In Situ Collection and SERS Detection of Nitrite in Exhalations on Facemasks Based on Wettability Differences.

As one of the common carriers of biological information, along with human urine specimens and blood, exhaled breath condensate (EBC) carries reliable and rich information about the body's metabolism to track human physiological normal/abnormal states and environmental exposures. What is more, EBC has gained extensive attention because of the convenient and nondestructive sampling. Facemasks, which act as a physical filter barrier between human exhaled breath and inhaled substances from the external environment, are safe, noninvasive, and economic devices for direct sampling of human exhaled breath and inhaled substances. Inspired by the ability of fog collection of Namib desert beetle, a strategy for in situ collecting and detecting EBC with surface-enhanced Raman scattering is illustrated. Based on the intrinsic and unique wettability differences between the squares and the surrounding area of the pattern on facemasks, the hydrophilic squares can capture exhaled droplets and spontaneously enrich the analytes and silver nanocubes (AgNCs), resulting in good repeatability in situ detection. Using R6G as the probe molecule, the minimal detectable concentration can reach as low as 10-16 M, and the relative standard deviation is less than 7%. This proves that this strategy can achieve high detection sensitivity and high detection repeatability. Meanwhile, this strategy is applicable for portable nitrite analysis in EBC and may provide an inspiration for monitoring other biomarkers in EBC.

Hybrid Membrane-Camouflaged Biomimetic Immunomodulatory Nanoturrets with Sequential Multidrug Release for Potentiating T Cell-Mediated Anticancer Immunity.

Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and immunologically "cold" tumors severely compromise its immunotherapeutic outcomes. As such, the reversal of the immunosuppressive tumor microenvironment (TME) has been the premise for improving the effectiveness of AA-based immunotherapy, which hinges upon advanced AA delivery and amplified immune-activating strategies. Herein, a novel Escherichia coli (E. coli) outer membrane vesicle (OMV)-red blood cell (RBC) hybrid membrane (ERm)-camouflaged immunomodulatory nanoturret is meticulously designed based on gating of an AA-immobilized metal-organic framework (MOF) onto bortezomib (BTZ)-loaded magnesium-doped mesoporous silica (MMS) nanovehicles, which can realize immune landscape remodeling by chemotherapy-assisted ascorbate-mediated immunotherapy (CAMIT). Once reaching the acidic TME, the acidity-sensitive MOF gatekeeper and MMS core within the nanoturret undergo stepwise degradation, allowing for tumor-selective sequential release of AA and BTZ. The released BTZ can evoke robust immunogenic cell death (ICD), synergistically promote dendritic cell (DC) maturation in combination with OMV, and ultimately increase T cell tumor infiltration together with Mg2+. The army of T cells is further activated by AA, exhibiting remarkable antitumor and antimetastasis performance. Moreover, the CD8-deficient mice model discloses the T cell-dependent immune mechanism of the AA-based CAMIT strategy. In addition to providing a multifunctional biomimetic hybrid nanovehicle, this study is also anticipated to establish a new immunomodulatory fortification strategy based on the multicomponent-driven nanoturret for highly efficient T cell-activation-enhanced synergistic AA immunotherapy.

Characteristics and risk assessment of potentially toxic elements pollution in river water and sediment in typical gold mining areas of Northwest China.

To assess the concentration characteristics and ecological risks of potential toxic elements (PTEs) in water and sediment, 17 water samples and 17 sediment samples were collected in the Xiyu River to analyze the content of Cr, Ni, As, Cu, Zn, Pb, Cd and Hg, and the environmental risks of PTEs was evaluated by single-factor pollution index, Nemerow comprehensive pollution index, potential ecological risk, and human health risk assessment. The results indicated that Hg in water and Pb, Cu, Cd in sediments exceeded the corresponding environmental quality standards. In the gold mining factories distribution river section (X8-X10), there was a significant increase in PTEs in water and sediments, indicating that the arbitrary discharge of tailings during gold mining flotation is the main cause of PTEs pollution. The increase in PTEs concentration at the end of the Xiyu River may be related to the increased sedimentation rate, caused by the slowing of the riverbed, and the active chemical reactions at the estuary. The single-factor pollution index and Nemerow pollution index indicated that the river water was severely polluted by Hg. Potential ecological risk index indicated that the risk of Hg in sediments was extremely high, the risk of Cd was high, and the risk of Pb and Cu was moderate. The human health risk assessment indicated that As in water at point X10 and Hg in water at point X9 may pose non-carcinogenic risk to children through ingestion, and As at X8-X10 and Cd at X14 may pose carcinogenic risk to adults through ingestion. The average HQingestion value of Pb in sediments was 1.96, indicating that the ingestion of the sediments may poses a non-carcinogenic risk to children, As in the sediments at X8-X10 and X15-X17 may pose non-carcinogenic risk to children through ingestion.

Serum magnesium and calcium were inversely associated with hemoglobin glycation index and triglyceride-glucose index in adults with coronary artery disease.

Little is known about the associations of magnesium (Mg) and calcium (Ca) with hemoglobin glycation index (HGI) and triglyceride-glucose index (TyG) in adults. In this study, we examined the associations of serum Mg and Ca with HGI and TyG in adults with coronary artery disease (CAD). This hospital-based cross-sectional study included 10757 CAD patients with a mean age of 61.6 years. Serum concentrations of Mg and Ca were measured in clinical laboratory. Overall, serum Mg and Ca were inversely associated with HGI and TyG. In multivariable analyses, Mg and Ca were inversely associated with HGI (MgQ4 vs. Q3: -0.601 vs. -0.528; CaQ4 vs. Q1: -0.769 vs. -0.645). In terms of TyG, inverse associations of serum Mg and Ca with TyG were observed. The corresponding TyG values were 9.054 (vs. 9.099) for Mg and 9.068 (vs. 9.171) for Ca in the fourth quartile compared with the first quartile. Moreover, Mg, Ca or Mg/Ca ratio were also inversely associated with HbA1c and FBG. In path analysis, no mediating effects of obesity on "serum Mg (or Ca)- HGI (or TyG)" associations were observed. Generally, our study identified the inverse associations of the serum Mg and Ca levels with HGI and TyG in adults with CAD. Large sample longitudinal study, and particularly randomized controlled trials, are warranted to validate our findings and overcome the limitations of cross-sectional studies.

Vividness of visual imagery is associated with the effect of relaxation response meditation training in elderly people with nonorganic insomnia: A randomized, double-blind, multi-center clinical trial.

BACKGROUND: This study aims to explore the efficacy of Relaxation Response Meditation Training (RRMT) on elderly individuals with different levels of vividness of visual imagery. METHODS: In this randomized controlled, double-blind, multi-center clinical trial, we recruited a total of 136 elderly individuals who were over 60 years with nonorganic sleep disorders to participate in a 4-week RRMT intervention from October 2020 to October 2022. The intervention occurred twice a week, totaling eight times. These individuals were divided into high and low groups based on the vividness of visual imagery, and then randomly assigned to either the control or intervention groups, as follows: low-visualizers intervention group (LI group); low-visualizers control group (LC group); high-visualizers intervention group (HI group); high-visualizers control group (HC group). Their social and psychological parameters were assessed before and after the intervention by the Pittsburgh Sleep Quality Index (PSQI), the Revised Piper's fatigue scale (RPFS), General well-being scale (GWB), and Satisfaction rating. The alpha waves of patients were also collected through electroencephalogram to assess their level of relaxation. RESULTS: Compared to the LI group, the HI group had a greater reduction rate in the PSQI score [25.2 % (18.8 % to 31.7 %), P < 0∙001], shorter sleep latency (P = 0.001), lower frequency of sleep medication (P < 0.001), lower PSQI scores (P < 0.001), and higher GWB scores (P < 0.001). There were significant differences in all indicators in the HI group vs. HC group and in the LI group vs. LC group. In the first five relaxation training sessions, there was no statistically significant difference in the proportion of α waves between the LI group and the LC group; however, from the sixth session onward, we observed a statistically significant difference (t = 2.86, P = 0.019)，while The HI group and HC group showing significant differences in the first relaxation training session (t = 4.464, P < 0.001). There was a statistically significant difference in subjective satisfaction between the intervention group and the control group (x2 = 49.605, P < 0.001). CONCLUSION: In this study, we found that most elderly people benefitted from RRMT regardless of their vividness of visual imagery. However, low-visualizers experienced slower and less effective results, so these patients may benefit more from alternative approaches.

Adverse childhood experiences and self-esteem among adolescents: The role of social capital and gender.

INTRODUCTION: Adverse childhood experiences have long-lasting effects on the self-esteem of adolescents. However, the extrinsic mechanism linking them to self-esteem, which is more modifiable, has rarely been examined. Therefore, this study examined the mediating roles of family, school, and peer social capital and the moderating role of gender in the association between adverse childhood experiences and adolescent self-esteem. METHODS: This study involved a cross-sectional survey of first- and second-grade students in the only high school in Wusu, Xinjiang Uygur Autonomous Region, China. Data were collected in May 2023. A sample of 2539 students (M = 16.84 years old; 55.65% female) was included. The measurement models of family, school, and peer social capital were constructed using confirmatory factor analysis. The mediating roles of the three types of social capital and the moderating role of gender were examined using mediation analysis and multiple-group analysis, respectively. RESULTS: Family, school, and peer social capital significantly mediated the relationship between adverse childhood experiences and adolescent self-esteem, and family social capital played the strongest role. Gender significantly moderated the direct effect of adverse childhood experiences on self-esteem. The direct effect was significant only among girls. CONCLUSIONS: This study underscores the protective role of social capital for self-esteem among adolescents in Northwestern China and similar areas with relatively limited social services. Comprehensive interventions promoting social capital, especially family social capital, should be conducted to enhance self-esteem among adolescents.

Relationship Between Coronary Artery Revascularization and Postoperative Delirium: Progress and Perspectives.

Brain dysfunction resulting from damage to the heart-brain link leads to a decline in cognitive function. This, in turn, gives rise to the clinical symptom of perioperative delirium in patients undergoing coronary artery revascularization. Those affected are provided symptomatic treatment, but many do not recover fully. Thus, medium- and long-term mortality and adverse event rates remain relatively high in patients with perioperative delirium. Despite the relatively high incidence of perioperative delirium in patients undergoing coronary artery revascularization, it has not been systematically investigated. Inflammation, vascular damage, neuronal damage, and embolism are all involved in the injury process. Here, we discuss the incidence rate, pathological mechanisms, and prognosis of delirium after coronary artery revascularization. We also discuss in detail the risk factors for delirium after coronary artery revascularization, such as anxiety, depression, mode of operation, and drug use. We hope that prevention, early diagnosis, assessment, and potential treatment can be achieved by cardiologists to improve patient prognosis.

A Flexible and Mechanical Robust All-Solid-State Polymer Electrolyte with Microphase Separated Structure for Lithium-Ion Battery.

Polyethylene oxide (PEO)-based electrolytes are the most widely used solid polymer electrolyte (SPE) due to their high safety, excellent ability to dissociate lithium salts, low cost, and ease of preparation. However, low ionic conductivity and narrow electrochemical stability window limit their potential for further development. "Polymer-in-salt" electrolytes exhibit superior electrochemical performance; however, the high lithium salt concentration makes the SPE mechanically fragile when facing lithium dendrites. Therefore, preparing an SPE that can withstand a high concentration of lithium salt while still maintaining good mechanical properties has become a valuable challenge. In this study, a macroscopically homogeneous but nanoscopically phase-separated polymer matrix was designed as an electrolyte that can withstand a high concentration of lithium salt while retaining good mechanical properties, and this study investigated changes in the Li+ solvation structure within the electrolyte and analyzed the reasons for the simultaneous achievement of good ionic conductivity (1.02 × 10-3 S cm-1 at 60 °C) and mechanical properties (7 MPa at room temperature). The formation of large ion clusters at the phase interface and selective enrichment of lithium salt in specific regions are found to play crucial roles, and the critical current density (CCD) can reach a value of 2.2 mA cm-2. This work demonstrates a promising design approach for polymer electrolytes that achieves an optimal balance between SPE conductivity and mechanical properties through microstructure control.

Revisiting decade-old questions in proanthocyanidin biosynthesis: current understanding and new challenges.

Proanthocyanidins (PAs), one of the most abundant natural polymers found in plants, are gaining increasing attention because of their beneficial effects for agriculture and human health. The study of PA biosynthesis has been active for decades, and progress has been drastically accelerated since the discovery of key enzymes such as Anthocyanidin Reductase (ANR), Leucoanthocyanidin Reductase (LAR), and key transcription factors such as Transparent Testa 2 (TT2) and Transparent Testa 8 (TT8) in the early 2000s. Scientists raised some compelling questions regarding PA biosynthesis about two decades ago in the hope that addressing these questions would lead to an enhanced understanding of PA biosynthesis in plants. These questions focus on the nature of starter and extension units for PA biosynthesis, the stereochemistry of PA monomers and intermediates, and how and where the polymerization or condensation steps work subcellularly. Here, I revisit these long-standing questions and provide an update on progress made toward answering them. Because of advanced technologies in genomics, bioinformatics and metabolomics, we now have a much-improved understanding of functionalities of key enzymes and identities of key intermediates in the PA biosynthesis and polymerization pathway. Still, several questions, particularly the ones related to intracellular PA transportation and deposition, as well as enzyme subcellular localization, largely remain to be explored. Our increasing understanding of PA biosynthesis in various plant species has led to a new set of compelling open questions, suggesting future research directions to gain a more comprehensive understanding of PA biosynthesis.

Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

The dynamics of nocturnal sap flow components of a typical revegetation shrub species on the semiarid Loess Plateau, China.

Introduction: The components of nighttime sap flux (En), which include transpiration (Qn) and stem water recharge (Rn), play important roles in water balance and drought adaptation in plant communities in water-limited regions. However, the quantitative and controlling factors of En components are unclear. Methods: This study used the heat balance method to measure sap flow density in Vitex negundo on the Loess Plateau for a normal precipitation year (2021) and a wetter year (2022). Results: The results showed that the mean values were 1.04 and 2.34 g h-1 cm-2 for Qn, 0.19 and 0.45 g h-1 cm-2 for Rn in 2021 and 2022, respectively, and both variables were greater in the wetter year. The mean contributions of Qn to En were 79.76% and 83.91% in 2021 and 2022, respectively, indicating that the En was mostly used for Qn. Although the vapor pressure deficit (VPD), air temperature (Ta) and soil water content (SWC) were significantly correlated with Qn and Rn on an hourly time scale, they explained a small fraction of the variance in Qn on a daily time scale. The main driving factor was SWC between 40-200 cm on a monthly time scale for the Qn and Rn variations. Rn was little affected by meteorological and SWC factors on a daily scale. During the diurnal course, Qn and Rn initially both declined after sundown because of decreasing VPD and Ta, and Qn was significantly greater than Rn, whereas the two variables increased when VPD was nearly zero and Ta decreased, and Rn was greater than Qn. Discussion: These results provided a new understanding of ecophysiological responses and adaptation of V. negundo plantations to increasing drought severity and duration under climate changes.

CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits esophageal squamous cell carcinoma progression by promoting USP14-mediated de-ubiquitination of PIK3IP1.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. The PI3K/AKT signaling pathway plays a key role in the development of ESCC. CircRNAs have been reported to be involved in the regulation of the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC. METHODS: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC-MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A. RESULTS: We found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S-S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo. CONCLUSION: The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents.

Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation.

Ricin toxin (RT) is highly cytotoxic and can release a considerable amount of pro-inflammatory factors due to depurination, causing excessive inflammation that may aggravate the harm to the body. Pyroptosis, a type of gasdermin-mediated cell death, is a contributor to the exacerbation of inflammation. Accumulating evidence indicate that pyroptosis plays a significant role in the pathogen infection and tissue injury, suggesting a potential correlation between pyroptosis and RT-induced inflammation. Here, we aim to demonstrate this correlation and explore its molecular mechanisms. Results showed that RT triggers mouse alveolar macrophage MH-S cells pyroptosis by activating caspase-3 and cleaving Gasgermin E (GSDME). In contrast, inhibition of caspase-3 with Z-DEVD-FMK (inhibitor of caspase-3) or knockdown of GSDME attenuates this process, suggesting the essential role of caspase-3/GSDME-mediated pyroptosis in contributing to RT-induced inflammation. Collectively, our study enhances our understanding of a novel mechanism of ricin cytotoxicity, which may emerge as a potential target in immunotherapy to control the RT-induced inflammation.

Label-Free Single Microparticles and Cell Aggregates Sorting in Continuous Cell-Based Manufacturing.

There is a paradigm shift in biomanufacturing toward continuous bioprocessing but cell-based manufacturing using adherent and suspension cultures, including microcarriers, hydrogel microparticles, and 3D cell aggregates, remains challenging due to the lack of efficient in-line bioprocess monitoring and cell harvesting tools. Herein, a novel label-free microfluidic platform for high throughput (≈50 particles/sec) impedance bioanalysis of biomass, cell viability, and stem cell differentiation at single particle resolution is reported. The device is integrated with a real-time piezo-actuated particle sorter based on user-defined multi-frequency impedance signatures. Biomass profiling of Cytodex-3 microcarriers seeded with adipose-derived mesenchymal stem cells (ADSCs) is first performed to sort well-seeded or confluent microcarriers for downstream culture or harvesting, respectively. Next, impedance-based isolation of microcarriers with osteogenic differentiated ADSCs is demonstrated, which is validated with a twofold increase of calcium content in sorted ADSCs. Impedance profiling of heterogenous ADSCs-encapsulated hydrogel (alginate) microparticles and 3D ADSC aggregate mixtures is also performed to sort particles with high biomass and cell viability to improve cell quality. Overall, the scalable microfluidic platform technology enables in-line sample processing from bioreactors directly and automated analysis of cell quality attributes to maximize cell yield and improve the control of cell quality in continuous cell-based manufacturing.

Could nerve transplantation be the future of this field: a bibliometric analysis about lumbosacral plexus injury.

BACKGROUND: Lumbosacral plexus injury is a highly distressing clinical issue with profound implications for patients' quality of life. Since the publication of the first relevant study in 1953, there has been very limited progress in basic research and clinical treatment in this field, and the developmental trajectory and research priorities in this field have not been systematically summarized using scientific methods, leaving the future direction of this research to be explored. METHODS: Utilizing publications from the Web of Science (WoS) database, our research employed bibliometric methodology to analyze the fundamental components of publications, synthesize research trends, and forecast future directions. RESULTS: A total of 150 publications were included in our study, and the impressive advancement of research heat in this field can be attributed to the continuous increase in the number of papers, ranging from 14 papers in 2000 to 34 papers in 2023 over 5 years. Regarding the country, a central position in both quantity (H-index=125) and quality of publications (65 publications) is occupied by the United States, and close collaborations with other countries are observed. In terms of publication institutions, the highest number of publications (nine publications) is held by the Second Military Medical University. The journal with the most publications (five publications) is the Journal of Trauma-Injury Infection and Critical Care. A pivotal role has been played by basic medical research in the development of this field. Concerning hotspots, the focus of the research core can be divided into three clusters (etiology, diagnosis and treatment; molecular, cells and mechanisms; physiology, and pathology). CONCLUSION: This marks the inaugural bibliometric analysis of lumbosacral plexus injuries, offering a comprehensive overview of current publications. Our findings illuminate future research directions, international collaborations, and interdisciplinary relationships. Future research will emphasize clinical treatment and mechanism research, with a focus on sacral nerve stimulation and nerve transplantation.

Plant size traits are key contributors in the spatial variation of net primary productivity across terrestrial biomes in China.

Understanding the spatial variability of ecosystem functions is an important step forward in predicting changes in ecosystems under global transformations. Plant functional traits are important drivers of ecosystem functions such as net primary productivity (NPP). Although trait-based approaches have advanced rapidly, the extent to which specific plant functional traits are linked to the spatial diversity of NPP at a regional scale remains uncertain. Here, we used structural equation models (SEMs) to disentangle the relative effects of abiotic variables (i.e., climate, soil, nitrogen deposition, and human footprint) and biotic variables (i.e., plant functional traits and community structure) on the spatial variation of NPP across China and its eight biomes. Additionally, we investigated the indirect influence of climate and soil on the spatial variation of NPP by directly affecting plant functional traits. Abiotic and biotic variables collectively explained 62.6 % of the spatial differences of NPP within China, and 28.0 %-69.4 % across the eight distinct biomes. The most important abiotic factors, temperature and precipitation, had positive effects for NPP spatial variation. Interestingly, plant functional traits associated with the size of plant organs (i.e., plant height, leaf area, seed mass, and wood density) were the primary biotic drivers, and their positive effects were independent of biome type. Incorporating plant functional traits improved predictions of NPP by 6.7 %-50.2 %, except for the alpine tundra on the Qinghai-Tibet Plateau. Our study identifies the principal factors regulating NPP spatial variation and highlights the importance of plant size traits in predictions of NPP variation at a large scale. These results provide new insights for involving plant size traits in carbon process models.

Ratiometric electrochemiluminescence sensing and intracellular imaging of ClO- via resonance energy transfer.

Electrochemiluminescence resonance energy transfer (ECL-RET) is a versatile signal transduction strategy widely used in the fabrication of chem/biosensors. However, this technique has not yet been applied in visualized imaging analysis of intracellular species due to the insulating nature of the cell membrane. Here, we construct a ratiometric ECL-RET analytical method for hypochlorite ions (ClO-) by ECL luminophore, with a luminol derivative (L-012) as the donor and a fluorescence probe (fluorescein hydrazide) as the acceptor. L-012 can emit a strong blue ECL signal and fluorescein hydrazide has negligible absorbance and fluorescence signal in the absence of ClO-. Thus, the ECL-RET process is turned off at this time. In the presence of ClO-, however, the closed-loop hydrazide structure in fluorescein hydrazide is opened via specific recognition with ClO-, accompanied with intensified absorbance and fluorescence signal. Thanks to the spectral overlap between the ECL spectrum of L-012 and the absorption spectrum of fluorescein, the ECL-RET effect is gradually recovered with the addition of ClO-. Furthermore, the ECL-RET system has been successfully applied to image intracellular ClO-. Although the insulating nature of the cell itself can generate a shadow ECL pattern in the cellular region, extracellular ECL emission penetrates the cell membrane and excites intracellular fluorescein generated by the reactions between fluorescein hydrazide and ClO-. The cell imaging strategy via ECL-RET circumvents the blocking of the cell membrane and enables assays of intracellular species. The importance of the ECL-RET platform lies in calibrating the fluctuation from the external environment and improving the selectivity by using fluorescent probes. Therefore, this ratiometric ECL sensor has shown broad application prospects in the identification of targets in clinical diagnosis and environmental monitoring.

Integration of single-cell and RNA-seq data to explore the role of focal adhesion-related genes in osteoporosis.

Integrin-based focal adhesion is one of the major mechanosensory in osteocytes. The aim of this study was to mine the hub genes associated with focal adhesion and investigate their roles in osteoporosis based on the data of single-cell RNA sequencing and RNA-sequencing. Two hub genes (FAM129A and RNF24) with the same expression trend and AUC values greater than 0.7 in both GSE56815 and GSE56116 cohorts were uncovered. The nomogram was created to predict the risk of OP based on two hub genes. Subsequently, the competing endogenous RNA network was established based on two hub genes, 14 microRNAs and five long noncoding RNAs. Meanwhile, transcription factors-hub gene network was established based on two hub genes and 14 TFs. Finally, 73 drugs were predicted, of which there were 13 drugs targeting FAM129A and 66 drugs targeting RNF24. In both mouse and human blood samples, FAM129A expression was decreased in granulocytes and RNF24 expression was increased in monocytes. In the mouse experiment, FAM129A and anti-RNF24 were found to partially alleviate the progression of osteoporosis. In conclusion, two hub genes related to focal adhesion were identified by combined scRNA-seq and RNA-seq analyses, which might supply a new insight for the treatment and evaluation of OP.

Comprehensive review on the elaboration of payloads derived from natural products for antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have arisen as a promising class of biotherapeutics for targeted cancer treatment, combining the specificity of monoclonal antibodies with the cytotoxicity of small-molecule drugs. The choice of an appropriate payload is crucial for the success development of ADCs, as it determines the therapeutic efficacy and safety profile. This review focuses on payloads derived from natural products, including cytotoxic agents, DNA-damaging agents, and immunomodulators. These offer several advantages such as diverse chemical structures, unique mechanism of actions, and potential for improved therapeutic index. Challenges and opportunities associated with their development were highlighted. This review underscores the significance of natural product payloads in the elaboration of ADCs, which serves as a valuable resource for researchers involved in developing and optimizing next-generation ADCs for cancer treatment.