Sensitive subcellular scale and real-time detection of hydrogen peroxide by a W-doped Pt microelectrode.

A W-doped Pt modified graphene oxide (Pt-W-GO) electrochemical microelectrode was developed to detect hydrogen peroxide (H2O2) in real time at a subcellular scale. Interestingly, results showed that the concentration of H2O2 in the nucleus of HeLa cells was 2.68 times and 0.51 times that in the extracellular membrane and cytoplasm, respectively.

Association of frailty with adverse outcomes in surgically treated geriatric patients with hip fracture: A meta-analysis and trial sequential analysis.

OBJECTIVE: Some studies have associated frailty and prognostic outcomes in geriatric hip fracture patients, but whether frailty can predict postoperative outcomes remains controversial. This review aims to assess the relationship between frailty and adverse postoperative outcomes in geriatric patients with hip fracture. METHODS: Based on electronic databases, including PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang Data, we systematically searched for studies that investigated the association between frailty and adverse outcomes among patients aged 60 or over after hip fracture surgery. Stata 17.0 and Trial Sequential Analysis viewer software were used to obtain pooled estimates and verify whether the sample size was sufficient and the evidence robust. RESULTS: Twenty-one studies involving 49,196 patients were included for quantitative analysis. Compared with nonfrail patients, frail patients had a higher risk of inpatient mortality (risk ratio [RR] = 1.93, 95% confidence interval [CI]: 1.66-2.23), 30-day mortality (RR = 2.13, 95% CI: 1.23-3.70), and 1-year mortality (RR = 2.44, 95% CI: 1.47-4.04). Frailty can significantly predict postoperative complications (RR = 1.76, 95% CI: 1.38-2.23), including delirium, pneumonia, cardiac complications, urinary tract infection, and surgical site infection; the association between frailty and deep venous thrombosis/pulmonary embolism and acute kidney injury needs further analysis. Trial sequential analysis showed that the findings regarding mortality were reliable and robust. CONCLUSION: This meta-analysis provides detailed information indicating that frailty is a substantial predictor of mortality and selected postoperative complications.

s2MRI-ADNet: an interpretable deep learning framework integrating Euclidean-graph representations of Alzheimer's disease solely from structural MRI.

OBJECTIVE: To establish a multi-dimensional representation solely on structural MRI (sMRI) for early diagnosis of AD. METHODS: A total of 3377 participants' sMRI from four independent databases were retrospectively identified to construct an interpretable deep learning model that integrated multi-dimensional representations of AD solely on sMRI (called s2MRI-ADNet) by a dual-channel learning strategy of gray matter volume (GMV) from Euclidean space and the regional radiomics similarity network (R2SN) from graph space. Specifically, the GMV feature map learning channel (called GMV-Channel) was to take into consideration spatial information of both long-range spatial relations and detailed localization information, while the node feature and connectivity strength learning channel (called NFCS-Channel) was to characterize the graph-structured R2SN network by a separable learning strategy. RESULTS: The s2MRI-ADNet achieved a superior classification accuracy of 92.1% and 91.4% under intra-database and inter-database cross-validation. The GMV-Channel and NFCS-Channel captured complementary group-discriminative brain regions, revealing a complementary interpretation of the multi-dimensional representation of brain structure in Euclidean and graph spaces respectively. Besides, the generalizable and reproducible interpretation of the multi-dimensional representation in capturing complementary group-discriminative brain regions revealed a significant correlation between the four independent databases (p < 0.05). Significant associations (p < 0.05) between attention scores and brain abnormality, between classification scores and clinical measure of cognitive ability, CSF biomarker, metabolism, and genetic risk score also provided solid neurobiological interpretation. CONCLUSION: The s2MRI-ADNet solely on sMRI could leverage the complementary multi-dimensional representations of AD in Euclidean and graph spaces, and achieved superior performance in the early diagnosis of AD, facilitating its potential in both clinical translation and popularization.

A game-based multimedia application to improve the ability of clinical nurses to perform geriatric care: A randomized controlled trial.

BACKGROUND: Given the realities of global aging, maintaining Comprehensive Geriatric Assessment (CGA) abilities among clinical nurses is very important. Newer methods of continuing education are needed to engage nurses in CGA education. Using multimedia and game-based applications in CGA education (CGA APP) may be an effective method for continuing education. OBJECTIVES: To test the effectiveness of CGA APP in improving nurses' confidence in their abilities to perform geriatric care. DESIGN: A randomized, controlled trial were adopted. SETTING: An 1343-bed tertiary-care medical center in southern Taiwan. PARTICIPANTS: A total of 1250 nurses met inclusion criteria in 35 adult wards. We employed stratified sampling to recruit a total of 132 nurses proportional to the number of nurses in each ward, from January to March 2019. METHODS: Based on the Octalysis gamification framework, the CGA APP was developed. Participants were randomly assigned to either an CGA APP or a control group, which received traditional classroom learning of the same content. The main outcome was improvement in confidence in geriatric care ability were measured before and end of the training session, and six months later. RESULTS: There were no differences in baseline characteristics (except years of experience as a registered nurse), knowledge, attitudes or confidence of geriatric care between the two groups. Clinical nurses in the CGA APP group demonstrated significantly higher confidence in their geriatric care abilities than control group immediately after the intervention (75.85 ± 10.71 vs. 65.93 ± 8.49, p < 0.001) and six-months later (71.13 ± 9.69 vs. 63.57 ± 8.78, p < 0.001). After using GEE to control the confounding variable, the CGA APP group remained significantly higher confidence in their geriatric care abilities than control group. CONCLUSIONS: Use of multimedia game-based applications my better engage and teach practicing clinical than traditional learning methods. Our findings suggest that such interventions be further developed and tested for a larger variety of continuing education needs.

An eco-friendly porous hydrogel adsorbent based on dextran/phosphate/amino for efficient removal of Be(II) from aqueous solution.

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (Kd = 1.53 × 104 mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution.

Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity.

The clinical applications of immunocytokines are severely restricted by dose-limiting toxicities. To address this challenge, here we propose a next-generation immunocytokine concept involving the design of LH05, a tumor-conditional anti-PD-L1/interleukin-15 (IL-15) prodrug. LH05 innovatively masks IL-15 with steric hindrance, mitigating the "cytokine sink" effect of IL-15 and reducing systemic toxicities associated with wild-type anti-PD-L1/IL-15. Moreover, upon specific proteolytic cleavage within the tumor microenvironment, LH05 releases an active IL-15 superagonist, exerting potent antitumor effects. Mechanistically, the antitumor efficacy of LH05 depends on the increased infiltration of CD8+ T and natural killer cells by stimulating the chemokines CXCL9 and CXCL10, thereby converting cold tumors into hot tumors. Additionally, the tumor-conditional anti-PD-L1/IL-15 can synergize with an oncolytic virus or checkpoint blockade in advanced and metastatic tumor models. Our findings provide a compelling proof of concept for the development of next-generation immunocytokines, contributing significantly to current knowledge and strategies of immunotherapy.

Distinct Assembly Patterns of Soil Antibiotic Resistome Revealed by Land-Use Changes over 30 Years.

Compared with the ever-growing information about the anthropogenic discharge of nutrients, metals, and antibiotics on the disturbance of antibiotic resistance genes (ARGs), less is known about how the potential natural stressors drive the evolutionary processes of antibiotic resistance. This study examined how soil resistomes evolved and differentiated over 30 years in various land use settings with spatiotemporal homogeneity and minimal human impact. We found that the contents of soil organic carbon, nitrogen, soil microbial biomass, and bioavailable heavy metals, as well as related changes in the antibiotic resistome prevalence including diversity and abundance, declined in the order of grassland > cropland > bareland. Sixty-nine remaining ARGs and 14 mobile genetic elements (MGEs) were shared among three land uses. Multiple factors (i.e., soil properties, heavy metals, bacterial community, and MGEs) contributed to the evolutionary changes of the antibiotic resistome, wherein the resistome profile was dominantly driven by MGEs from both direct and indirect pathways, supported by a partial least-squares path model analysis. Our results suggest that pathways to mitigate ARGs in soils can coincide with land degradation processes, posing a challenge to the common goal of managing our environment sustainably.

Integrated molybdenum single atom array sensors with multichannels for nitrite detection in foods.

Nitrite (NO2-) is present in a variety of foods, but the excessive intake of NO2- can indirectly lead to carcinogenic, teratogenic, mutagenicity and other risks to the human body. Therefore, the detection of NO2- is crucial for maintaining human health. In this study, an integrated array sensor for NO2- detection is developed based on molybdenum single atom material (IMSMo-SAC) using high-resolution electrohydrodynamic (EHD) printing technology. The sensor comprises three components: a printed electrode array, multichannels designed on polydimethylsiloxane (PDMS) and an electronic signal process device with bluetooth. By utilizing Mo-SAC to facilitate electron transfer during the redox reaction, rapid and efficient detection of NO2- can be achieved. The sensor has a wide linear range of 0.1 µM-107.8 mM, a low detection limit of 33 nM and a high sensitivity of 0.637 mA-1mM-1 cm-2. Furthermore, employing this portable array sensor allows simultaneously measurements of NO2- concentrations in six different foods samples with acceptable recovery rates. This array sensor holds great potential for detecting of small molecules in various fields.

Clinimetric properties of the "FIND-NEEDS" to screen geriatric conditions.

INTRODUCTION: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. METHODS: First-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). RESULTS: The mean age of the 114 outpatients was 78.3±7.6 years, and 79(69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r=0.494; p<0.001), and the binary score showed excellent correlation (r=0.944; p<0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). DISCUSSION/CONCLUSION: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.

Supramolecular channels via crown ether functionalized polyaniline for proton-self-doped cathode in aqueous zinc-ion battery.

Polyaniline (PANI) has been widely used as a cathode in aqueous zinc-ion batteries (AZIBs) because of its attractive conductivity and energy storage capability. However, the extensive application of PANI is limited by spontaneous deprotonation and slow diffusion kinetics. Herein, an 18-crown-6-functionalised PANI pseudorotaxane (18C6@PANI) cathode is successfully developed through a facile template-directed polymerisation reaction. The 18C6@PANI cathode exhibits a high specific capacity of 256 mAh g-1 at 0.2 A/g, excellent rate performance of 134 mAh g-1 at 6 A/g and outstanding cycle stability at a high current density of 3 A/g over 10,000 cycles. Experimental and theoretical analyses demonstrate the formation of the -N-Zn-O- structure. The abundant supramolecular channels in pseudorotaxane, induced by crown ether functional groups, are beneficial for achieving superior cyclability and rate capability. These encouraging results highlight the potential for designing more efficient PANI-based cathodes for high-performance AZIBs.

The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.

Integrated metabolomic and transcriptomic analysis of triterpenoid accumulation in the roots of Codonopsis pilosula var. modesta (Nannf.) L.T.Shen at different altitudes.

INTRODUCTION: Codonopsis Radix is a beneficial traditional Chinese medicine, and triterpenoid are the major bioactive constituents. Codonopsis pilosula var. modesta (Nannf.) L.T.Shen (CPM) is a precious variety of Codonopsis Radix, which is distributed at high mountain areas. The environment plays an important role in the synthesis and metabolism of active ingredients in medicinal plants, but there is no report elaborating on the effect of altitude on terpenoid metabolites accumulation in CPM. OBJECTIVES: This study aims to analyse the effects of altitude on triterpenoid biosynthetic pathways and secondary metabolite accumulation in CPM. MATERIAL AND METHODS: The untargeted metabolomics based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 10 triterpenoids based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method were analysed at the low-altitude (1480 m) and high-altitude (2300 m) CPM fresh roots. The transcriptome based on high-throughput sequencing technology were combined to analyse the different altitude CPM triterpenoid biosynthetic pathways. RESULTS: A total of 17,351 differentially expressed genes (DEGs) and 55 differentially accumulated metabolites (DAMs) were detected from the different altitude CPM, and there are significant differences in the content of the 10 triterpenoids. The results of transcriptome study showed that CPM could significantly up-regulate the gene expression levels of seven key enzymes in the triterpenoid biosynthetic pathway. CONCLUSIONS: The CPM at high altitude is more likely to accumulate triterpenes than those at low altitude, which was related to the up-regulation of the gene expression levels of seven key enzymes. These results expand our understanding of how altitude affects plant metabolite biosynthesis.

Dynamic changes of immunocyte subpopulations in thermogenic activation of adipose tissues.

Objectives: The effects of cold exposure on whole-body metabolism in humans have gained increasing attention. Brown or beige adipose tissues are crucial in cold-induced thermogenesis to dissipate energy and thus have the potential to combat metabolic disorders. Despite the immune regulation of thermogenic adipose tissues, the overall changes in vital immune cells during distinct cold periods remain elusive. This study aimed to discuss the overall changes in immune cells under different cold exposure periods and to screen several potential immune cell subpopulations on thermogenic regulation. Methods: Cibersort and mMCP-counter algorithms were employed to analyze immune infiltration in two (brown and beige) thermogenic adipose tissues under distinct cold periods. Changes in some crucial immune cell populations were validated by reanalyzing the single-cell sequencing dataset (GSE207706). Flow cytometry, immunofluorescence, and quantitative real-time PCR assays were performed to detect the proportion or expression changes in mouse immune cells of thermogenic adipose tissues under cold challenge. Results: The proportion of monocytes, naïve, and memory T cells increased, while the proportion of NK cells decreased under cold exposure in brown adipose tissues. Conclusion: Our study revealed dynamic changes in immune cell profiles in thermogenic adipose tissues and identified several novel immune cell subpopulations, which may contribute to thermogenic activation of adipose tissues under cold exposure.

Effects of Smoking on Major Adverse Cardiovascular Events in Patients With Coronary Artery Spasm: A Systematic Review and Meta-Analysis.

BACKGROUND: Smoking is an established independent risk factor for coronary artery spasm (CAS), but its effects on major adverse cardiovascular events (MACE) in patients with CAS have not been systematically assessed. METHODS: This systematic review and meta-analysis of studies published from January 2000 to July 2023 was conducted to examine the relationship between smoking and MACE in patients with CAS. Data on MACE were obtained from both smoking and non-smoking CAS patient groups. The effects of smoking on MACE in patients with CAS were assessed through meta-analysis, utilising Stata 17.0 software for all statistical analyses. RESULTS: Nine studies, encompassing 9,376 patients, from Japan (5 studies), Korea (4 studies) and Spain (1 study) were included in the final analysis. Meta-analysis revealed that smoking significantly impacted MACE in patients with CAS (RR 1.965; 95% CI 1.348-2.865), a finding further validated by sensitivity analyses. Subgroup analyses identified a stronger correlation between smoking and increased MACE endpoints in Japanese patients and in those with >3 years of follow-up. CONCLUSIONS: This meta-analysis strongly indicates that smoking escalates the risk of MACE in patients with CAS, with a more pronounced association observed in Japanese patients and those with extended follow-up periods.

Importance of AIM2 as a serum marker for reflecting severity and predicting a poor outcome of human severe traumatic brain injury: A prospective longitudinal cohort study.

BACKGROUND: Absent in melanoma 2 (AIM2) participates in neuroinflammation. Here, the prognostic significance of serum AIM2 was explored in severe traumatic brain injury (sTBI). METHODS: A total of 135 sTBI patients and 80 healthy controls were recruited in this prospective cohort study. Serum C-reactive protein (CRP) and AIM2 levels were measured. Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) classification were recorded as the severity indicators. Prognostic parameters were posttraumatic six-month extended Glasgow outcome scale (GOSE) scores and poor outcome (GOSE scores of 1-4). RESULTS: As opposed to controls, there were significantly elevated serum AIM2 levels after sTBI. Serum AIM2 levels were independently correlated with serum CRP levels, GCS scores, Rotterdam CT scores, GOSE scores and poor outcome. Also, serum AIM2 levels were efficiently predictive of poor outcome under the receiver operating characteristic (ROC) curve. Under the restricted cubic spline, serum AIM2 levels were linearly correlated with risk of poor outcome. Using subgroup analysis, serum AIM2 levels did not significantly interact with other indices, such as age, gender, alcohol drinking, cigarette smoking, etc. Also, combination model, in which serum AIM2, GCS scores and Rotterdam CT scores were merged, was outlined using nomogram and performed well under calibration curve, ROC curve and decision curve. CONCLUSIONS: Raised serum AIM2 levels after sTBI, in intimate correlation with systemic inflammation and trauma severity, are independently discriminative of posttraumatic six-month neurological outcome, substantializing serum AIM2 as an inflammatory prognostic biomarker of sTBI.

Modeling refined differences of cortical folding patterns via spatial, morphological, and temporal fusion representations.

The gyrus, a pivotal cortical folding pattern, is essential for integrating brain structure-function. This study focuses on 2-Hinge and 3-Hinge folds, characterized by the gyral convergence from various directions. Existing voxel-level studies may not adequately capture the precise spatial relationships within cortical folding patterns, especially when relying solely on local cortical characteristics due to their variable shapes and homogeneous frequency-specific features. To overcome these challenges, we introduced a novel model that combines spatial distribution, morphological structure, and functional magnetic resonance imaging data. We utilized spatio-morphological residual representations to enhance and extract subtle variations in cortical spatial distribution and morphological structure during blood oxygenation, integrating these with functional magnetic resonance imaging embeddings using self-attention for spatio-morphological-temporal representations. Testing these representations for identifying cortical folding patterns, including sulci, gyri, 2-Hinge, and 2-Hinge folds, and evaluating the impact of phenotypic data (e.g. stimulus) on recognition, our experimental results demonstrate the model's superior performance, revealing significant differences in cortical folding patterns under various stimulus. These differences are also evident in the characteristics of sulci and gyri folds between genders, with 3-Hinge showing more variations. Our findings indicate that our representations of cortical folding patterns could serve as biomarkers for understanding brain structure-function correlations.

Detection of a Human Adenovirus Outbreak, Including Some Critical Infections, Using Multipathogen Testing at a Large University, September 2022-January 2023.

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

Development and testing of a four-item version of the physical resilience instrument for older adults (PRIFOR-4).

The 16-item Physical Resilience Instrument for Older Adults (PRIFOR) has good clinimetric properties; however, a shortened PRIFOR would greatly enhance physical resilience measurements in clinical settings. The current analysis aimed to reduce the number of PRIFOR while maintaining its clinimetric properties, emphasizing on its factor structure and convergent validity. A longitudinal study was conducted among 863 patients aged 65 years or older. Four PRIFOR items with high factor loadings were selected to generate the short version of PRIFOR (PRIFOR-4). The PRIFOR-4 was found to have a unidimensional structure (comparative fit index = 0.999; Tucker-Lewis index = 0.998 in the confirmatory factor analysis results) with good convergent validity with various external measures (absolute r = 0.109-0.597; p-values<0.01). Because the PRIFOR-4 contains only four items, the completion time for the respondents reduced three fourths from the original PRIFOR, which may have a marked reduction in the response burden. The PRIFOR-4 is thus an easy-to-use measurement that saves time for healthcare professionals in clinical practice.

Microbial-induced carbonate precipitation effectively prevents Pb2+ migration through the soil profile: Lab experiment and model simulation.

Due to the inappropriate disposal of waste materials containing lead (Pb) and irrigation with sewage containing Pb, the migration of Pb2+ within the soil profile has been extensively investigated. The conventional Pb2+ block method is challenging to implement due to its complex operational procedures and high construction costs. To address this issue, this study introduces the microbial-induced carbonate precipitation (MICP) technique as a novel approach to impede the migration of Pb2+ in the soil profile. Soil acclimatization with urea resulted in an increased proportion of urease-producing microorganisms, including Bacillus, Paenibacillus, and Planococcaceae, along with heightened expression of urea-hydrolyzing genes (UreA, UreB, UreC, and UreG). This indicates that urea-acclimatized soil (Soil-MICP) possesses the potential to induce carbonate precipitation. Batch Pb2+ fixation experiments confirmed that the fixation efficiency of Soil-MICP on Pb2+ exceeded that of soil without MICP, attributed to the MICP process within the Soil-MICP group. Dynamic migration experiments revealed that the MICP reaction transformed exchangeable lead into carbonate-bound Pb, effectively impeding Pb2+ migration in the soil profile. Additionally, the migration rate of Pb2+ in Soil-MICP was influenced by varying urea amounts, pH levels, and pore flow rates, leading to a slowdown in migration. The Two-site sorption model aptly described the Pb2+ migration process in the Soil-MICP column. This study aims to elucidate the MICP biomineralization process, uncover the in-situ blocking mechanism of MICP on lead in soil, investigate the impact of Pb on key genes involved in urease metabolism, enhance the comprehension of the chemical morphology of lead mineralization products, and provide a theoretical foundation for MICP technology in preventing the migration of Pb2+ in soil profiles.

A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy.

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.