miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Label-free and ultrasensitive detection of environmental lead ions based on spatially localized DNA nanomachines driven by hyperbranched hybridization chain reaction.

A label-free fluorescent sensing strategy for the rapid and highly sensitive detection of Pb2+ was developed by integrating Pb2+ DNAzyme-specific cleavage activity and a tetrahedral DNA nanostructure (TDN)-enhanced hyperbranched hybridization chain reaction (hHCR). This strategy provides accelerated reaction rates because of the highly effective collision probability and enriched local concentrations from the spatial confinement of the TDN, thus showing a higher detection sensitivity and a more rapid detection process. Moreover, a hairpin probe based on a G-triplex instead of a G-quadruplex or chemical modification makes hybridization chain reaction more controlled and flexible, greatly improving signal amplification capacities and eliminating labeled DNA probes. The enhanced reaction rates and improved signal amplification efficiency endowed the biosensors with high sensitivity and a rapid response. The label-free detection of Pb2+ based on G-triplex combined with thioflavin T can be achieved with a detection limit as low as 1.8 pM in 25 min. The proposed Pb2+-sensing platform was also demonstrated to be applicable for Pb2+ detection in tap water, river water, shrimp, rice, and soil samples, thus showing great potential for food safety and environmental monitoring.

Applications of Biosensors in Bladder Cancer.

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

Association between frailty index based on laboratory tests and all-cause mortality in critically ill patients with heart failure.

BACKGROUND: The frailty index based on laboratory tests (FI-lab) can identify individuals at increased risk for adverse health outcomes. The association between the FI-lab and all-cause mortality in patients with heart failure (HF) in the intensive care unit (ICU) remains unknown. This study aimed to determine the correlation between FI-lab and all-cause mortality to evaluate the impact of FI-lab on the prognosis of critically ill patients with HF. METHODS: This retrospective observational study utilized data extracted from the Medical Information Mart for Intensive Care IV database. The FI-lab, which consists of 33 laboratory tests, was constructed. Patients were then grouped into quartiles (Q1-Q4) based on their FI-lab scores. Kaplan-Meier analysis was used to compare all-cause mortality among the four groups. A Cox proportional hazard analysis was conducted to examine the association between the FI-lab score and all-cause mortality. The incremental predictive value of adding FI-lab to classical disease severity scores was assessed using Harrell's C statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI). RESULTS: Among 3021 patients, 838 (27.74%) died within 28 days, and 1400 (46.34%) died within a 360 day follow-up period. Kaplan-Meier analysis indicated that patients with higher FI-lab scores had significantly higher risks of all-cause mortality (log-rank P < 0.001). Multivariable Cox regression suggested that FI-lab, evaluated as a continuous variable (for each 0.01 increase), was associated with increased 28 day mortality [hazard ratio (HR) 1.02, 95% confidence interval (CI) (1.01-1.03), P < 0.001] and 360 day mortality [HR 1.02, 95% CI (1.01-1.02), P < 0.001]. When assessed in quartiles, the 28 day mortality risk [HR 1.66, 95% CI (1.28-2.15), P < 0.001] and 360 day mortality risk [HR 1.48, 95% CI (1.23-1.8), P < 0.001] were significantly higher for FI-lab Q4 compared with FI-lab Q1. FI-lab significantly improved the predictive capability of classical disease severity scores for 28 and 360 day mortality. CONCLUSIONS: In ICU patients diagnosed with HF, the FI-lab is a potent predictor of short-term and long-term mortality in critically ill patients with HF. The active use of FI-lab to identify high-risk groups among critically ill HF patients and initiate timely interventions may have significant value in improving the prognosis of critically ill patients with HF.

Mauritone A, a new polyketide from a fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532.

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

Astragalusliuaiminii, a new species of Astragalus (Fabaceae) from Xinjiang, China.

A new species, Astragalusliuaiminii Z. Z. Yang & Q. R. Liu (Fabaceae), is described and illustrated from Xinjiang Province, China. The new species is close to A.wenquanensis S. B. Ho, but differs from the latter by leaves having a single leaflet (vs. 3-5 leaflets), and inflorescences with 1-2 flowers (vs. inflorescences with 5-7 flowers). It is also similar to A.monophyllus Maxim in leaf shape, but differs by its calyx expanding to become saccate and totally enveloping the pod (vs. calyx tubular, and ruptured by pod after flowering).

Interfacial Hydrogen-Bond Interactions Driven Assembly toward Polychromatic Copper Nanoclusters.

Constructing versatile metal nanoclusters (NCs) assemblies through noncovalent weak interactions between inter-ligands is a long-standing challenge in interfacial chemistry, while compelling interfacial hydrogen-bond-driven metal NCs assemblies remain unexplored so far. Here, the study reports an amination-ligand o-phenylenediamine-coordinated copper NCs (CuNCs), demonstrating the impact of interfacial hydrogen-bonds (IHBs) motifs on the luminescent behaviors of metal NCs as the alteration of protic solvent. Experimental results supported by theoretical calculation unveil that the flexibility of interfacial ligand and the distance of cuprophilic CuI···CuI interaction between intra-/inter-NCs can be tailored by manipulating the cooperation between the diverse IHBs motifs reconstruction, therewith the IHBs-modulated fundamental structure-property relationships are established. Importantly, by utilizing the IHBs-mediated optical polychromatism of aminated CuNCs, portable visualization of humidity sensing test-strips with fast response is successfully manufactured. This work not only provides further insights into exploring the interfacial chemistry of NCs based on inter-ligands hydrogen-bond interactions, but also offers a new opportunity to expand the practical application for optical sensing of metal NCs.

The Role of the Intestinal Flora and Its Derivatives in Neurocognitive Disorders: A Narrative Review from Surgical Perspective.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Exploring the ecological security evaluation of water resources in the Yangtze River Basin under the background of ecological sustainable development.

The Yangtze River (hereafter referred to as the YZR), the largest river in China, is of paramount importance for ensuring water resource security. The Yangtze River Basin (hereafter referred to as the YRB) is one of the most densely populated areas in China, and complex human activities have a significant impact on the ecological security of water resources. Therefore, this paper employs theories related to ecological population evolution and the Driving Force-Pressure-State-Impact-Response (DPSIR) model to construct an indicator system for the ecological security of water resources in the YRB. The report evaluates the ecological security status of water resources in each province of the YRB from 2010 to 2019, clarifies the development trend of its water resource ecological security, and proposes corresponding strategies for regional ecological security and coordinated economic development. According to the results of the ecological population evolution competition model, the overall indicator of the ecological security of water resources in the YRB continues to improve, with the safety level increasing annually. Maintaining sound management of water resources in the YRB is crucial for sustainable socioeconomic development. To further promote the ecological security of water resources in the YRB and the coordinated development of the regional economy, this paper proposes policy suggestions such as promoting the continuous advancement of sustainable development projects, actively adjusting industrial structure, continuously enhancing public environmental awareness, and actively participating in international ecological construction and seeking cooperation among multiple departments.

Which one is the best in treating deep venous thrombosis -- percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?

OBJECTIVE: To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both. METHODS: One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up. RESULTS: Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006). CONCLUSION: Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.

Environmental remediation potential of a pioneer plant (Miscanthus sp.) from abandoned mine into biochar: Heavy metal stabilization and environmental application.

Pyrolysis stands out as an effective method for the disposal of phytoremediation residues in abandoned mines, yielding a valuable by-product, biochar. However, the environmental application of biochar derived from such residues is limited by the potential environmental risks of heavy metals. Herein, Miscanthus sp. residues from abandoned mines were pyrolyzed into biochars at varied pyrolysis temperatures (300-700 °C) to facilitate the safe reuse of phytoremediation residues. The results showed that pyrolysis significantly stabilizes heavy metals in biomass, with Cd exhibiting the most notable stabilization effect. Acid-soluble/exchangeable and reducible fractions of Cd decreased significantly from 69.91 % to 2.52 %, and oxidizable and residue fractions increased approximately 3.24 times at 700 °C. The environmental risk assessment indicated that biochar pyrolyzed over 500 °C pose lower environmental risk (RI < 30), making them optimal for the safe utilization of phytoremediation residues. Additionally, adsorption experiments suggested that biochars prepared at higher temperature (500-700 °C) exhibit superior adsorption capacity, attributed to alkalinity and precipitation effect. This study highlights that biochars produced by pyrolyzing Miscanthus sp. from abandoned mines above 500 °C hold promise for environmental remediation, offering novel insight into the reutilization of metal-rich biomass.

Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

Rab11b promotes M1-like macrophage polarization by restraining autophagic degradation of NLRP3 in alcohol-associated liver disease.

Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

Ambient Moisture-Driven Self-Powered Iontophoresis Patch for Enhanced Transdermal Drug Delivery.

Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self-powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist-electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open-circuit voltage of 0.80 V and a short-circuit current of 11.65 µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.

NPh3-Mediated WO3-Photocatalyzed Semiheterogeneous Hydroxylation of Aryl and Alkyl Boronic Acids.

With an inexpensive and commercially available WO3 semiconductor as the heterogeneous photocatalyst, a catalytic amount of NPh3 as the single-electron donor, and ambient air as the single-electron acceptor and oxygen source, the semiheterogeneous photocatalytic hydroxylation of alkyl and aryl boronic acids was developed. A broad range of hydroxylated compounds can be obtained in excellent yields.

Portable SERS biosensor based on aptamer-assisted catalytic hairpin assembly signal amplification for ultrasensitive detection of Staphylococcus aureus.

Bacteria infections pose a serious threat to public health, and it is urgent to develop facile and accurate detection methods. To meet the important need, a potable and high-sensitive surface enhanced Raman scattering (SERS) biosensor based on aptamer recognition and catalytic hairpin assembly (CHA) signal amplification was proposed for point-of-care detection of Staphylococcus aureus (S. aureus). The SERS biosensor contains three parts: recognition probes, SERS sensing chip, and SERS tags. The feasibility of the strategy was verified by gel electrophoresis, and the one-step test route was optimized. The bacteria SERS biosensor has a good linear relationship ranging from 10 to 107 CFU mL-1 with high sensitivity low to 5 CFU mL-1, and shows excellent specificity, uniformity, and repeatability on S. aureus identification and enumeration, which can distinguish S. aureus from other bacteria. The SERS biosensor shows a good recovery rate (95.73 %-109.65 %) for testing S. aureus spiked in milk, and has good practicability for detecting S. aureus infected mouse wound, which provides a facile and reliable approach for detection of trace bacteria in the real samples.

A hypothalamic-amygdala circuit underlying sexually dimorphic aggression.

Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice. Although the VMHvl innervates the pSI unidirectionally through both excitatory and inhibitory connections, it is the excitatory VMHvl-pSI projections that are strengthened in males to promote aggression, whereas the inhibitory connections that reduce aggressive behavior are strengthened in females. Consequently, the convergent hypothalamic input onto the pSI leads to heightened pSI activity in males, resulting in male-biased aggression. Our findings reveal a sexually distinct excitation-inhibition balance of a hypothalamic-amygdala circuit that underlies sexually dimorphic aggression.