Persistent acute kidney injury biomarkers: A systematic review and meta-analysis.

BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71-0.79),0.71 (95 % CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.

Multifunctional pressure and humidity sensor modulated by electrostatic interactions and hydrogen bonds for wearable health monitoring.

Breathing and urination, are vital physiological activities of the human body, continuous real-time monitoring of these physiological behaviors could offer timely feedback on an individual's health status. However, current monitoring techniques predominantly rely on cumbersome and intricate medical apparatuses, posing challenges in adapting to the diverse requirements of multi-scenario detection. Consequently, there is a growing interest in developing wearable devices capable of monitoring breathing and urination. In this work, we developed a multifunctional sensor integrating humidity and pressure sensing modes using a simple dip-coating process. By introducing sodium carboxymethyl cellulose and conductive polyaniline hybrid intercalation between MXene layers, a stable conductive network is established through hydrogen bonds and electrostatic interactions among materials. The overall electromechanical properties of the composites will be well improved. And, the effects of different conductive filler ratios and the number of dipping times on the construction of conductive networks are investigated. The multifunctional sensor exhibited improved sensing characteristics, including detecting pressures up to 532 kPa and a sensitivity of 19.58 kPa-1. Furthermore, it also demonstrates good humidity-sensing capabilities. Tests on volunteers demonstrated the potential in the detection of breathing and urination. In addition, the sensors are capable of transmitting Morse code. This interesting application will offer the possibility of normal communication for people with speech impairments. Given its utility and sustainability, the sensor has potential for applications in wearable health monitoring, intelligent life and telemedicine.

Differential expression of microRNAs in serum exosomes of obese and non-obese mice and analysis of their function.

OBJECTIVE: To extract exosomes from obese and non-obese mice, screen specifically expressed microRNAs by high-throughput sequencing and explore their roles. METHODS: An animal obesity model was constructed, and the successful construction of the obesity model was verified by HE staining, Western Blot and RT-qPCR. In addition, exosomes were extracted and verified by Western Blot. High-throughput sequencing was performed on the extracted serum exosomes to screen for differentially expressed microRNAs. fluorescence quantitative RT-PCR (RT-qPCR) was used to validate the differentially expressed miRNAs and explore their functions. RESULTS: 8 microRNAs were up-regulated and 11 microRNAs were down-regulated. mmu-miR-674-5p and X_28316 were significantly down-regulated and had the greatest impact on protein pathways. 8_13258 was significantly up-regulated and affected multiple protein pathways. GO enrichment analysis suggested that the differentially expressed microRNAs were mainly involved in the cleavage of microtubule activity, transferase activity/transferase pentameric acid. GO enrichment analysis suggested that differentially expressed microRNAs were mainly involved in the processes of cleavage microtubule activity, transferase activity/transfer pentamer, and threonine phosphatase/threonine kinase activity.KEGG pathway enrichment analysis showed that differentially expressed microRNAs were mainly involved in the processes of regulating the phosphorylation of TP53 activity, the G2/M DNA damage checkpoint, and the processing of the ends of DNA double-strand breaks. Protein interaction networks were enriched for Stat3, Fgr, Camk2b, Rac1, Asb6, and Ankfy1. Suggesting that they may be mediated by differential genes to participate in the process of insulin resistance. qRT-PCR results showed that the expression trend of mmu-miR-674-5p was consistent with the sequencing results. It suggests that it may be able to participate in the regulation of insulin resistance as a target gene. CONCLUSION: microRNAs were differentially expressed in serum exosomes of obese and non-obese mice and might be involved in the specific regulation of insulin resistance. mmu-miR-674-5p was differentially expressed significantly and the validation trend was consistent with it, suggesting that it might be able to participate in the regulation of insulin resistance as a target gene.

Flexible Strain Sensor Based on Nickel Microparticles/Carbon Black Microspheres/Polydimethylsiloxane Conductive Composites for Human Motion Detection.

Herein, we report a dual-functional flexible sensor (DFFS) using a magnetic conductive polymer composed of nickel (Ni), carbon black (CB), and polydimethylsiloxane (PDMS). The material selection for the DFFS utilizes the excellent elasticity of the PDMS matrix and the synergistic interaction between Ni and CB. The DFFS has a wide strain range of 0-170%, a high sensitivity of 74.13 (140-170%), and a low detection limit of 0.3% strain. The DFFS based on superior performance can accurately detect microstrain/microvibration, oncoming/contacting objects, and bicycle riding speed. Additionally, the DFFS can be used for comprehensive monitoring of human movements. Therefore, the DFFS of this work shows significant value for implementation in intelligent wearable devices and noncontact intelligent control.

Priority establishment of soil bacteria in rhizosphere limited the spread of tetracycline resistance genes from pig manure to soil-plant systems based on synthetic communities approach.

The spread of antibiotic resistance genes (ARGs) in agroecosystems through the application of animal manure is a global threat to human and environmental health. However, the adaptability and colonization ability of animal manure-derived bacteria determine the spread pathways of ARG in agroecosystems, which have rarely been studied. Here, we performed an invasion experiment by creating a synthetic communities (SynCom) with ten isolates from pig manure and followed its assembly during gnotobiotic cultivation of a soil-Arabidopsis thaliana (A. thaliana) system. We found that Firmicutes in the SynCom were efficiently filtered out in the rhizosphere, thereby limiting the entry of tetracycline resistance genes (TRGs) into the plant. However, Proteobacteria and Actinobacteria in the SynCom were able to establish in all compartments of the soil-plant system thereby spreading TRGs from manure to soil and plant. The presence of native soil bacteria prevented the establishment of manure-borne bacteria and effectively reduced the spread of TRGs. Achromobacter mucicolens and Pantoea septica were the main vectors for the entry of tetA into plants. Furthermore, doxycycline stress promoted the horizontal gene transfer (HGT) of the conjugative resistance plasmid RP4 within the SynCom in A. thaliana by upregulating the expression of HGT-related mRNAs. Therefore, this study provides evidence for the dissemination pathways of ARGs in agricultural systems through the invasion of manure-derived bacteria and HGT by conjugative resistance plasmids and demonstrates that the priority establishment of soil bacteria in the rhizosphere limited the spread of TRGs from pig manure to soil-plant systems.

Cochlear implantation in patients with Streptococcus suis meningitis: clinical characteristics and postoperative evaluation.

BACKGROUND: Hearing loss is a common sequala of Streptococcus suis (S. suis) meningitis, but few have addressed cochlear implantation (CI) candidates with S. suis meningitis. OBJECTIVES: To assess the clinical characteristics and CI postoperative outcomes in S. suis meningitis patients. MATERIAL AND METHODS: Eight S. suis meningitis patients underwent CI at Sun Yat-sen Memorial Hospital between 2020 and 2023. Control groups included (1) non-Suis meningitis patients (n = 12) and (2) non-meningitis patients (n = 35). Electrode impedances and neural response telemetry (NRT) thresholds were recorded at one month after surgery. The auditory performance-II (CAP) and speech intelligibility rating (SIR) were recorded at the last visit. RESULTS: CAP scores of S. suis meningitis patients were significantly lower than those of non-Suis meningitis and non-meningitis patients (p = .019; p<.001). And NRT thresholds of S. suis meningitis patients were higher than those of non-Suis meningitis and non-meningitis patients (p = .006; p = .027). CONCLUSIONS AND SIGNIFICANCE: It is recommended for S. suis meningitis CI candidates to undergo CI promptly after controlling infection, preferably within four to six weeks. CI users with S. suis meningitis tend to exhibit suboptimal hearing rehabilitation outcomes, possibly associated with the more severe damage on spiral ganglion cells after S. suis meningitis.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

Validation of the interaction between PRDX4 and TXNDC5 in gastric cancer and the significance of the PRDX4 gene in gastric cancer based on a data mining analysis.

Background: We successfully screened the important interacting protein peroxiredoxin 4 (PRDX4) of thioredoxin domain-containing protein 5 (TXNDC5) in gastric cancer. However, its specific molecular mechanism in gastric cancer remains unclear. This study aimed to verify the interaction between PRDX4 and TXNDC5 protein molecules in gastric cancer and analyze the expression and functional significance of PRDX4 in gastric cancer using bioinformatics methods. Methods: The interaction between TXNDC5 and PRDX4 was verified by the coimmunoprecipitation (co-IP) of the total protein of gastric cancer cells, and tissues with high expressions of TXNDC5. The Human Protein Atlas (HPA) database, UCSC Xena (University of California Santa Cruz xenabrowser) platform, the Kaplan-Meier Plotter platform, and the TIMER (Tumor IMmune Estimation Resource) platform were used to analyze the expression and subcellular localization of the PRDX4 molecule in normal human gastric tissue, the difference in expression between gastric cancer tissue and normal gastric tissue, the relationship between the expression of PRDX4 and survival, its functional significance in gastric cancer cells, and its effect on the tumor immune microenvironment (TIME). Results: The data analysis results showed that the expression of PRDX4 messenger RNA (mRNA) in the gastric cancer tissues was significantly higher than that in the normal tissues (P<0.05). PRDX4 could affect the occurrence and development of tumors by participating in the neutrophil degranulation signaling pathway to regulate tumor immunity. The expression level of PRDX4 has a certain relationship with the TIME; that is, it is mainly negatively correlated with the infiltration of B lymphocytes and CD4+ T lymphocytes (P<0.05). The expression level of PRDX4 was positively correlated with the expression of LILRB2 (leukocyte immunoglobulin-like receptor subfamily B member 2), and negatively correlated with BLTA (B and T lymphocyte attenuation factor) and VISTA (V-type immunoglobulin domain-containing suppressor of T cell activation) (P<0.05). Conclusions: There is an interaction between PRDX4 and TXNDC5 protein molecules in gastric cancer. PRDX4 gene expression is significantly up-regulated in gastric cancer. It may reduce the infiltration of B lymphocytes and CD4+ T lymphocytes and affect the expression of LILRB2, BLTA, and VISTA immune checkpoints, leading to anti-tumor immunosuppression.

Hybrid Ginseng-derived Extracellular Vesicles-Like Particles with Autologous Tumor Cell Membrane for Personalized Vaccination to Inhibit Tumor Recurrence and Metastasis.

Personalized cancer vaccines based on resected tumors from patients is promising to address tumor heterogeneity to inhibit tumor recurrence or metastasis. However, it remains challenge to elicit immune activation due to the weak immunogenicity of autologous tumor antigens. Here, a hybrid membrane cancer vaccine is successfully constructed by membrane fusion to enhance adaptive immune response and amplify personalized immunotherapy, which formed a codelivery system for autologous tumor antigens and immune adjuvants. Briefly, the functional hybrid vesicles (HM-NPs) are formed by hybridizing ginseng-derived extracellular vesicles-like particles (G-EVLPs) with the membrane originated from the resected autologous tumors. The introduction of G-EVLPs can enhance the phagocytosis of autologous tumor antigens by dendritic cells (DCs) and facilitate DCs maturation through TLR4, ultimately activating tumor-specific cytotoxic T lymphocytes (CTLs). HM-NPs can indeed strengthen specific immune responses to suppress tumors recurrence and metastasis including subcutaneous tumors and orthotopic tumors. Furthermore, a long-term immune protection can be obtained after vaccinating with HM-NPs, and prolonging the survival of animals. Overall, this personalized hybrid autologous tumor vaccine based on G-EVLPs provides the possibility of mitigating tumor recurrence and metastasis after surgery while maintaining good biocompatibility.

The influence of gender on the epidemiology of and outcome from sepsis associated acute kidney injury in ICU: a retrospective propensity-matched cohort study.

PURPOSES: The influence of gender on the epidemiology of and outcome from SA-AKI in ICU has not been fully clarified. Our aim is to elucidate these differences. METHODS: This study included adult patients with sepsis in MIMIC IV (V 2.2), and propensity matching analysis, cox regression and logistic regression were used to analyze gender differences in incidence, mortality and organ support rate. RESULTS: Of the 24,467 patients included in the cohort, 18,128 were retained after propensity score matching. In the matched cohort, the incidence of SA-AKI in males is higher than that in females (58.6% vs. 56.2%; P = 0.001).males were associated with a higher risk of SA-AKI (OR:1.07(1.01-1.14), P = 0.026;adjusted OR:1.07(1.01-1.14), P < 0.033).In SA-AKI patients, males were associated with a lower risk of ICU mortality(HR:0.803(0.721-0.893), P < 0.001;adjusted HR:0.836(0.746-0.937), P = 0.002) and in-hospital mortality(HR: 0.820(0.748-0.899), P < 0.001;adjusted HR:0.853(0.775-0.938), P = 0.003).there were no statistically significant differences between male and female patients in 1-year all-cause mortality (36.9% vs. 35.8%, P = 0.12), kidney replacement therapy rate (7.8% vs.7.4%, P = 0.547), mechanical ventilation rate 64.8% vs.63.9%, P = 0.369), and usage of vasoactive drugs (55.4% vs. 54.6%, P = 0.418). CONCLUSIONS: Gender may affect the incidence and outcomes of SA-AKI, further research is needed to fully understand the impact of gender on SA-AKI patients.

Intramuscular therapeutic doses of enrofloxacin affect microbial community structure but not the relative abundance of fluoroquinolones resistance genes in swine manure.

Livestock manure is a major source of veterinary antibiotics and antibiotic resistance genes (ARGs). Elucidation of the residual characteristics of ARGs in livestock manure following the administration of veterinary antibiotics is critical to assess their ecotoxicological effects and environmental contamination risks. Here, we investigated the effects of enrofloxacin (ENR), a fluoroquinolone antibiotic commonly used as a therapeutic drug in animal husbandry, on the characteristics of ARGs, mobile genetic elements, and microbial community structure in swine manure following its intramuscular administration for 3 days and a withdrawal period of 10 days. The results revealed the highest concentrations of ENR and ciprofloxacin (CIP) in swine manure at the end of the administration period, ENR concentrations in swine manure in groups L and H were 88.67 ± 45.46 and 219.75 ± 88.05 mg/kg DM, respectively. Approximately 15 fluoroquinolone resistance genes (FRGs) and 48 fluoroquinolone-related multidrug resistance genes (F-MRGs) were detected in swine manure; the relative abundance of the F-MRGs was considerably higher than that of the FRGs. On day 3, the relative abundance of qacA was significantly higher in group H than in group CK, and no significant differences in the relative abundance of other FRGs, F-MRGs, or MGEs were observed between the three groups on day 3 and day 13. The microbial community structure in swine manure was significantly altered on day 3, and the altered community structure was restored on day 13. The FRGs and F-MRGs with the highest relative abundance were qacA and adeF, respectively, and Clostridium and Lactobacillus were the dominant bacterial genera carrying these genes in swine manure. In summary, a single treatment of intramuscular ENR transiently increased antibiotic concentrations and altered the microbial community structure in swine manure; however, this treatment did not significantly affect the abundance of FRGs and F-MRGs.

Tactile corpuscle-inspired piezoresistive sensors based on (3-aminopropyl) triethoxysilane-enhanced CNPs/carboxylated MWCNTs/cellulosic fiber composites for textile electronics.

Recently, wearable electronic products and gadgets have developed quickly with the aim of catching up to or perhaps surpassing the ability of human skin to perceive information from the external world, such as pressure and strain. In this study, by first treating the cellulosic fiber (modal textile) substrate with (3-aminopropyl) triethoxysilane (APTES) and then covering it with conductive nanocomposites, a bionic corpuscle layer is produced. The sandwich structure of tactile corpuscle-inspired bionic (TCB) piezoresistive sensors created with the layer-by-layer (LBL) technology consists of a pressure-sensitive module (a bionic corpuscle), interdigital electrodes (a bionic sensory nerve), and a PU membrane (a bionic epidermis). The synergistic mechanism of hydrogen bond and coupling agent helps to improve the adhesive properties of conductive materials, and thus improve the pressure sensitive properties. The TCB sensor possesses favorable sensitivity (1.0005 kPa-1), a wide linear sensing range (1700 kPa), and a rapid response time (40 ms). The sensor is expected to be applied in a wide range of possible applications including human movement tracking, wearable detection system, and textile electronics.

Improved Photodynamic Therapy Based on Glutaminase Blockage via Tumor Membrane Coated CB-839/IR-780 Nanoparticles.

Photodynamic therapy (PDT) has promising applications. However, the lethal function of reactive oxygen species (ROS) produced during PDT is typically limited. This restriction is induced by oxygen shortage in the tumor microenvironment due to tumor cell hypermetabolism and reductive chemicals overexpression in tumor tissues. Glutamine (Gln) metabolism is crucial for malignancy development and is closely associated with redox. Herein, a novel nanoparticle (NP) named IRCB@M is constructed to boost PDT through dual effects. This NP simultaneously blocks aerobic respiration and inhibits cellular reduced substances by blocking the Gln metabolic pathway. Within the nanocomplex, a photosensitizer (IR-780) and a glutaminase inhibitor (CB-839) are self-assembled and then encapsulated by cancer cell membranes for homologous targeting. The Gln metabolism intervention relieves hypoxia and decreases the levels of nicotinamide adenine dinucleotide phosphate (NADPH) as well as reduced glutathione (GSH) in vitro and in vivo, which are the dual amplification effects on the IR-780-mediated lethal PDT. The antitumor effects against gastric cancer are ultimately evoked in vivo, thus offering a novel concept for enhancing PDT and other ROS-dependent therapeutic approaches.

Using Fe/H2O2-modified biochar to realize field-scale Sb/As stabilization and soil structure improvement in an Sb smelting site.

Antimony (Sb) and arsenic (As) released from the Sb smelting activities pose a major environmental risk and ecological degradation in Sb smelting sites. Here the effects of Fe/H2O2 modified biochar (Fe@H2O2-BC) on the synchronous stabilization of Sb/As and the improvement of soil structure in a typical Sb smelting site in Southern China based on a 1-year field experiment were studied. Application of ≥1 % (w/w) Fe@H2O2-BC could stably decrease the leaching concentrations of Sb and As of the polluted soils to Environmental quality standards for surface water Chinese Level III (GB3838-2002). Compared to the untreated soils, the stabilization efficiency of soil Sb and As treated by Fe@H2O2-BC reached 90.7 % ~ 95.7 % and 89.6 % ~ 90.8 %, respectively. The residue fractions of Sb/As in the soils increased obviously, and the bio-availability of Sb/As decreased by 65.0-95.6 % and 91.1-96.0 %, respectively. Moreover, Fe@H2O2-BC addition elevated soil organic carbon content, increased soil porosity, and improved water retention capacity, indicating the positive effects on soil structure and functions. Advanced mineral identification and characterization systems showed that Sb/As usually occurred in Fe-bearing minerals and stabilized by surface complexation and co-precipitation. The findings demonstrated that 1 % (w/w) Fe@H2O2-BC was appropriate to Sb/As stabilization and soil function recovery following field conditions, which provided potential application for ecological restoration in Sb smelting sites.

Dynamic Compressive Properties and Failure Mechanism of the Laser Powder Bed Fusion of Submicro-LaB6 Reinforced Ti-Based Composites.

In this study, lanthanum hexaboride (LaB6) particle-reinforced titanium matrix composites (PRTMCs, TC4/LaB6) were successfully manufactured using the laser powder bed fusion (LPBF) process. Thereafter, the effect of the mass fraction of LaB6 on the microstructure and the dynamic compressive properties was investigated. The results show that the addition of LaB6 leads to significant grain refinement. Moreover, the general trend of grain size reveals a concave bend as the fraction increases from 0.2% to 1.0%. Furthermore, the texture intensity of prior ß grains and α grains was found to be weakened in the composites. It was also observed that the TC4/LaB6 have higher quasi-static and dynamic compressive strengths but lower fracture strain when compared with the as-built TC4. The sample with 0.5 wt.% LaB6 was found to have the best strength-toughness synergy among the three groups of composites due to having the smallest grain size. Furthermore, the fracture mode of TC4/LaB6 was found to change from the fracture under the combined action of brittle and ductility to the cleavage fracture. This study was able to provide a theoretical basis for an in-depth understanding of the compressive properties of additive manufacturing of PRTMCs under high-speed loading conditions.

Flexible Capacitive Pressure Sensor with High Sensitivity and Wide Range Based on a Cheetah Leg Structure via 3D Printing.

Flexible pressure sensors can be used in human-computer interaction and wearable electronic devices, but one main challenge is to fabricate capacitive sensors with a wide pressure range and high sensitivity. Here, we designed a capacitive pressure sensor based on a bionic cheetah leg microstructure, validated the benefits of the bionic microstructure design, and optimized the structural feature parameters using 3D printing technology. The pressure sensor inspired by the cheetah leg shape has a high sensitivity (0.75 kPa-1), a wide linear sensing range (0-280 kPa), a fast response time of roughly 80 ms, and outstanding durability (24,000 cycles). Furthermore, the sensor can recognize a finger-operated mouse, monitor human motion, and transmit Morse code information. This work demonstrates that bionic capacitive pressure sensors hold considerable promise for use in wearable devices.

HGNNLDA: Predicting lncRNA-Drug Sensitivity Associations via a Dual Channel Hypergraph Neural Network.

Drug sensitivity is critical for enabling personalized treatment. Many studies have shown that long non-coding RNAs (lncRNAs) are closely related to drug sensitivity because lncRNAs can regulate genes related to drug sensitivity to affect drug efficacy. Exploring lncRNA-drug sensitivity associations has important implications for drug development and disease treatment. However, identifying lncRNA-drug sensitivity associations based on traditional biological approaches is small-scale and time-consuming. In this work, we develop a dual-channel hypergraph neural network-based method named HGNNLDA to infer unknown lncRNA-drug sensitivity associations. To our best knowledge, HGNNLDA is the first computational framework to predict lncRNA-drug sensitivity associations. HGNNLDA applies the hypergraph neural network to obtain high-order neighbor information on the lncRNA hypergraph and the drug hypergraph, respectively, and utilizes a joint update mechanism to generate lncRNA embeddings and drug embeddings. In traditional graphs, an edge contains only two nodes. However, hyperedges in hypergraphs can contain any number of nodes and hypergraphs can well describe the higher-order connectivity of the lncRNA-drug bipartite graphs. The comprehensive experimental results show that HGNNLDA significantly outperforms the other six state-of-the-art models. Case studies on two drugs further illustrate that HGNNLDA is an effective tool to predict lncRNA-drug sensitivity associations.

Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.