechanism for the formation of the XG/GSP weak gel, with XG as the main chain and GSP as the grid point, and the main interaction type being hydrogen bonding, with the van der Waals force also involved. The results provide new insight for designing and producing physical gels with specific interactions in food industry.

Formononetin inhibits IgE by huPlasma/PBMCs and mast cells/basophil activation via JAK/STAT/PI3-Akt pathways.

Rationale: Food allergy is a prevalent disease in the U.S., affecting nearly 30 million people. The primary management strategy for this condition is food avoidance, as limited treatment options are available. The elevation of pathologic IgE and over-reactive mast cells/basophils is a central factor in food allergy anaphylaxis. This study aims to comprehensively evaluate the potential therapeutic mechanisms of a small molecule compound called formononetin in regulating IgE and mast cell activation. Methods: In this study, we determined the inhibitory effect of formononetin on the production of human IgE from peripheral blood mononuclear cells of food-allergic patients using ELISA. We also measured formononetin's effect on preventing mast cell degranulation in RBL-2H3 and KU812 cells using beta-hexosaminidase assay. To identify potential targets of formononetin in IgE-mediated diseases, mast cell disorders, and food allergies, we utilized computational modeling to analyze mechanistic targets of formononetin from various databases, including SEA, Swiss Target Prediction, PubChem, Gene Cards, and Mala Cards. We generated a KEGG pathway, Gene Ontology, and Compound Target Pathway Disease Network using these targets. Finally, we used qRT-PCR to measure the gene expression of selected targets in KU812 and U266 cell lines. Results: Formononetin significantly decreased IgE production in IgE-producing human myeloma cells and PBMCs from food-allergic patients in a dose-dependent manner without cytotoxicity. Formononetin decreased beta-hexosaminidase release in RBL-2H3 cells and KU812 cells. Formononetin regulates 25 targets in food allergy, 51 in IgE diseases, and 19 in mast cell diseases. KEGG pathway and gene ontology analysis of targets showed that formononetin regulated disease pathways, primary immunodeficiency, Epstein-Barr Virus, and pathways in cancer. The biological processes regulated by formononetin include B cell proliferation, differentiation, immune response, and activation processes. Compound target pathway disease network identified NFKB1, NFKBIA, STAT1, STAT3, CCND1, TP53, TYK2, and CASP8 as the top targets regulated at a high degree by formononetin. TP53, STAT3, PTPRC, IL2, and CD19 were identified as the proteins mostly targeted by formononetin. qPCR validated genes of Formononetin molecular targets of IgE regulation in U266 cells and KU812 cells. In U266 cells, formononetin was found to significantly increase the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. In basophils KU812 cells, formononetin significantly increased the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK, TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. Conclusion: These findings comprehensively present formononetin's mechanisms in regulating IgE production in plasma cells and degranulation in mast cells.

B7-H3-Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity Against Solid Tumors.

Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen-presentation pathway, making them a potential "off-the-shelf" cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation. Here, we developed a large-scale clinical-grade manufacturing process for Vδ1T cells and validated the therapeutic potential of B7-H3-CAR-modified Vδ1T cells in treating solid tumors. Co-expression of interleukin-2 with the B7-H3-CAR led to durable anti-tumor activity of Vδ1T cells in vitro and in vivo. In multiple subcutaneous and orthotopic mouse xenograft tumor models, a single intravenous administration of the CAR-Vδ1T cells resulted in complete tumor regression. These modified cells demonstrated significant in vivo expansion and robust homing ability to tumors, akin to natural tissue-resident immune cells. Additionally, the B7-H3-CAR-Vδ1T cells exhibited a favorable safety profile. In conclusion, B7-H3-CAR-modified Vδ1T cells represent a promising strategy for treating solid tumors.

Co-cold extrusion synergized with cysteine for enhancing physicochemical, rheological characteristics and in vitro digestibility of whey protein isolate.

Impacts of co-cold extrusion (≤50 °C) of whey protein isolate (WPI) and cysteine (Cys, 0, 20, 40, 60, 80 and 100 mmol/L) on its physicochemical, in vitro digestion and rheological properties were investigated. As Cys concentration increased, the emulsifying properties and in vitro digestibility of co-extruded WPI-Cys products showed an increasing trend. Specifically, when Cys reached 100 mmol/L, surface hydrophobicity, emulsification activity index (EAI), emulsification stability index (ESI) and in vitro stomach digestibility of the co-extruded WPI-Cys products increased by 205.07%, 77.51%, 193.95% and 71.81% compared with WPI, respectively. Principal component analysis (PCA) results further indicated that co-extruded WPI-Cys at a concentration of 100 mmol/L had the best functional properties. In addition, co-extruded WPI-Cys exhibited the strongest Péclet number (Pe) value and apparent viscosity at a Cys concentration of 100 mmol/L among all samples. Therefore, co-extrusion would be an effective method for modifying WPI, providing whey protein-based ingredients with excellent functional properties for food processing.

Fusiform nanoparticle boosts efficient genetic transformation in Sclerotinia sclerotiorum.

BACKGROUND: Sclerotinia sclerotiorum is a highly destructive phytopathogenic fungus that poses a significant threat to a wide array of crops. The current constraints in genetic manipulation techniques impede a thorough comprehension of its pathogenic mechanisms and the development of effective control strategies. RESULTS: Herein, we present a highly efficient genetic transformation system for S. sclerotiorum, leveraging the use of fusiform nanoparticles, which are synthesized with FeCl3 and 2,6-diaminopyrimidine (DAP). These nanoparticles, with an average longitude length of 59.00 nm and a positively charged surface, facilitate the direct delivery of exogenous DNA into the mycelial cells of S. sclerotiorum, as well as successful integration with stable expression. Notably, this system circumvents fungal protoplast preparation and tedious recovery processes, streamlining the transformation process considerably. Furthermore, we successfully employed this system to generate S. sclerotiorum strains with silenced oxaloacetate acetylhydrolase-encoding gene Ss-oah1. CONCLUSIONS: Our findings demonstrate the feasibility of using nanoparticle-mediated delivery as a rapid and reliable tool for genetic modification in S. sclerotiorum. Given its simplicity and high efficiency, it has the potential to significantly propel genetic research in filamentous fungi, offering new avenues for elucidating the intricacies of pathogenicity and developing innovative disease management strategies.

[Analysis of the Spatiotemporal Evolution of Carbon Reserves in Shaanxi Province Under Different Scenarios in the Future].

To understand the land use development trends in Shaanxi Province under different scenarios and effectively assess the spatiotemporal evolution of terrestrial ecological carbon stocks in Shaanxi Province under land use changes, the study used Markov-FLUS and InVEST models to analyze the impact of land use changes in Shaanxi Province from 2000 to 2020. The impact of carbon storage changes and the spatiotemporal changes in land use structure, carbon storage, and carbon density under three different scenarios were simulated and assessed in Shaanxi Province in 2025 and 2030. The results showed： ① The ROC values of various categories in the coupled Markov-FLUS model were all above 0.7, showing high accuracy and excellent classification performance. The model had a good ability to explain the land use driving factors in the study area, with high accuracy and excellent classification performance. ② From 2000 to 2020, the cultivated land in Shaanxi Province increased significantly. Forest land increased significantly, and the increase in forest land area with high carbon sequestration efficiency caused the carbon storage in Shaanxi Province to increase from 1 546.95 Tg to 1 616.25 Tg. The changes in various regions in Shaanxi Province from 2000 to 2020 were different, among which the carbon storage in Yan'an was significantly increased by 18.89 Tg, whereas the carbon storage in Yulin significantly decreased by 3.29 Tg in 20 years. ③ Altitude, precipitation, and temperature became the main factors affecting the spatiotemporal changes in carbon storage in Shaanxi Province from 2020 to 2030. In three of the years between 2025 and 2030, under different scenarios, the carbon stocks under the ecological priority scenario were 1 632.27 Tg and 1 647.43 Tg, respectively. The carbon storage and its growth rate were significantly higher than in the natural development scenario and the cultivated land protection scenario. ④ The proportion of carbon storage increase areas under the ecological priority scenario was high. In the cultivated land protection scenario, the proportion of reduction areas was lower than that of the natural development scenario, and the distribution of carbon storage was the most balanced. At the same time, the southern and northern areas of the Loess Plateau in northern Shaanxi need to focus on the protection of the ecological environment in future development. The research results can, to a certain extent, provide reference for promoting the construction of ecological Shaanxi and formulating carbon neutral strategic planning.

Simultaneous determination of sixteen phthalic acid esters (PAEs) in soil and evaluation of matrix effect using a QuEChERS/GC/MS-internal standard method.

Phthalic acid esters (PAEs) are emerging pollutants that need to be analyzed precisely. Chromatography-based determination of PAE content in soils are frequently affected by matrix effect, which may limit the quantification of different kinds of PAEs from different types of soil. Here we optimized a QuEChERS protocol combined with gas chromatography-mass spectrometry (GC-MS) for simultaneous determination of 16 PAEs in different soils. PAEs in different type of soils (fluvo-aquic soil, red soil, and black soil) were extracted with acetonitrile followed by GC-MS detection based on quantitative ion internal standard method. All 16 PAEs showed excellent linear relationships with mass peak areas (R2 > 0.99). The limits of detection (LOD) and limits of quantitation (LOQ) of all the samples were in the range of 0.91-66.97 µg/kg and 2.7-200.9 µg/kg, respectively. The accurate test at 0.5, 0.1, and 1.0 mg/kg spiking level recorded recovery rate between 80.11% and 100.99% with relative standard deviations (RSDs) ranging from 0.37 to 8.50% in tested matrices. No significant matrix effect was observed for most tested PAEs. This is a simple method with high sensitivity and strong stability, which is suitable and reproducible for quantifying large number of PAEs in different types of soil.

Treatment of cavitated non-small cell lung cancer presenting as "Halloween pumpkin" following the consecutive NEOADAURA and ADAURA2 strategy: A case report.

Osimertinib is a third-generation tyrosine kinase inhibitor that targets mutant epidermal growth factor receptor (EGFR). The success of FLAURA and ADAURA trials prompted the license of Osimertinib for the treatment of EGFR mutant non-small cell lung cancer (NSCLC) at advanced stage and for patients with stages IB to IIIA disease in post-operative setting. In the present study, we described neoadjuvant use of Osimertinib in an EGFR mutant NSCLC patient with locally metastatic disease (T2aN2M0). Intriguingly, the cavitated NSCLC resembled an impressive"Halloween pumpkin" appearance that dramatically responded to Osimertinib treatment. Downstaging of N2 metastatic disease was reached and surgical resection was scheduled. The post-operative clinical stage was IA3. The patient was recommended to continue Osimertinib adjuvant treatment and our follow-ups showed no signs of disease recurrence. Our case study underscored the feasibility of Osimertinib as a neoadjuvant and adjuvant therapy for patients with locally advanced EGFR mutant NSCLC.

Opioid-free anesthesia with esketamine-dexmedetomidine versus opioid-based anesthesia with propofol-remifentanil in shoulder arthroscopy: a randomized controlled trial.

BACKGROUND: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). METHODS: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. RESULTS: The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P < 0.05) was significantly lower in the OFA group than in the OBA group. Moreover, the severity of PONV was less severe in the OFA group than in the OBA group in PACU (post-anesthesia care unit) (0 [0, 0] vs. 0 [0, 3], P<0.05 ) and in the ward 24 h postoperatively ( 0 [0, 0] vs. 0 [0, 2.25], P<0.05). Additionally, the OFA group experienced a significantly shorter length of stay in the PACU compared to the OBA group (39.4 ± 6.76 min vs. 48.7 ± 7.90 min, P < 0.001). CONCLUSIONS: Compared to the OBA with propofol-remifentanil, the OFA with esketamine- dexmedetomidine proved to be feasible for shoulder arthroscopy, resulting in a reduced incidence of PONV and a shorter duration of stay in the PACU. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (No: ChiCTR2100047355), 12/06/2021.

Computed Tomography Imaging Guided Microenvironment-Responsive Ir@WO3-x Dual-Catalytic Nanoreactor for Selective Radiosensitization.

Radiotherapy (RT) is often administered, either alone or in combination with other therapies, for most malignancies. However, the degree of tumor oxygenation, damage to adjacent healthy tissues, and inaccurate guidance remain issues that result in discontinuation or failure of RT. Here, a multifunctional therapeutic platform based on Ir@WO3-x is developed which simultaneously addresses these critical issues above for precision radiosensitization. Ir@WO3-x nanoreactors exhibit strong absorption of X-ray, acting as radiosensitizers. Moreover, ultrasmall Ir enzyme-mimic nanocrystals (NCs) are decorated onto the surface of the nanoreactor, where NCs have catalyst-like activity and are sensitive to H2O2 in the tumor microenvironment (TME) under near infrared-II (NIR-II) light stimulation. They efficiently catalyze the conversion of H2O2 to O2, thereby ameliorating hypoxia, inhibiting the expression of HIF-1α, and enhancing RT-induced DNA damage in cancerous tissue, further improving the efficiency of RT. Additionally, in response to high H2O2 levels in TME, the Ir@WO3-x nanoreactor also exerts peroxidase-like activity, boosting exogenous ROS, which increases oxidative damage and enhances ROS-dependent death signaling. Furthermore, Ir@WO3-x can serve as a high-quality computed tomography contrast agent due to its high X-ray attenuation coefficient and generation of pronounced tumor-tissue contrast. This report highlights the potential of advanced health materials to enhance precision therapeutic modalities.

Advancements and applications of loop-mediated isothermal amplification technology: a comprehensive overview.

Loop-mediated isothermal amplification (LAMP) is a novel method for nucleic acid detection known for its isothermal properties, high efficiency, sensitivity, and specificity. LAMP employs 4 to 6 primers targeting 6 to 8 regions of the desired sequence, allowing for amplification at temperatures between 60 and 65°C and the production of up to 109 copies within a single hour. The product can be monitored by various methods such as turbidimetry, fluorometry, and colorimetry. However, it faces limitations such as the risk of non-specific amplification, challenges in primer design, unsuitability for short gene sequences, and difficulty in multiplexing. Recent advancements in polymerase and primer design have enhanced the speed and convenience of the LAMP reaction. Additionally, integrating LAMP with technologies like rolling circle amplification (RCA), recombinase polymerase amplification (RPA), and CRISPR-Cas systems has enhanced its efficiency. The combination of LAMP with various biosensors has enabled real-time analysis, broadening its application in point-of-care testing (POCT). Microfluidic technology has further facilitated the automation and miniaturization of LAMP assays, allowing for the simultaneous detection of multiple targets and preventing contamination. This review highlights advancements in LAMP, focusing on primer design, polymerase engineering, and its integration with other technologies. Continuous improvements and integration of LAMP with complementary technologies have significantly enhanced its diagnostic capabilities, making it a robust tool for rapid, sensitive, and specific nucleic acid detection with promising implications for healthcare, agriculture, and environmental monitoring.

Dynamic Gas-Bridged Bond: An Opportunity of Fabricating Dynamic Assembled Materials with Gas.

Gas molecules, as a family of unique polyatomic building blocks, have long been considered hard to involve in molecular assembly or construct assembled materials due to their structural simplicity yet paucity of defined interacting sites. To solve this non-trivial challenge, a core idea is to break the limit of current ways of bonding gas molecules, endowing them with new modes of interactions that match the basic requirements of molecular assembly. In recent years, a new concept, named the dynamic gas-bridged bond (DGB), has emerged, which allows for gas molecules to constitute a dynamic bridging structure between other building blocks with the aid of frustrated Lewis pairs. This makes it possible to harness gas in a supramolecular or dynamic manner. Herein, this perspective discusses distinct dynamic natures of DGBs and manifests their particular functions in various fields, including the control of molecular/polymeric self-assembly nanostructures, creation of multidimensional assembled materials, and recyclable catalysts. The future research direction and challenges of dynamic gas-bridged chemistry toward gas-programmed self-assembly and gas-constructed adaptive materials are highlighted.

The Mitochondrial Distribution and Morphology Family 33 Gene FgMDM33 Is Involved in Autophagy and Pathogenesis in Fusarium graminearum.

The mitochondrial distribution and morphology family 33 gene (MDM33) regulates mitochondrial homeostasis by mediating the mitochondrial fission process in yeast. The wheat head blight Fusarium graminearum contains an FgMdm33 protein that is orthologous to Saccharomyces cerevisiae Mdm33, albeit its function remains unknown. We have reported here the roles of FgMdm33 in regulating fungal morphogenesis, mitochondrial morphology, autophagy, apoptosis, and fungal pathogenicity. The ΔFgmdm33 mutants generated through a homologous recombination strategy in this study exhibited defects in terms of mycelial growth, conidia production, and virulence. Hyphal cells lacking FgMDM33 displayed elongated mitochondria and a dispensable respiratory-deficient growth phenotype, indicating the possible involvement of FgMDM33 in mitochondrial fission. The ΔFgmdm33 mutants displayed a remarkable reduction in the proteolysis of GFP-FgAtg8, whereas the formation of autophagic bodies in the hyphal cells of mutants was recorded under the induction of mitophagy. In addition, the transcriptional expression of the apoptosis-inducing factor 1 gene (FgAIF1) was significantly upregulated in the ΔFgmdm33 mutants. Cumulatively, these results indicate that FgMDM33 is involved in mitochondrial fission, non-selective macroautophagy, and apoptosis and that it regulates fungal growth, conidiation, and pathogenicity of the head blight pathogen.

Four novel variants identified in the ACADVL gene causing very-long-chain acyl-coenzyme A dehydrogenase deficiency in four unrelated Chinese families.

Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD, are reported and discussed in this article. Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein. Result: A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation. Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.