UIO66 low background signal and fluorescence synergism strategy for highly sensitive detection of Salmonella typhimurium.

Successful construction of a detection method for Salmonella typhimurium (S. typhimurium) based on the synergy of hybridization chain reaction (HCR) and fluorescence was realized in this paper. First, the aptamer modified with the quenching group Black Hole Quencher-1 acid (BHQ1) was immobilized on the magnetic beads in combination with the complementary chain of the aptamer modified with 6-carboxyfluorescein (6-FAM). Second, S. typhimurium and cDNA-6-FAM immobilized on magnetic beads competitively bound to the aptamer. Finally, the cDNA-6-FAM was released after magnetic separation acted as a promoter to trigger HCR amplification when the target presented. The fluorescence signal could be significantly improved by the combination of green SYBR Green I (SGI) and HCR long double-stranded DNA and the fluorescent synergy of 6-FAM and SGI. Because of the separation of target and its aptamer, the trigger strand was abstracted by magnetic separation. There was no HCR to generate long double-stranded DNA, and the fluorescence of excess hairpin/SGI could be adsorbed through UIO66 so that only a very low background signal was detected. This fluorescent sensor was capable of monitoring S. typhimurium in the range of 10-3.2 × 107 CFU mL-1 with a limit of detection as low as 1.5 CFU mL-1. Because of the excellent properties of the aptasensor and the validity of SGI fluorescence synergy, this HCR enzyme-free amplification strategy could be generalized to other areas.

Defect-rich sonosensitizers based on CeO2 with Schottky heterojunctions for boosting sonodynamic/chemodynamic synergistic therapy.

Sonodynamic therapy (SDT) has been recognized as a promising treatment for cancer due to its advantages of superior specificity, non-invasiveness, and deep tissue penetration. However, the antitumor effect of SDT remains restricted by the limited generation of reactive oxygen species (ROS) due to the lack of highly efficient sonosensitizers. In this work, we developed the novel sonosensitizer Pt/CeO2-xSx by constructing oxygen defects through S doping and Pt loading in situ. Large amounts of oxygen defects have been obtained by S doping, endowing Pt/CeO2-xSx with the ability to suppress electron-hole recombination, further promoting ROS production. Moreover, the introduction of Pt nanoparticles can not only produce oxygen in situ for relieving hypoxia but also form a Schottky heterojunction with CeO2-xSx for further inhibiting electron-hole recombination. In addition, Pt/CeO2-xSx could effectively deplete overexpressed glutathione (GSH) via redox reactions, amplifying oxidative stress in the tumor microenvironment (TME). Combined with the excellent POD-mimetic activity, Pt/CeO2-xSx can achieve highly efficient synergistic therapy of SDT and chemodynamic therapy (CDT). All these findings demonstrated that Pt/CeO2-xSx has great potential for cancer therapy, and this work provides a promising direction for designing and constructing efficient sonosensitizers.

Structural basis of translation inhibition by a valine tRNA-derived fragment.

Translational regulation by non-coding RNAs is a mechanism commonly used by cells to fine-tune gene expression. A fragment derived from an archaeal valine tRNA (Val-tRF) has been previously identified to bind the small subunit of the ribosome and inhibit translation in Haloferax volcanii Here, we present three cryo-electron microscopy structures of Val-tRF bound to the small subunit of Sulfolobus acidocaldarius ribosomes at resolutions between 4.02 and 4.53 Å. Within these complexes, Val-tRF was observed to bind to conserved RNA-interacting sites, including the ribosomal decoding center. The binding of Val-tRF destabilizes helices h24, h44, and h45 and the anti-Shine-Dalgarno sequence of 16S rRNA. The binding position of this molecule partially overlaps with the translation initiation factor aIF1A and occludes the mRNA P-site codon. Moreover, we found that the binding of Val-tRF is associated with steric hindrance of the H69 base of 23S rRNA in the large ribosome subunit, thereby preventing 70S assembly. Our data exemplify how tRNA-derived fragments bind to ribosomes and provide new insights into the mechanisms underlying translation inhibition by Val-tRFs.

Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Conjugation and Topology Engineering of 2D π-d Conjugated Metal-Organic Frameworks for Robust Potassium Organic Batteries.

The evolution of two-dimensional conjugated metal-organic frameworks (2D c-MOFs) provides a significant prospect for researching the next generation of green and advanced energy storage systems (ESSs). Especially, conjugation and topology engineering serve as an irreplaceable character in adjusting the electrochemical properties of ESSs. Herein, we proposed a novel strategy using conjugation and topology engineering to demonstrate the application of 2D c-MOFs in robust potassium-ion batteries (PIBs) for the first time. By comparing 2D c-MOFs with the rhombus/kagome structure as well as three/four-arm core, the rhombus structure (sql-Cu-TBA-MOF) cathode for PIBs can display the impressive electrochemical performance, including a high specific discharge capacity of 178.4 mAh g-1 (at 0.2 A g-1) and a well long-term cycle stability of more than 9,000 (at 10.0 A g-1). Moreover, full PIBs (FPIBs) are constructed by pairing sql-Cu-TBA-MOF cathode with dipotassium terephthalate (KTP) anode, which delivers a high reversible discharge specific capacity of 146.6 mAh g-1 (at 0.1 A g-1) and great practical application prospect. These findings provide reasonable implications for the design of 2D c-MOFs from the perspective of conjugation and topology engineering for advanced energy storage systems.

Secreted salt and hydrodynamic factors combine to affect dynamic fluctuations of microplastics on mangrove leaves.

Mangrove leaves have been acknowledged as crucial sink for coastal microplastics (MPs). Whereas, the temporal dynamics of MPs intercepted by mangrove leaves have remained poorly understood. Here, we detected MPs intercepted by submerged and non-submerged mangrove leaves over time and the potential driving factors. Abundance and characteristics of MPs interception by mangrove leaves exhibited dynamic fluctuations, with the coefficient of variation (CV) of submerged mangrove leaves (CV = 0.604; 1.76 n/g to 15.45 n/g) being approximately twofold higher than non-submerged mangrove leaves (CV = 0.377; 0.74 n/g to 3.28 n/g). Partial least squares path model (PLS-PM) analysis further illustrated that MPs abundance on submerged mangrove leaves were negative correlated to hydrodynamic factors (i.e., current velocity and tidal range). Intriguingly, secreted salt as a significantly driver of MPs intercepted by mangrove leaves. Results of this work highlights that MPs intercepted by mangrove leaves is characterized by dynamic fluctuations and reveals the importance of hydrodynamic factors and secreted salt. Overall, this work identifies the pivotal buffering role played by mangrove leaves in intercepting MPs, which provides basic knowledge for better understanding of microplastic pollution status and control from mangrove plants.

Single-Site Nanozymes with a Highly Conjugated Coordination Structure for Antitumor Immunotherapy via Cuproptosis and Cascade-Enhanced T Lymphocyte Activity.

The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor immune cells impede the infiltration and killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) and lysyl oxidase inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. The conjugated organic ligand and well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 and H2O2 to ·O2- and ·OH. This surge of reactive oxygen species (ROS) leads to impaired mitochondrial function and insufficient ATP supply, impacting the function of copper-transporting ATPase-1 and causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms and glutathione peroxidase 4 depletion also induce lipid peroxidation and trigger ferroptosis. Simultaneously, the ROS-triggered release of LOX-IN-3 reshapes the ECM by inhibiting lysyl oxidase activity and further enhances the infiltration of cytotoxic T lymphocytes (CD8+ T cells). CHO-triggered cholesterol depletion not only increases ·OH generation but also downregulates the expression of ICs such as PD-1 and TIM-3, restoring the antitumor activity of tumor-infiltrating CD8+ T cells. Therefore, Cu-DBCO/CL exhibits efficient properties in activating a potent antitumor immune response by cascade-enhanced CD8+ T cell viability. More importantly, ECM remodeling and cholesterol depletion could suppress the metastasis and proliferation of the tumor cells. In short, this immune nanoremodeler can greatly enhance the infiltration and antitumor activity of T cells by enhancing tumor immunogenicity, remodeling ECM, and downregulating ICs, thus achieving effective inhibition of tumor growth and metastasis.

Programmed Targeting Pyruvate Metabolism Therapy Amplified Single-Atom Nanozyme-Activated Pyroptosis for Immunotherapy.

Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single-atom nanozyme pyroptosis initiator: UK5099 and pyruvate oxidase (POx)-co-loaded Cu-NS single-atom nanozyme (Cu-NS@UK@POx), that not only trigger pyroptosis through cascade biocatalysis to boost the immunogenicity of tumor cells, but also remodel the immunosuppressive TME by targeting pyruvate metabolism. By replacing N with weakly electronegative S, the original spatial symmetry of the Cu-N4 electron distribution is changed and the enzyme-catalyzed process is effectively regulated. Compared to spatially symmetric Cu-N4 single-atom nanozymes (Cu-N4 SA), the S-doped spatially asymmetric single-atom nanozymes (Cu-NS SA) exhibit stronger oxidase activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) oxidase (NOx), L-cysteine oxidase (LCO), and glutathione oxidase (GSHOx), which can cause enough reactive oxygen species (ROS) storms to trigger pyroptosis. Moreover, the synergistic effect of Cu-NS SA, UK5099, and POx can target pyruvate metabolism, which not only improves the immune TME but also increases the degree of pyroptosis. This study provides a two-pronged treatment strategy that can significantly activate antitumor immunotherapy effects via ROS storms, NADH/glutathione/L-cysteine consumption, pyruvate oxidation, and lactic acid (LA)/ATP depletion, triggering pyroptosis and regulating metabolism. This work provides a broad vision for expanding antitumor immunotherapy.

Population Pharmacokinetics and Individualized Medication of Azithromycin for Injection in Children Under 6 Years Old.

Pharmacokinetic data for injectable azithromycin in children remain limited. This study aims to develop and validate a population pharmacokinetic model of azithromycin for injection in children under 6 years old and optimize its dosage regimen in this population. We prospectively enrolled patients under 6 years old who received azithromycin for injection at Beijing Friendship Hospital, Capital Medical University. Demographic information, clinical characteristics, and venous blood samples were collected in accordance with the research protocol. Azithromycin concentrations were determined using a validated UPLC-MS/MS method. The population pharmacokinetic model was structured using Phoenix NLME. The adequacy and robustness of the model was evaluated using VPC and bootstrap. We optimized azithromycin's dosing regimen for injection through Monte Carlo simulations. We included 254 plasma concentration data from 148 patients to establish the model. The clearance and volume were 1.27 L/h/kg and 45.6 L/kg, respectively. The covariates included were weight and age. VPC plots and nonparametric bootstrap showed that the final PPK model was reliable and robust. Based on Monte Carlo simulation, we derived a simple and practical dosing scheme. The results provided reference for individualized dosing in this population. The individualized dosing scheme based on Monte Carlo simulation can optimize clinical decision-making and guide personalized therapy.

Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.

Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage. Hence, this study aimed to elucidate the association between mitophagy and skeletal fluorosis and the precise mechanisms through which calcium alleviates these injuries. A 100 mg/L sodium fluoride (NaF) exposure model in Parkin knockout (Parkin-/-) mice and a 100 mg/L NaF exposure mouse model with 1% calcium carbonate (CaCO3) intervention were established in the current study. Fluoride exposure caused the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy and mitochondrial apoptosis in the bones, which were restored after blocking Parkin. Additionally, the intervention model showed fluoride-exposed mice exhibited abnormal bone trabecula and mechanical properties. Still, these bone injuries could be effectively attenuated by adding 1% calcium to their diet, which reversed fluoride-activated mitophagy and apoptosis. To summarize, fluoride can activate bone mitophagy through the PINK1/Parkin pathway and mitochondrial apoptosis. Parkin-/- and 1% calcium provide protection against fluoride-induced bone damage. Notably, this study provides theoretical bases for the prevention and therapy of animal and human health and safety caused by environmental fluoride contamination.

Spatiotemporal distribution and potential risks of antibiotics in coastal water of Beibu Gulf, South China Sea: Livestock and poultry emissions play essential effect.

Antibiotics have been the subject of much attention in recent years due to their widespread use and the potential ecological risks and resistance risks. In this study, we conducted an extensive survey of 19 antibiotics in a wide range of waters of the Beibu Gulf during summer and winter (154 samples). The total concentrations of the 19 antibiotics (Σ19ABs, ng/L) were significantly higher in winter (n.d.-364) than in summer (n.d.-70.1) and were mainly concentrated in areas of seagoing rivers (1.50-364). The primary route for antibiotics entering Beibu Gulf was through riverine input. Precisely, florfenicol (FF) (n.d.-278 ng/L) discharged from livestock and poultry farms upstream of Nanliu River, predominantly in swine farming, constitutes the main pollutant in Beibu Gulf throughout the year. The Nanliu River (988 kg/a) accounts for 85% of the gulf's total annual antibiotic emission flux. Source analysis identified livestock and poultry farming, particularly swine farming, as the primary pollution source, contributing 58% in summer. Risk assessment reveals that algae (0.51 ± 0.56) exhibited relatively high sensitivity to antibiotics, presenting a medium-high risk at specific sites in Nanliu River during winter. Additionally, FF discharged from swine farming demonstrates a certain level of antibiotic resistance risk. Therefore, reinforcing control measures for antibiotic discharges from livestock and poultry farming, especially upstream of Nanliu River, can effectively mitigate antibiotic-related risks in the water bodies of Beibu Gulf.

Distribution and adsorption-desorption of organophosphate esters from land to sea in the sediments of the Beibu Gulf, South China Sea: Impact of seagoing river input.

Organophosphate esters (OPEs) have been a class of emerging environmental contaminants. However, studies on their environmental behavior, specifically their adsorption-desorption behavior between sediment and seawater in estuarine and coastal areas, remain limited. To address this gap, our study focused on investigating the levels and behavior of 11 OPEs in sediment samples collected from the Beibu Gulf, South China Sea, encompassing estuaries and coastal regions. The total concentrations of 11 OPEs (Σ11OPEs) in the sediments exhibit a significant decrease in summer, both in seagoing rivers (4.67 ± 2.74 ng/g dw) and the coastal zone (5.11 ± 3.71 ng/g dw), compared to winter levels in seagoing rivers (8.26 ± 4.70 ng/g dw) and the coastal zone (7.71 ± 3.83 ng/g dw). Chlorinated OPEs dominated the sediments, constituting 63 %-76 % of the total. Particularly, port and mariculture areas showed the highest levels of OPEs. Through load estimation analysis, it was revealed that the sedimentary OPEs in Qinzhou Bay (221 ± 128 kg) had the highest load, with input from the Qin River identified as a significant source. Chlorinated OPEs showed a trend of desorption from sediments to the water column with increasing salinity, emphasizing the crucial role of land-based OPEs input through suspended particulate matter in rivers as a pathway to the ocean. The impact of strong flow in estuarine environments was highlighted, as it can scour sediments, generate suspended sediments, and release OPEs into the water bodies. Additionally, the results of the ecological risk assessment indicated that most of the OPEs posed low-risk levels. However, attention is warranted for the contamination levels of some chlorinated OPEs, emphasizing the need for ongoing monitoring and assessment.

Influence of hydrogen bonds on the reaction of guanine and hydroxyl radical: DFT calculations in C(H+)GC motif.

A comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bonds (H-bonds) on the obscure reaction of a hydroxyl radical (HO˙) and guanine (G) by selecting the building block of parallel triplex DNA, C(H+)GC, as the model. By mapping the energy profiles for addition and hydrogen abstraction reactions, the favorable pathway is predicted. The results reveal that in the C(H+)GC context, barrierless hydrogen abstraction from N2 of G leading to a neutral radical G(N2-H)˙ appears to become significant, but electrophilic attack by HO˙ on C8 of G resulting in 8-oxoG is the most thermodynamically favorable course. This shows a strong structural dependence due to the context constrained by the H-bond, which is dramatically different from the situation in unencumbered G. More interestingly, it proves that the stability order of resulting adduct radicals is not altered by H-bonding, but the activity for possible sites of the hydroxylation reaction changes. The significant influence of the H-bond on elementary reactions involved in the reaction is emphasized in the C(H+)GC context but is not restricted to the H-abstraction reaction. It is greatly anticipated that the present study could provide thoughtful insights into the vague hydroxyl radical-induced oxidation chemistry.

NLISA versus enzyme-linked immunosorbent assay: Nanozyme-linked immunosorbent array based on platinum sub-nanocluster nanozyme for α-fetoprotein detection.

Rapid and accurate identification of tumor metabolic markers is important for early tumor diagnosis and individualized treatment. Here, a stable monodisperse sub-nanometer platinum (Pt) material was developed as a highly efficient nanozyme with a specific activity of peroxidase as high as 20.86 U mg-1 through the growth of in situ domain-limited Pt quantum dots via the polymer polyvinylpyrrolidone. Further, the synthesis of large quantities of Pt-loaded SiO2 (Pt-SiO2 ) was determined by silylation reaction and used for naked eye colorimetric testing of human alpha-fetoprotein (AFP). In particular, the immunization incubation process occurred in preprepared microplates. A nanozyme-based immunomodel was constructed in the presence of the target AFP, and a chromogenic reaction occurred with exogenous hydrogen peroxide and the chromogenic substrate tetramethylbenzidine. On optimization of experimental conditions, the dynamic working response range for AFP was found to be 0.05-20 ng mL-1 , with a limit of detection of 38.7 pg mL-1 . This work provides a new strategy to design efficient nanozyme-based enzyme-linked immunochromatographic platforms to meet the practical use of replacing natural enzymes.

Model Generalizability Investigation for GFCE-MRI Synthesis in NPC Radiotherapy Using Multi-Institutional Patient-Based Data Normalization.

Recently, deep learning has been demonstrated to be feasible in eliminating the use of gadoliniumbased contrast agents (GBCAs) through synthesizing gadolinium-free contrast-enhanced MRI (GFCE-MRI) from contrast-free MRI sequences, providing the community with an alternative to get rid of GBCAs-associated safety issues in patients. Nevertheless, generalizability assessment of the GFCE-MRI model has been largely challenged by the high inter-institutional heterogeneity of MRI data, on top of the scarcity of multi-institutional data itself. Although various data normalization methods have been adopted to address the heterogeneity issue, it has been limited to single-institutional investigation and there is no standard normalization approach presently. In this study, we aimed at investigating generalizability of GFCE-MRI model using data from seven institutions by manipulating heterogeneity of MRI data under five popular normalization approaches. Three state-of-the-art neural networks were applied to map from T1-weighted and T2-weighted MRI to contrast-enhanced MRI (CE-MRI) for GFCE-MRI synthesis in patients with nasopharyngeal carcinoma. MRI data from three institutions were used separately to generate three uni-institution models and jointly for a tri-institution model. The five normalization methods were applied to normalize the data of each model. MRI data from the remaining four institutions served as external cohorts for model generalizability assessment. Quality of GFCE-MRI was quantitatively evaluated against ground-truth CE-MRI using mean absolute error (MAE) and peak signal-to-noise ratio(PSNR). Results showed that performance of all uni-institution models remarkably dropped on the external cohorts. By contrast, model trained using multi-institutional data with Z-Score normalization yielded the best model generalizability improvement.

Coarse-Super-Resolution-Fine Network (CoSF-Net): A Unified End-to-End Neural Network for 4D-MRI With Simultaneous Motion Estimation and Super-Resolution.

Four-dimensional magnetic resonance imaging (4D-MRI) is an emerging technique for tumor motion management in image-guided radiation therapy (IGRT). However, current 4D-MRI suffers from low spatial resolution and strong motion artifacts owing to the long acquisition time and patients' respiratory variations. If not managed properly, these limitations can adversely affect treatment planning and delivery in IGRT. In this study, we developed a novel deep learning framework called the coarse-super-resolution-fine network (CoSF-Net) to achieve simultaneous motion estimation and super-resolution within a unified model. We designed CoSF-Net by fully excavating the inherent properties of 4D-MRI, with consideration of limited and imperfectly matched training datasets. We conducted extensive experiments on multiple real patient datasets to assess the feasibility and robustness of the developed network. Compared with existing networks and three state-of-the-art conventional algorithms, CoSF-Net not only accurately estimated the deformable vector fields between the respiratory phases of 4D-MRI but also simultaneously improved the spatial resolution of 4D-MRI, enhancing anatomical features and producing 4D-MR images with high spatiotemporal resolution.

Multi-Enzyme Co-Expressed Nanomedicine for Anti-Metastasis Tumor Therapy by Up-Regulating Cellular Oxidative Stress and Depleting Cholesterol.

Tumor cells movement and migration are inseparable from the integrity of lipid rafts and the formation of lamellipodia, and lipid rafts are also a prerequisite for the formation of lamellipodia. Therefore, destroying the lipid rafts is an effective strategy to inhibit tumor metastasis. Herein, a multi-enzyme co-expressed nanomedicine: cholesterol oxidase (CHO) loaded Co─PN3 single-atom nanozyme (Co─PN3 SA/CHO) that can up-regulate cellular oxidative stress, disrupt the integrity of lipid rafts, and inhibit lamellipodia formation to induce anti-metastasis tumor therapy, is developed. In this process, Co─PN3 SA can catalyze oxygen (O2 ) and hydrogen peroxide (H2 O2 ) to generate reactive oxygen species (ROS) via oxidase-like and Fenton-like properties. The doping of P atoms optimizes the adsorption process of the intermediate at the active site and enhances the ROS generation properties of nanomedicine. Meantime, O2 produced by catalase-like catalysis can combine with excess cholesterol to generate more H2 O2 under CHO catalysis, achieving enhanced oxidative damage to tumor cells. Most importantly, cholesterol depletion in tumor cells also disrupts the integrity of lipid rafts and inhibits the formation of lamellipodia, greatly inhibiting the proliferation and metastasis of tumor cells. This strategy by up-regulating cellular oxidative stress and depleting cellular cholesterol constructs a new idea for anti-metastasis-oriented cancer therapy strategies.

Insight into the role of niche concept in deciphering the ecological drivers of MPs-associated bacterial communities in mangrove forest.

Myriad inherent and variable environmental features are controlling the assembly and succession of bacterial communities colonizing on mangrove microplastics (MPs). However, the mechanisms governing mangrove MPs-associated bacterial responses to environmental changes still remain unknown. Here, we assessed the dissimilarities of MPs-associated bacterial composition, diversity and functionality as well as quantified the niche variations of each taxon on plastispheres along river-mangrove-ocean and mangrove landward-to-seaward gradients in the Beibu Gulf, China, respectively. The bacterial richness and diversity as well as the niche breadth on mangrove sedimentary MPs dramatically decreased from landward to seaward regions. Characterizing the niche variations linked the difference of ecological drivers of MPs-associated bacterial populations and functions between river-mangrove-ocean (microplastic properties) and mangrove landward-to-seaward plastispheres (sediment physicochemical properties) to the trade-offs between selective stress exerted by inherent plastic substrates and microbial competitive stress imposed by environmental conditions. Notably, Rhodococcus erythropolis was predicted to be the generalist species and closely associated to biogeochemical cycles of mangrove plastispheres. Our work provides a reliable pathway for tackling the hidden mechanisms of environmental factors driving MPs-associated microbe from perspectives of niches and highlights the spatial dynamic variations of mangrove MPs-associated bacteria.

A novel mathematical model and application software for estimating the age of necrophagous fly larvae.

The change in larval body length of necrophagous flies during their development is a key indicator for estimating larval age. However, existing forensic entomological models have limitations in this regard. In this study, a logistic algorithm was used to establish a general model for estimating the minimum postmortem interval (PMImin) using larval body length. The new model was used to simulate the relationship between larval body length and developmental time of eight species of necrophagous flies. The model parameters of body length variation with developmental time of the different species were calculated. Computer software was developed based on the established logistic model. The advantage of the new model is that each parameter has a biological meaning and can be used to estimate the age of larvae at any temperature and any larval body length. Cross-validation of the model showed that the overall mean accuracy of the fitted growth curves for the eight necrophagous fly larvae was 82.7%, the mean accuracy of age extrapolations for seven necrophagous fly species ranged from 76.8% to 92.9%, while the accuracy of age extrapolations for only one species was lower (i.e., 63.3%). This study provides a new method to estimate the PMImin based on larval body length, and the developed computer software will facilitate its application in forensic entomology.

Protective effect of small extracellular vesicles (EVs) derived from ACE2-modified human umbilical cord mesenchymal stem cells against renal ischemia-reperfusion injury.

AIM: Acute kidney injury is a severe disease that is closely associated with substantial morbidity and mortality. The most common cause of AKI is renal ischemia-reperfusion injury. Mesenchymal stem cells (MSCs) have previously been shown to have renoprotective effects. However, extracellular vesicles secreted by MSCs are thought to be the key for the therapeutic effects of MSCs. This study investigated whether small EVs derived from ACE2-modified human umbilical cord MSCs could alleviate RIRI and explored their underlying molecular mechanisms METHODS: A lentivirus carrying an ACE2 overexpression vector was constructed and used to infect MSCs. The small EVs were isolated from MSC-conditioned medium by ultracentrifugation. HK-2 cells were cocultured with MSC-ACE2-EVs and subjected to hypoxia/reoxygenation injury. MSCs-ACE2-EVs were injected into RIRI mice. Biochemical and morphological characteristics were assessed, and the levels of inflammatory-related factors, oxidative stress products, and apoptosis in HK-2 cells and kidney tissues were assessed RESULTS: In vitro, MSC-ACE2-EVs had stronger anti-inflammatory, antioxidative stress, and antiapoptotic effects in HK-2 cells subjected to H/R than MSC-NC-EVs. In vivo, MSC-ACE2-EVs could target the injured kidney, reduce blood creatinine and urea nitrogen levels, and protect the kidney from I/R, and this effect may have been related to the activation of the Nrf2/HO-1 signalling pathway CONCLUSION: Taken together, our results demonstrated the anti-inflammatory, antioxidative stress, and antiapoptotic effects of MSC-ACE2-EVs, which protected against I/R injury in vitro and vivo. MSC-ACE2-EVs may be therapeutic agents for RIRI.