Construction of a Label-Detection Integrated Visual Probe to Reveal the Double-Edged Sword Principle of Ferroptosis in Liver Injury.

Ferroptosis has been confirmed as a potential mediator and an indicator of the severity of liver injury. Despite the fruitful results, there are still two deficiencies in the research on the association between ferroptosis and liver injury. First, iron ions are usually selected as the target bioanalyte, but its detection based on a fluorescent probe is interfered with by specific chemical reaction mechanisms, leading to low sensitivity and poor physiological stability. Second, more efforts were focused on the harmful effects of ferroptosis on liver injury and less involved in the therapeutic value of ferroptosis for liver injury. Hence, in this work, we proposed a new nonreactive analyte (mitochondrial viscosity) as an analysis marker, which can circumvent the challenges caused by specific reaction mechanisms of iron ions. Meanwhile, we constructed a novel label-detection integrated visual probe (VPF) to explore the feasibility of ferroptosis in the treatment of liver injury. As expected, we not only successfully traced the dynamic changes in mitochondrial viscosity but also visualized the changes in cell morphology during induced and inhibited ferroptosis. Conspicuously, this work revealed that liver injury can be alleviated by regulating ferroptosis, confirming the therapeutic value of ferroptosis in liver injury. In addition, a complex biological communication network between ferroptosis and liver injury was constructed by western blotting, providing an important theoretical mechanism for revealing their double-edged sword relationship. This study not only provides a new strategy for studying the complex relationship between ferroptosis and liver injury but also facilitates the future treatment of liver injury.

Investigating the Therapeutic Effects of Ferroptosis on Myocardial Ischemia-Reperfusion Injury Using a Dual-Locking Mitochondrial Targeting Strategy.

Research on ferroptosis in myocardial ischemia/reperfusion injury (MIRI) using mitochondrial viscosity as a nexus holds great promise for MIRI therapy. However, high-precision visualisation of mitochondrial viscosity remains a formidable task owing to the debilitating electrostatic interactions caused by damaged mitochondrial membrane potential. Herein, we propose a dual-locking mitochondria-targeting strategy that incorporates electrostatic forces and probe-protein molecular docking. Even in damaged mitochondria, stable and precise visualisation of mitochondrial viscosity in triggered and medicated MIRI was achieved owing to the sustained driving forces (e.g., pi-cation, pi-alkyl interactions, etc.) between the developed probe, CBS, and the mitochondrial membrane protein. Moreover, complemented by a western blot, we confirmed that ferrostatin-1 exerts its therapeutic effect on MIRI by improving the system xc-/GSH/GPX4 antioxidant system, confirming the therapeutic value of ferroptosis in MIRI. This study presents a novel strategy for developing robust mitochondrial probes, thereby advancing MIRI treatment.

Overexpression of TYRO3 indicates poor prognosis and induces gastric cancer progression via AKT-mTOR pathway.

Gastric cancer (GC) is among of the leading causes of cancer mortality worldwide. This is because many patients are diagnosed with advanced GC and postoperative radiotherapy and chemotherapy have also exhibited limited effects on GC. TYRO3 has been considered carcinogenic and a potential therapeutic target for GC. However, TYRO3 function and mechanism in GC remains elusive. The study results indicated that TYRO3 was aberrantly elevated in GC tissues and predicted poor prognosis. TYRO3 is closely associated with clinicopathological indicators in GC tissues such as lymph node metastasis, venous invasion, neural invasion, and the tumor-node-metastasis stage. In addition, TYRO3 expression levels are closely related to the AKT-mTOR pathway in GC tissues. Moreover, the oncogenic role of TYRO3 was determined through in vitro and in vivo functional assays, and knockdown of the TYRO3 expression level in GC cell lines can effectively suppress the AKT-mTOR pathway and inhibit tumor cell proliferation and migration. In conclusion, this study provides a theoretical basis for establishing the potential association and regulatory mechanism between TYRO3 and AKT-mTOR and offers a new strategy for GC-targeted therapy.

Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.

Increased glucocorticoid (GC) levels act as a master contributor to central obesity in estrogen-depleted females; however, what factors cause their increased GC production is unclear. Given (1) liver fibroblast growth factor 21 (FGF21) and GCs regulate each other's production in a feed-forward loop, and (2) circulating FGF21 and GCs are parallelly increased in menopausal women and ovariectomized mice, we thus hypothesized that elevation of hepatic FGF21 secretion causes increased GGs production in estrogen-depleted females. Using the ovariectomized mice as a model for menopausal women, we found that ovariectomy (OVX) increased circulating corticosterone levels, which in turn increased visceral adipose Hsd11b1 expression, thus causing visceral obesity in females. In contrast, liver-specific FGF21 knockout (FGF21 LKO) completely reversed OVX-induced high GCs and high visceral adipose Hsd11b1 expression, thus abrogating OVX-induced obesity in females. Even though FGF21 LKO failed to rescue OVX-induced dyslipidemia, hepatic steatosis, and insulin resistance. What's worse, FGF21 LKO even further exacerbated whole-body glucose metabolic dysfunction as evidenced by more impaired glucose and pyruvate tolerance and worsened insulin resistance. Mechanically, we found that FGF21 LKO reduced circulating insulin levels, thus causing the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes in OVX mice. Collectively, our results suggest that liver FGF21 plays an essential role in mediating OVX-induced central obesity by promoting GC production. However, lack of liver FGF21 signaling reduces insulin production and in turn causes the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes, highlighting a detrimental role for hepatic FGF21 signals in mediating the development of central obesity but a beneficial role in preventing metabolic abnormality from further exacerbation in estrogen-depleted females.

A Multiple-Target Simultaneous Detection Method for Immunosorbent Assay and Immunospot Assay.

Enzyme-linked immunosorbent assay (ELISA) is one of the most common methods in biological studies, and enzyme-linked immunospot (ELISpot) is a method to measure specific cell numbers by detecting protein secretion at a single-cell level. However, these two current methods can only detect one signal at one time and the sensitivity is not high enough to test low-concentration samples, which are major shortcomings in systematically analyzing the samples of interest. Herein, we demonstrated fluorescence-based oligo-linked immunosorbent assay (FOLISA) and fluorescence-based oligo-linked immunospot (FOLISPOT), which utilized DNA-barcoded antibodies to provide a highly multiplexed method with signal amplification. Signal amplification and simultaneous multiple-target detection were achieved by DNA complementary pairing and modular orthogonal DNA concatemers. By comparing FOLISA with traditional ELISA and comparing FOLISPOT with traditional ELISPOT, we found that the detection sensitivities of FOLISA and FOLISPOT are much higher than those of traditional ELISA and ELISPOT. The detection limit of ELISA is around 3 pg/mL, and the detection limit of FOLISA is below 0.06 pg/mL. FOLISPOT can detect more spots than ELISPOT and can detect targets that are undetectable for ELISPOT. Furthermore, FOLISA and FOLISPOT allowed sequential detection of multiple targets by using a single dye or multiple dyes in one round and sequential detection in multiple rounds. Thus, FOLISA and FOLISPOT enabled simultaneous detection of a large number of targets, significantly improved the detection sensitivity, and overcame the shortcomings of ELISA and ELISPOT. Overall, FOLISA and FOLISPOT presented effective and general platforms for rapid and multiplexed detection of antigens or antibodies with high sensitivity, either in laboratory tests or potentially in clinic tests.

Impact of the heat load on the laser performance of chirally-coupled-core fibers.

As the heat load within the central core of chirally-coupled-core (CCC) fibers will change the pre-designed refractive index profile through the thermo-optic effect, its impact on the laser performance of CCC fibers is investigated. Analysis and simulation results on two typical CCC fibers show that the effects of the heat load include the modal loss reduction and the transmission spectrum drift. The former comes from the thermal lensing effect in the central core, and the latter is caused by the change in the refractive index difference between the central core and the side core. Considering the non-uniform axial heat distribution in the actual laser operation, the overall laser performance of CCC fibers with different pump power is simulated. It is found that, because of the high pre-designed high-order mode loss, the single-mode operation of CCC fibers will be maintained but the slope efficiency may reduce dramatically if the fundamental mode loss is strongly dependent on the heat load.

Mode instabilities in Yb:YAG crystalline fiber amplifiers.

Mode instabilities (MI) threshold in the Yb:YAG crystalline fiber amplifier is simulated by a full numerical model. The propagation of signal fields is simulated by the finite-difference beam-propagation method combined with the rate equations, and the time-dependent heat equation is solved by the alternating-direction-implicit method. Considering the strong temperature-dependent laser performance of Yb:YAG, an iterative method is applied to reach the steady state of Yb:YAG, the crystalline fiber amplifier, before the simulation of MI behavior. The simulated MI thresholds in Yb:YAG crystalline fiber amplifiers are found to be at least 28 times of those in Yb-doped silica-glass fiber amplifiers, up to tens of kilowatts. Simulation results show that, in addition to the expected higher thermal conductivity and lower thermo-optic coefficient, strong gain saturation also plays an important role in the high MI threshold of the Yb:YAG crystalline fiber.

Sensor Data-Driven Bearing Fault Diagnosis Based on Deep Convolutional Neural Networks and S-Transform.

Accurate and timely bearing fault diagnosis is crucial to decrease the probability of unexpected failures of rotating machinery and improve the efficiency of its scheduled maintenance. Since convolutional neural networks (CNN) have poor feature extraction capability for sensor data with 1D format, CNN combined with signal processing algorithm is often adopted for fault diagnosis. This increases manual conversion work and expertise dependence while reducing the feasibility and robustness of the corresponding fault diagnosis method. In this paper, a novel sensor data-driven fault diagnosis method is proposed by fusing S-transform (ST) algorithm and CNN, namely ST-CNN. First of all, a ST layer is designed based on S-transform algorithm. In the ST layer, sensor data is automatically converted into 2D time-frequency matrix without manual conversion work. Then, a new ST-CNN model is constructed, and the time-frequency coefficient matrixes are inputted into the constructed ST-CNN model. After the training process of the ST-CNN model is completed, the classification layer such as softmax performs the fault diagnosis. Finally, the diagnosis performance of the proposed method is evaluated by using two public available datasets of bearings. The experimental results show that the proposed method performs the higher and more robust diagnosis performance than other existing methods.

Finite-difference beam-propagation method for anisotropic waveguides with torsional birefringence.

A new three-dimensional finite-difference (FD)-based beam propagation method (BPM) is proposed for simulating optical propagation in weakly guiding waveguides with torsional birefringence, which cannot be simulated by existing FD-BPM algorithms. We also demonstrate that this new BPM algorithm is capable of obtaining eigenmode solutions in a helically-symmetric z-dependent waveguide structure with torsional birefringence.

All-in-fiber method of generating orbital angular momentum with helically symmetric fibers.

An all-in-fiber method of generating orbital angular momentum (OAM) is proposed. A simple device composed with a section of helically symmetric fiber and another section of regular fiber is designed to convert input light to optical vortices. Finite element method calculation of first- and second-order OAM generation based on the coordinates transformation technique is taken to show that the eigenmodes of the helically symmetric fiber structures carry orbital and spin angular momentum. Simulation using the self-developed beam propagation method algorithm is also performed to verify the orbital angular momentum generation and evaluate the performance of the OAM generator.

All-in-fiber method of generating orbital angular momentum with helically symmetric fibers: publisher's note.

This publisher's note amends a figure caption in Appl. Opt.57, 8182 (2018)APOPAI0003-693510.1364/AO.57.008182.

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice.

This study aimed to assess the impact of Lactobacillaceae (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as Bacteroides, Blautia, Akkermansia, and Faecalibaculum, and significantly decreased the abundance of Proteus. Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote ß-oxidation by increasing the levels of SCFAs. Faecalibaculum, Blautia, Bacteroides, and Akkermansia exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. Faecalibaculum, Blautia, Bacteroides, and Akkermansia may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of Lactobacillaceae, inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.

High-strength and crack-free welding of 2024 aluminium alloy via Zr-core-Al-shell wire.

The 2000 series aluminium alloys are qualified for widespread use in lightweight structures, but solidification cracking during fusion welding has been a long-standing issue. Here, we create a zirconium (Zr)-core-aluminium (Al)-shell wire (ZCASW) and employ the oscillating laser-arc hybrid welding technique to control solidification during welding, and ultimately achieve reliable and crack-free welding of 2024 aluminium alloy. We select Zr wires with an ideal lattice match to Al based on crystallographic information and wind them by the Al wires with similar chemical components to the parent material. Crack-free, equiaxed (where the length, width and height of the grains are roughly equal), fine-grained microstructures are acquired, thereby considerably increasing the tensile strength over that of conventional fusion welding joints, and even comparable to that of friction stir welding joints. This work has important engineering application value in welding of high-strength aluminum alloys.

Deep Bidirectional Recurrent Neural Networks Ensemble for Remaining Useful Life Prediction of Aircraft Engine.

Remaining useful life (RUL) prediction of aircraft engine (AE) is of great importance to improve its reliability and availability, and reduce its maintenance costs. This article proposes a novel deep bidirectional recurrent neural networks (DBRNNs) ensemble method for the RUL prediction of the AEs. In this method, several kinds of DBRNNs with different neuron structures are built to extract hidden features from sensory data. A new customized loss function is designed to evaluate the performance of the DBRNNs, and a series of the RUL values is obtained. Then, these RUL values are reencapsulated into a predicted RUL domain. By updating the weights of elements in the domain, multiple regression decision tree (RDT) models are trained iteratively. These models integrate the predicted results of different DBRNNs to realize the final RUL prognostics with high accuracy. The proposed method is validated by using C-MAPSS datasets from NASA. The experimental results show that the proposed method has achieved more superior performance compared with other existing methods.

Surface plasmon field enhanced upconversion luminescence for the screening and detection of phenolic environmental estrogens.

The endocrine system's interference caused by environmental estrogens (EEs) residue in food is a topic of public concern. Here, we construct an aptasensor for the sensitive detection of EEs based on luminescence resonance energy transfer (LRET). With MoS2 nanosheets acting as the energy acceptor and upconversion luminescence nanoparticles@gold nanoparticles (UCNPs@Au) as the luminescence donor, autofluorescence from food is prevented from interfering. The in-situ deposition of AuNPs not only induces local field enhancement to significantly increase the luminescence intensity of UCNPs, but also conduces to the modification of aptamer through Au-S bond. This aptasensor can respond to multiple estrogens thanks to the choice of a universal aptamer that recognizes phenolic hydroxyl group, and it offers the probability to screen unidentified phenolic estrogens. This method has a high sensitivity and a low limit of detection (LOD), and the satisfactory recovery rates acquired from water and milk samples confirmed its considerable application value.

Novel mutation in exon11 of PRKCG (SCA14): A case report.

Introduction: PRKCG mutations have been implicated in the pathogenesis of spinocerebellar ataxia type 14 (SCA14), which is a rare autosomal dominant disease marked by cerebellar degeneration, dysarthria, and nystagmus. Until now, there has never been a report of patients with mutations of c.1232G>C worldwide. Case description: We report a case of a 30-year-old Chinese man with episodic dystaxia, speech disorder, and cognitive impairment; however, his father exclusively exhibited a speech disorder regardless of the same mutation. Whole-exome sequencing revealed a heterozygous c.1232G>C (p.G411A) variant of PRKCG. Conclusion: This case presents an extended genotype and phenotype of SCA14, and emphasizes the importance of gene sequencing in patients with spinocerebellar ataxia.

An update on the role of thioredoxin-interacting protein in diabetic kidney disease: A mini review.

Thioredoxin-interacting protein (TXNIP) was first isolated from Vitamin D3-exposed HL60 cells. TXNIP is the main redox-regulating factor in various organs and tissues. We begin with an overview of the TXNIP gene and protein information, followed by a summary of studies that have shown its expression in human kidneys. Then, we highlight our current understanding of the effect of TXNIP on diabetic kidney disease (DKD) to improve our understanding of the biological roles and signal transduction of TXNIP in DKD. Based on the recent review, the modulation of TXNIP may be considered as a new target in the management of DKD.

Photopolymerizable, immunomodulatory hydrogels of gelatin methacryloyl and carboxymethyl chitosan as all-in-one strategic dressing for wound healing.

Microenvironment regeneration in wound tissue is crucial for wound healing. However, achieving desirable wound microenvironment regeneration involves multiple stages, including hemostasis, inflammation, proliferation, and remodeling. Traditional wound dressings face challenges in fully manipulating all these stages to achieve quick and complete wound healing. Herein, we present a VEGF-loaded, versatile wound dressing hydrogel based on gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCS), which could be easily fabricated using UV irradiation. The newly designed GelMA-CMCS@VEGF hydrogel not only exhibited strong tissue adhesion capacity due to the interactions between CMCS active groups and biological tissues, but also possessed desirable extensible properties for frequently moving skins and joints. Furthermore, the hydrogel demonstrates exceptional abilities in blood cell coagulation, hemostasis and cell recruitment, leading to the promotion of endothelial cells proliferation, adhesion, migration and angiogenesis. Additionally, in vivo studies demonstrated that the hydrogel drastically shortened hemostatic time, and achieved satisfactory therapeutic efficacy by suppressing inflammation, modulating M1/M2 polarization of macrophages, significantly promoting collagen deposition, stimulating angiogenesis, epithelialization and tissue remodeling. This work contributes to the design of versatile hydrogel dressings for rapid and complete wound healing therapy.

Prognosis value and positive association of Rab1A/IL4Rα aberrant expression in gastric cancer.

Gastric cancer (GC) is the most common gastrointestinal cancer and the leading cause of worldwide cancer-associated mortality. Several GC patients are diagnosed at the advanced stage with an unsatisfactory 5-year survival rate. Rab1A was significantly associated with IL4Rα expression in non-small cell lung cancer. However, their potential correlation in expression and prognosis remains largely unknown in GC. In this study, Rab1A/IL-4Rα was significantly increased in GC than in para-cancerous tissues, and Rab1A/IL-4Rα overexpression caused poor prognosis among GC patients. Rab1A expression was significantly correlated with IL-4Rα expression in GC tissues, as determined by IHC analysis. In addition, the mRNA expression of Rab1A was closely linked with the IL-4Rα mRNA expression in GC tissue expressed by qPCR. Furthermore, the Kaplan-Meier analysis demonstrated that the group with negative Rab1A and IL-4Rα expression had longer 5-year survival rates than the other group. Besides, the group with positive Rab1A and IL-4Rα expression had a worse prognosis than the other group. Finally, nomograms revealed the overall 3 and 5-year survival determined crucial roles of Rab1A/IL-4Rα expression in predicting the prognosis of GC patients. Therefore, Rab1A/IL-4Rα is vital in GC, providing a novel perspective on targeted GC therapy.

TYRO3 promotes tumorigenesis and drug resistance in colorectal cancer by enhancing the epithelial-mesenchymal transition process.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although considerable advances in CRC treatment have been achieved, effective treatment improvement has hit a bottleneck. This study demonstrated that TYRO3 expression was aberrantly increased in CRC tissues with prognosis association. The prediction model of prognosis for CRC patients was constructed based on TYRO3 expression. The model suggested that the TYRO3 level is crucial to the final prediction results. We observed that knockdown TYRO3 expression could inhibit the proliferation and migration ability and reverse the drug resistance by constructing drug-resistant CRC cell lines. In vivo experiments also confirmed this conclusion. Thus, targeting TYRO3 combined with 5-Fu treatment could provide a better therapeutic effect. Additionally, TYRO3 could inhibit the EMT process by down-regulating ENO1, which may be achieved by interfering with energy metabolism in cancer cells. Therefore, the current study provides a theoretical basis for TYRO3 in drug-resistance of CRC cells and highlights a new strategy for CRC-targeted therapy.