The alteration of the structure and macroscopic mechanical response of porcine patellar tendon by elastase digestion.

Background: The treatment of patellar tendon injury has always been an unsolved problem, and mechanical characterization is very important for its repair and reconstruction. Elastin is a contributor to mechanics, but it is not clear how it affects the elasticity, viscoelastic properties, and structure of patellar tendon. Methods: The patellar tendons from six fresh adult experimental pigs were used in this study and they were made into 77 samples. The patellar tendon was specifically degraded by elastase, and the regional mechanical response and structural changes were investigated by: (1) Based on the previous study of elastase treatment conditions, the biochemical quantification of collagen, glycosaminoglycan and total protein was carried out; (2) The patellar tendon was divided into the proximal, central, and distal regions, and then the axial tensile test and stress relaxation test were performed before and after phosphate-buffered saline (PBS) or elastase treatment; (3) The dynamic constitutive model was established by the obtained mechanical data; (4) The structural relationship between elastin and collagen fibers was analyzed by two-photon microscopy and histology. Results: There was no statistical difference in mechanics between patellar tendon regions. Compared with those before elastase treatment, the low tensile modulus decreased by 75%-80%, the high tensile modulus decreased by 38%-47%, and the transition strain was prolonged after treatment. For viscoelastic behavior, the stress relaxation increased, the initial slope increased by 55%, the saturation slope increased by 44%, and the transition time increased by 25% after enzyme treatment. Elastin degradation made the collagen fibers of patellar tendon become disordered and looser, and the fiber wavelength increased significantly. Conclusion: The results of this study show that elastin plays an important role in the mechanical properties and fiber structure stability of patellar tendon, which supplements the structure-function relationship information of patellar tendon. The established constitutive model is of great significance to the prediction, repair and replacement of patellar tendon injury. In addition, human patellar tendon has a higher elastin content, so the results of this study can provide supporting information on the natural properties of tendon elastin degradation and guide the development of artificial patellar tendon biomaterials.

Preparation of porous polylactic acid nanofibers and application in non-electret high-efficiency filtration composites.

Air pollution caused by fine particulate matter (PM0.3) has drawn increasing attention as an overwhelming threat to public health. Electret treatment is commonly used to improve the filtration performance of commercial fibrous filter materials by enhancing the electrostatic adsorption effect, but it is greatly affected by environmental factors (especially humidity). Moreover, filter materials are generally non-degradable and non-recyclable, causing serious environmental pollution. Herein, a strategy to manufacture fully degradable polylactic acid (PLA) filtration composites based on porous PLA nanofibers prepared by electrospinning was investigated in this study. Porous, bead-on-string and conventional PLA nanofibers could be obtained by adjusting spinning condition parameters. The porous PLA nanofibers exhibited 9.8 times greater specific surface area (24.01 m2 g-1) and 18 times more cumulative pore volume (0.108 cm3 g-1) than conventional PLA nanofibers. More importantly, fibrous filtration composites based on porous PLA nanofibers possessed a high PM0.3 filtration efficiency (99.9989%), low pressure drop (90.35 Pa) and high air permeability (72.4 Pa-1) at an air flow rate of 32 L min-1 without electret treatment. The fibrous filtration composites based on conventional or bead-on-string PLA nanofibers also exhibited excellent filtration performance (>99.99%), but the associated high pressure drop and low air permeability limited their application.

Concrete Highway Crack Detection Based on Visible Light and Infrared Silicate Spectrum Image Fusion.

Cracks provide the earliest and most immediate visual response to structural deterioration of asphalt pavements. Most of the current methods for crack detection are based on visible light sensors and convolutional neural networks. However, such an approach obviously limits the detection to daytime and good lighting conditions. Therefore, this paper proposes a crack detection technique cross-modal feature alignment of YOLOV5 based on visible and infrared images. The infrared spectrum characteristics of silicate concrete can be an important supplement. The adaptive illumination-aware weight generation module is introduced to compute illumination probability to guide the training of the fusion network. In order to alleviate the problem of weak alignment of the multi-scale feature map, the FA-BIFPN feature pyramid module is proposed. The parallel structure of a dual backbone network takes 40% less time to train than a single backbone network. As determined through validation on FLIR, LLVIP, and VEDAI bimodal datasets, the fused images have more stable performance compared to the visible images. In addition, the detector proposed in this paper surpasses the current advanced YOLOV5 unimodal detector and CFT cross-modal fusion module. In the publicly available bimodal road crack dataset, our method is able to detect cracks of 5 pixels with 98.3% accuracy under weak illumination.

Environmental Dyeing and Functionalization of Silk Fabrics with Natural Dye Extracted from Lac.

Most traditional synthetic dyes and functional reagents used in silk fabrics are not biodegradable and lack green environmental protection. Natural dyes have attracted more and more attention because of their coloring, functionalization effects, and environmental benefits. In this study, natural dyes were extracted from lac and used for coloring and functionalization in silk fabrics without any other harmful dyes. The extraction conditions were studied and analyzed by the univariate method. The optimal extraction process was that the volume ratio of ethanol to water was 60:40 with a solid-liquid ratio of 1:10, and reacting under the neutrality condition for 1 h at 70 °C. Silk fabric can be dyed dark owing to the certain lifting property of lac. After being dyed by Al3+ post-medium, the levels of the washing fastness, light fastness, and friction fastness of silk fabric are all above four with excellent fastness. The results show that the dyed silk fabrics have good UV protection, antioxidation, and antibacterial properties. The UV protection coefficient UPF is 42.68, the antioxidant property is 98.57%, and the antibacterial property can reach more than 80%. Therefore, the dyeing and functionalization of silk fabrics by utilizing naturally lac dyes show broad prospects in terms of the application of green sustainable dyeing and functionalization.

The Preparation and Performance Study of Polyamide Film Based on PDA@MWCNTs/PVDF Porous Support Layer.

It is urgent to develop a polyamide (PA) thin-film composite (TFC) membrane with a new method in this study by designing and constructing a new nanomaterial support layer instead of the conventional support layer. Polydopamine-wrapped single-walled carbon nanotubes (PDA@MWCNTs) as the place of the polymerization reaction can optimize the PA film structure and performance. The resulting composite membrane presents a higher water flux of 15.8 L·m-2·h-1·bar-1 and a rejection rate of 97% to Na2SO4, simultaneously maintaining this high separation performance in 300 min. It is a new ideal to construct novel support layer by using inorganic nanoparticles and organic polymer nanofiber membranes.

Synthesis of grafted bromoisobutyryl esterified starch using electron transfer atom transfer radical polymerization method with high-performance adhesion and film properties.

Nowadays, few investigations on the process parameters of grafted starch synthesized using electron transfer atom transfer radical polymerization (ARGET ATRP) and its applications in warp sizing and paper-making are presented. Therefore, this study aimed to survey the appropriate process parameters of bromoisobutyryl esterified starch-g-poly(acrylic acid) (BBES-g-PAA) synthesized by the ARGET ATRP, and also aimed to provide a new biobased BBES-g-PAA adhesive. The appropriate synthesis process parameters were 1.2, 0.32, and 0.6 in the molar ratios of vitamin C, CuBr2, and pentamethyldivinyltriamine to BBES, respectively, at 40 °C for 5 h. The BBES-g-PAA samples with a grafting ratio range of 4.63-14.14 % exhibited bonding forces of 57.8-64.6 N to wool fibers [55.5 N (BBES) and 53.8 N (ATS)], and their films showed breaking elongations of 3.29-3.80 % [2.74 % (BBES) and 2.49 % (ATS)] and tensile strengths of 29.1-25.4 MPa [30.4 MPa (BBES) and 34.7 MPa (ATS)]. Compared with BBES, significantly increased bonding forces and film elongations, and decreased film strengths for the BBES-g-PAA samples with grafting ratios ≥10.54 % were displayed (p < 0.05). The time (100-42 s) taken for the BBES-g-PAA films was significantly shorter than that of ATS (246 s) and BBES (196 s) films (p < 0.05), corresponding to better desizability.

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo.

Nuclear factor erythroid 2 like (Nfe2l) gene family members 1-3 mediate cellular response to oxidative stress, including in the central nervous system (CNS). However, neuronal functions of Nfe2l3 are unknown. Here, we comparatively evaluated expression of Nfe2l1, Nfe2l2, and Nfe2l3 in singe cell RNA-seq (scRNA-seq)-profiled cortical and retinal ganglion cell (RGC) CNS projection neurons, investigated whether Nfe2l3 regulates neuroprotection and axon regeneration after CNS injury in vivo, and characterized a gene network associated with Nfe2l3 in neurons. We showed that, Nfe2l3 expression transiently peaks in developing immature cortical and RGC projection neurons, but is nearly abolished in adult neurons and is not upregulated after injury. Furthermore, within the retina, Nfe2l3 is enriched in RGCs, primarily neonatally, and not upregulated in injured RGCs, whereas Nfe2l1 and Nfe2l2 are expressed robustly in other retinal cell types as well and are upregulated in injured RGCs. We also found that, expressing Nfe2l3 in injured RGCs through localized intralocular viral vector delivery promotes neuroprotection and long-distance axon regeneration after optic nerve injury in vivo. Moreover, Nfe2l3 provided a similar extent of neuroprotection and axon regeneration as viral vector-targeting of Pten and Klf9, which are prominent regulators of neuroprotection and long-distance axon regeneration. Finally, we bioinformatically characterized a gene network associated with Nfe2l3 in neurons, which predicted the association of Nfe2l3 with established mechanisms of neuroprotection and axon regeneration. Thus, Nfe2l3 is a novel neuroprotection and axon regeneration-promoting factor with a therapeutic potential for treating CNS injury and disease.

SARS-CoV-2 spike protein receptor binding domain promotes IL-6 and IL-8 release via ATP/P2Y2 and ERK1/2 signaling pathways in human bronchial epithelia.

The spike protein of SARS-CoV-2 as well as its receptor binding domain (RBD) has been demonstrated to be capable of activating the release of pro-inflammatory mediators in endothelial cells and immune cells such as monocytes. However, the effects of spike protein or its RBD on airway epithelial cells and mechanisms underlying these effects have not been adequately characterized. Here, we show that the RBD of spike protein alone can induce bronchial epithelial inflammation in a manner of ATP/P2Y2 dependence. Incubation of human bronchial epithelia with RBD induced IL-6 and IL-8 release, which could be inhibited by antibody. The incubation of RBD also up-regulated the expression of inflammatory indicators such as ho-1 and mkp-1. Furthermore, ATP secretion was observed after RBD treatment, P2Y2 receptor knock down by siRNA significantly suppressed the IL-6 and IL-8 release evoked by RBD. Additionally, S-RBD elevated the phosphorylation level of ERK1/2, and the effect that PD98059 can inhibit the pro-inflammatory cytokine release suggested the participation of ERK1/2. These novel findings provide new evidence of SARS-CoV-2 on airway inflammation and introduce purinergic signaling as promising treatment target.

Dexamethasone-Loaded Lipid Calcium Phosphate Nanoparticles Treat Experimental Colitis by Regulating Macrophage Polarization in Inflammatory Sites.

Background: The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. Purpose: A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Methods: Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. Results: The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. Conclusion: The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.

Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease.

BACKGROUND: Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. METHODS: Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. RESULTS: We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. CONCLUSIONS: Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors.

The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases.

AIM OF THE STUDY: Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined. MATERIALS AND METHODS: The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression. RESULTS: Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM. CONCLUSIONS: Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis.

Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo.

Numerous micro-RNAs (miRNAs) affect neurodevelopment and neuroprotection, but potential roles of many miRNAs in regulating these processes are still unknown. Here, we used the retinal ganglion cell (RGC) central nervous system (CNS) projection neuron and optic nerve crush (ONC) injury model, to optimize a mature miRNA arm-specific quantification method for characterizing the developmental regulation of miR-1247-5p in RGCs, investigated whether injury affects its expression, and tested whether upregulating miR-1247-5p-mimic in RGCs promotes neuroprotection and axon regeneration. We found that, miR-1247-5p is developmentally-downregulated in RGCs, and is further downregulated after ONC. Importantly, RGC-specific upregulation of miR-1247-5p promoted neuroprotection and axon regeneration after injury in vivo. To gain insight into the underlying mechanisms, we analyzed by bulk-mRNA-seq embryonic and adult RGCs, along with adult RGCs transduced by miR-1247-5p-expressing viral vector, and identified developmentally-regulated cilial and mitochondrial biological processes, which were reinstated to their embryonic levels in adult RGCs by upregulation of miR-1247-5p. Since axon growth is also a developmentally-regulated process, in which mitochondrial dynamics play important roles, it is possible that miR-1247-5p promoted neuroprotection and axon regeneration through regulating mitochondrial functions.

Palladium-Catalyzed Synthesis of Indanone via C-H Annulation Reaction of Aldehydes with Norbornenes.

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.

An updated review of the genus Rhododendron since 2010: Traditional uses, phytochemistry, and pharmacology.

Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development.

Paradoxical effects on ice nucleation are intrinsic to a small winter flounder antifreeze protein.

Antifreeze proteins (AFPs) bind to ice in solutions, resulting in non-colligative freezing point depression; however, their effects on ice nucleation are not well understood. The predominant plasma AFP of winter flounder (Pseudopleuronectes americanus) is AFP6, which is an amphiphilic alpha helix. In this study, AFP6 and modified constructs were produced as fusion proteins in Escherichia coli, subjected to proteolysis when required and purified prior to use. AFP6 and its recombinant fusion precursor generated similar thermal hysteresis and bipyramidal ice crystals, whereas an inactive mutant AFP6 produced hexagonal crystals and no hysteresis. Circular dichroism spectra of the wild-type and mutant AFP6 were consistent with an alpha helix. The effects of these proteins on ice nucleation were investigated alongside non-AFP proteins using a standard droplet freezing assay. In the presence of nucleating AgI, modest reductions in the nucleation temperature occurred with the addition of mutant AFP6, and several non-AFPs, suggesting non-specific inhibition of AgI-induced ice nucleation. In these experiments, both AFP6 and its recombinant precursor resulted in lower nucleation temperatures, consistent with an additional inhibitory effect. Conversely, in the absence of AgI, AFP6 induced ice nucleation, with no other proteins showing this effect. Nucleation by AFP6 was dose-dependent, reaching a maximum at 1.5 mM protein. Nucleation by AFP6 also required an ice-binding site, as the inactive mutant had no effect. Furthermore, the absence of nucleation by the recombinant precursor protein suggested that the fusion moiety was interfering with the formation of a surface capable of nucleating ice.

Generalized inverse matrix-graphic deep learning algorithm for multispectral pyrometer temperature inversion.

The multispectral radiometric temperature measurement technique is affected by the unknown emissivity, and there is no multispectral radiometric temperature inversion algorithm applicable to any scene or target. To address the above problems, this paper converts the multispectral radiometric temperature inversion problem into an image recognition problem containing the temperature information to be measured, and proposes a graphical multispectral radiometric temperature adaptive inversion algorithm. In this paper, we use the difference between spectral channels to convert the one-dimensional radiation data into a two-dimensional radiation map; use the generalized inverse to obtain the spectral emissivity distribution features, fuse them with the two-dimensional radiation map, and use an improved deep learning network to achieve adaptive temperature inversion. It is experimentally verified that the algorithm proposed in this paper can achieve simultaneous inversion of temperature and emissivity for any scene or target with sufficient data set.

The anti-leukemia activity and mechanisms of shikonin: a mini review.

Leukemia encompasses a group of highly heterogeneous diseases that pose a serious threat to human health. The long-term outcome of patients with leukemia still needs to be improved and new effective therapeutic strategies continue to be an unmet clinical need. Shikonin (SHK) is a naphthoquinone derivative that shows multiple biological function includes anti-tumor, anti-inflammatory, and anti-allergic effects. Numerous studies have reported the anti-leukemia activity of SHK during the last 3 decades and there are studies showing that SHK is particularly effective towards various leukemia cells compared to solid tumors. In this review, we will discuss the anti-leukemia effect of SHK and summarize the underlying mechanisms. Therefore, SHK may be a promising agent to be developed as an anti-leukemia drug.

Strategy of functional nucleic acids-mediated isothermal amplification for detection of foodborne microbial contaminants: A review.

Foodborne microbial contamination (FMC) is the leading cause of food poisoning and foodborne illness. The foodborne microbial detection methods based on isothermal amplification have high sensitivity and short detection time, and functional nucleic acids (FNAs) could extend the detectable object of isothermal amplification to mycotoxins. Therefore, the strategy of FNAs-mediated isothermal amplification has been emergingly applied in biosensors for foodborne microbial contaminants detection, making biosensors more sensitive with lower cost and less dependent on nanomaterials for signal output. Here, the mechanism of six isothermal amplification technologies and their application in detecting FMC is firstly introduced. Then the strategy of FNAs-mediated isothermal amplification is systematically discussed from perspectives of FNAs' versatility including recognition elements (Aptamer, DNAzyme), programming tools (DNA tweezer, DNA walker and CRISPR-Cas) and signal units (G-quadruplex, FNAs-based nanomaterials). Finally, challenges and prospects are presented in terms of addressing the issue of nonspecific amplification reaction, developing better FNAs-based sensing elements and eliminating food matrix effects.

The romantic history of signaling pathway discovery in cell death: an updated review.

Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities.