Transfer and fates of damaged mitochondria: role in health and disease.

Intercellular communication is pivotal in mediating the transfer of mitochondria from donor to recipient cells. This process orchestrates various biological functions, including tissue repair, cell proliferation, differentiation and cancer invasion. Typically, dysfunctional and depolarized mitochondria are eliminated through intracellular or extracellular pathways. Nevertheless, increasing evidence suggests that intercellular transfer of damaged mitochondria is associated with the pathogenesis of diverse diseases. This review investigates the prevalent triggers of mitochondrial damage and the underlying mechanisms of mitochondrial transfer, and elucidates the role of directional mitochondrial transfer in both physiological and pathological contexts. Additionally, we propose potential previously unknown mechanisms mediating mitochondrial transfer and explore their prospective roles in disease prevention and therapy.

Two-Dimensional Nonbenzenoid Heteroacene Crystals Synthesized via In-Situ Embedding of Ladder Bipyrazinylenes on Au(111).

Precisely introducing topological defects is an important strategy in nanographene crystal engineering because defects can tune π-electronic structures and control molecular assemblies. The synergistic control of the synthesis and assembly of nanographenes by embedding the topological defects to afford two-dimensional (2D) crystals on surfaces is still a great challenge. By in-situ embedding ladder bipyrazinylene (LBPy) into acene, the narrowest nanographene with zigzag edges, we have achieved the precise preparation of 2D nonbenzenoid heteroacene crystals on Au(111). Through intramolecular electrocyclization of o-diisocyanides and Au adatom-directed [2+2] cycloaddition, the nonbenzenoid heteroacene products are produced with high chemoselectivity, and lead to the molecular 2D assembly via LBPy-derived interlocking hydrogen bonds. Using bond-resolved scanning tunneling microscopy, we determined the atomic structures of the nonbenzenoid heteroacene product and diverse organometallic intermediates. The tunneling spectroscopy measurements revealed the electronic structure of the nonbenzenoid heteroacene, which is supported by density functional theory (DFT) calculations. The observed distinct organometallic intermediates during progression annealing combined with DFT calculations demonstrated that LBPy formation proceeds via electrocyclization of o-diisocyanides, trapping of heteroarynes by Au adatoms, and stepwise elimination of Au adatoms.

Three-dimensional multi-color optical nanoscopy at sub-10-nm resolution based on small-molecule organic probes.

Achieving nanometer-scale resolution remains challenging in expansion microscopy due to photon loss. To address this concern, here we develop a multi-color expansion stimulated emission depletion technique based on small-molecule probes to realize high labeling density and intensity. Our method substantially lowers the barrier to visualizing diverse intracellular proteins and their interactions in three dimensions. It enables us to achieve sub-10-nm resolution in structures such as microfilaments, lysosomes, and mitochondria, providing new insights into cell biology.

[Distribution, Respiratory Exposure, and Traceability of Atmospheric Microplastics in Yichang City].

As an emerging environmental pollutant, microplastics have attracted much attention, but the sources and health hazards of atmospheric microplastics (AMPs) remain unclear. In order to explore the distribution characteristics, assess the risk of human respiratory exposure, and analyze the sources of AMPs in different functional areas of Yichang City, AMPs samples from 16 observation points were collected and analyzed, and the HYSPLIT model was used. The results showed that the main shapes of AMPs in Yichang City were fiber, fragment, and film, and six colors were observed including transparent, red, black, green, yellow, and purple. The smallest size was 10.42 µm, and the largest was 4761.42 µm. The deposition flux of AMPs was (4400±474) n·(m2·d)-1. The types of APMs were polyester fiber (PET), acrylonitrile-butadiene-styrene copolymer (ABS), polyamide (PA), rubber (Rubber), polyethylene (PE), cellulose acetate (CA), and polyacrylonitrile (PAN). The order of the subsidence flux in each functional area was as follows:urban residential area>agricultural production area>landfill>chemical industrial park>town residential area. The human respiratory exposure risk assessment models showed that the daily intake of AMPs (EDI) for adults and children in urban residential areas was higher than in town residential areas. The atmospheric backward trajectory simulation showed that the AMPs in the districts and counties of Yichang City mainly came from the surrounding areas via short-distance transportation. This study provided basic data support for the research on AMPs in the middle reaches of the Yangtze River and was of great significance for the traceability and health risk research of AMPs pollution.

High-speed spatially re-modulated structured illumination microscopy.

Structured illumination microscopy (SIM) allows non-invasive visualization of nanoscale subcellular structures. However, image acquisition and reconstruction become the bottleneck to further improve the imaging speed. Here, we propose a method to accelerate SIM imaging by combining the spatial re-modulation principle with Fourier domain filtering and using measured illumination patterns. This approach enables high-speed, high-quality imaging of dense subcellular structures using a conventional nine-frame SIM modality without phase estimation of the patterns. In addition, seven-frame SIM reconstruction and additional hardware acceleration further improve the imaging speed using our method. Furthermore, our method is also applicable to other spatially uncorrelated illumination patterns, such as distorted sinusoidal, multifocal, and speckle patterns.

Association of geriatric nutritional risk index with all-cause hospital mortality among elderly patients in intensive care unit.

Background: Malnutrition is associated with poor outcomes for geriatric patients in intensive care unit (ICU). It is important to identify patients at risk of malnutrition and provide individual nutrition support. The assessment of malnutrition risk is not easy for these patients due to their cognitive impairment. Geriatric nutrition risk index (GNRI) is a simple and objective scoring tool to evaluate the risk of malnutrition in elderly patients. In this study, we aimed to see whether GNRI score was appropriate to predict clinical outcomes among geriatric patients in the setting of ICU. Materials and methods: Elderly patients with age ≥ 65 years were extracted from Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Categories based on GNRI were classified as major risk (GNRI <82), moderate risk (GNRI 82 to <92), low risk (GNRI 92 to ≤98), and no risk (GNRI >98). The primary outcome was all-cause hospital mortality. Multivariable Cox proportional hazards regression models and restricted cubic spline were used to investigate associations of GNRI with hospital mortality, respectively. A two-piecewise linear regression model was applied to examine the inflection point of GNRI on hospital mortality. To reduce selection bias, propensity score matching (PSM) was used in a 1:1 ratio. Results: A total of 3,696 geriatric patients were finally included with median age 75 (69, 81) years. The prevalence of major risk was 28.6%. In the fully adjusted model, GNRI categories featured a negative trend with hospital mortality (p for trend = 0.037). Restricted cubic spline analysis demonstrated an L-shaped relationship between GNRI and hospital mortality before and after matching. The inflection point was 78.7. At the left side of inflection point, GNRI levels were significantly negatively associated with hospital mortality (HR = 0.96, 95% CI: 0.94-0.98; p < 0.001) and featured no significant relations at the right side. Multiple linear regression also showed that GNRI was negatively associated with length of stay in hospital. Conclusion: The major risk of malnutrition defined by GNRI was able to predict poor prognosis for geriatric patients admitted to ICU.

Role of VPS39, a key tethering protein for endolysosomal trafficking and mitochondria-lysosome crosstalk, in health and disease.

The coordinated interaction between mitochondria and lysosomes, mainly manifested by mitophagy, mitochondria-derived vesicles, and direct physical contact, is essential for maintaining cellular life activities. The VPS39 subunit of the homotypic fusion and protein sorting complex could play a key role in the regulation of organelle dynamics, such as endolysosomal trafficking and mitochondria-vacuole/lysosome crosstalk, thus contributing to a variety of physiological functions. The abnormalities of VPS39 and related subunits have been reported to be involved in the pathological process of some diseases. Here, we analyze the potential mechanisms and the existing problems of VPS39 in regulating organelle dynamics, which, in turn, regulate physiological functions and disease pathogenesis, so as to provide new clues for facilitating the discovery of therapeutic targets for mitochondrial and lysosomal diseases.

Target and suspect screening of pesticide residues in soil samples from peach orchards using liquid chromatography quadrupole time-of-flight mass spectrometry.

Agricultural soil contamination by pesticide residues has become a serious issue of increasing concern due to their high persistence and toxicity to non-target species. However, as the world's largest peach producer, national scale surveys on pesticide residues in peach orchard soils are scarce in China. In this study, a target and suspect screening method covering over 200 pesticides commonly used in peach orchards was developed using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry in MSE. An identification strategy using different data processing parameters was developed to identify the pesticide occurrence in soil. The method was applied to soil samples from typical peach orchards in 12 regions across China. The present work also discusses in detail the frequency of occurrence, concentration of pesticides, spatial distribution of multiresidues, and relationship between pesticide occurrence and soil properties. In the tested soil samples, 21 herbicides (level 1), 31 fungicides (level 2a), 24 insecticides (level 2a), and 3 growth regulators (level 2a) were identified. The total concentrations of quantifiable herbicides in the soil samples ranged from 1.05 to 327 ng/g. Only in 5.4% of the soil samples, no pesticide residues were present. By contrast, more than 86% of the total contained multiple residues. This study represents the first large-scale survey of pesticides in soil from peach orchards and provides comprehensive and accurate information on the pesticide residue status for risk assessment.

Global Research Activities on Micro(nano)plastic Toxicity to Earthworms.

Micro(nano)plastics are emerging contaminants that have been shown to cause various ecotoxicological effects on soil biota. Earthworms, as engineers of the ecosystem, play a fundamental role in soil ecosystem processes and have been used as model species in ecotoxicological studies. Research that evaluates micro(nano)plastic toxicity to earthworms has increased greatly over the last decade; however, only few studies have been conducted to highlight the current knowledge and evolving trends of this topic. This study aims to visualize the research status and knowledge structure of the relevant literature. Bibliometrics and visualization analyses were conducted using co-citations, cooperation networks and cluster analysis. The results showed that micro(nano)plastic toxicity to earthworms is an emerging and increasingly popular topic, with 78 articles published from 2013 to 2022, the majority of which were published in the last two years. The most prolific publications and journals involved in this topic were also identified. In addition, the diversity of cooperative relationships among different countries and institutions confirmed the evolution of this research field, in which China contributed substantially. The high-frequency keywords were then determined using co-occurrence analysis, and were identified as exposure, bioaccumulation, soil, pollution, toxicity, oxidative stress, heavy metal, microplastic, Eisenia foetida and community. Moreover, a total of eight clusters were obtained based on topic knowledge clustering, and these included the following themes: plastic pollution, ingestion, combined effects and the biological endpoints of earthworms and toxic mechanisms. This study provides an overview and knowledge structure of micro(nano)plastic toxicity to earthworms so that future researchers can identify their research topics and potential collaborators.

An enzyme-free, ultrasensitive strategy for simultaneous screening of the p-nitrophenyl substituent organophosphorus pesticides.

An enzyme-free, sensitive, and convenient approach was reported for the P-nitrophenyl substituent organophosphorus pesticides (NSOPs) of paraoxon-methyl (PM), paraoxon-ethyl (PE), parathion-methyl (PTM) and parathion-ethyl (PTE)) by indirectly quantification of the 4-nitrophenol (4-NP, hydrolysis product of the NSOPs). NaOH instead of hydrolase/nanozyme was applied, and temperature, pH, ultrasound was investigated to improve the NSOPs hydrolysis. Under the optimized conditions, the hydrolysis efficiencies were up to 99.9 %, 99.9 %, 99.6 %, 96.0 % for PM (10 min), PE (30 min), PTM (90 min) and PTE (120 min), based on which a low detection limits of 0.06 (PM), 0.07 (PE), 0.06 (PTM) and 0.07 (PTE) ppb were calculated with the 4-NP detection limit (0.03 ppb). Furthermore, the method exhibited good performance for the NSOPs with recoveries from 88.87 % to 100.33 % in real samples. This indirect approach offered an ultrasensitive alternative for the NSOPs detection, which holds great potential in practical application for the assessment of food safety and environmental risks.

Enhanced axial resolution of lattice light sheet microscopy by fluorescence differential detection.

Lattice light-sheet microscopy (LLSM) is promising in long-term biological volumetric imaging due to its high spatiotemporal resolution and low phototoxicity. However, three-dimensional (3D) isotropic spatial resolution remains an unmet goal in LLSM because of its poorer axial resolution. Combing LLSM with fluorescence differential detection, namely LLSDM, has been proposed to improve the axial resolution of LLSM in simulation. It demonstrates the possibility of further enhancing the axial resolution in 3D volumetric imaging with LLSM by specifically discarding the off-focus photons captured using a complementary optical lattice (OL) profile generated with additional 0-π phase modulation at the objective pupil plane. The direct generation of the complementary lattice profile using the binary phase modulator conjugated to the sample plane for amplitude modulation, as used in LLSM, is also permittable. Nevertheless, the previously proposed configuration fails to provide a symmetric complementary lattice pattern along the axial axis, thus leading to the imbalanced off-focus photon suppression in the reconstructed images after subtraction [Opt. Lett.45, 2854 (2020)10.1364/OL.393378]. Here, we modified the LLSDM theory which can produce an ideal complementary lattice pattern with central zero intensity and symmetrically distributed sidelobes. We also analyzed the impact of numerical aperture matching between the original and complementary lattice patterns and presented the consistency between the simulated and experimental results. As demonstrated by imaging the distribution of fluorescent beads and microtubules in fixed U2OS cells, as well as the dynamics of filopodia in live U2OS cells, LLSDM provides about 1.5 times improvement in axial resolution, and higher imaging contrast compared with traditional LLSM.

Ginseng and ginsenosides: Therapeutic potential for sarcopenia.

Sarcopenia is a progressive syndrome that results in a decline in skeletal muscle mass and strength. This affects patients' quality of life and increases the risk of falls and fractures, particularly among the elderly. With the aging of the population and the increasing number of patients with modern chronic diseases, the prevalence and complications of sarcopenia have increased, involving Akt-mediated signaling pathways, mitochondrial activity, satellite cell differentiation, inflammation and so on. Ginseng is a traditional herb medicine with extremely high medicinal value and possesses multiple pharmacological effects. This article summarizes such impacts of ginseng extracts and active ingredients on sarcopenia, and analyzes their related signaling pathways, so as to provide a reference for future research regarding the application of ginseng and ginsenosides as a potential therapy for sarcopenia.

MiR-30a-3p Targeting FLT1 Modulates Trophoblast Cell Proliferation in the Pathogenesis of Preeclampsia.

Preeclampsia (PE) may pose significant adverse effects on pregnant women. Dysregulation of angiogenesis, trophoblast invasion, and proliferation are known to be associated with PE development and progression. Fms related tyrosine kinase 1 (FLT1), an anti-angiogenic factor, is consistently upregulated in PE patients. Recent papers highlight that aberrant miR-30a-3p expression contributes to PE development. More effects are needed to assess the biological function of placental miR-30a-3p in PE. The soluble FLT1 (sFLT1) and FLT1 levels were tested by ELISA assay and Western blotting assay. mRNA levels were measured by RT-qPCR assay. Colony formation and MTT assays were applied to assess the effect of miR-30a-3p on trophoblast cell proliferation. The serum sFLT1 and placental FLT1 levels were substantially high in patients with PE. Using miRNA microarray assay, we identified miR-30a-3p upregulation in PE patients' placenta tissues. We further confirmed that miR-30a-3p binds to the 3'-UTR of FLT1 gene and positively regulate its expression. Forcing miR-30a-3p expression inhibited trophoblast cell proliferation and vice versa. In conclusion, persistent high levels of FLT1 and miR-30a-3p may pose adverse effects on angiogenesis and trophoblast proliferation in placenta of PE patients. Therefore, targeting FLT1 and miR-30a-3p may serve as ideal strategies for managing patients with PE.

Development and applications of diffusive gradients in thin films for monitoring pharmaceuticals in surface waters.

Pharmaceutical contaminants in surface water have raised significant concerns because of their potential ecological risks. In particular, coronavirus disease 2019 (COVID-19)-related pharmaceuticals can be released to surface water and reduce environmental water quality. Therefore, reliable and robust sampling tools are required for monitoring pharmaceuticals. In this study, passive sampling devices of diffusive gradients in thin films (DGTs) were developed for sampling 35 pharmaceuticals in surface waters. The results demonstrated that hydrophilic-lipophilic balance (HLB) was more suitable for DGT-based devices compared with XAD18 and XDA1 resins. For most pharmaceuticals, the performance of the HLB-DGT devices were independent of pH (5.0-9.0), ionic strength (0.001-0.5 M), and flow velocity (0-400 rpm). The HLB-DGT devices exhibited linear pharmaceutical accumulation for 7 days, and time-weighted average concentrations provided by the HLB-DGT were comparable to those measured by conventional grab sampling. Compared to previous studies, we extended DGT monitoring to include three antiviral drugs used for COVID-19 treatment, which may inspire further exploration on identifying the effects of COVID-19 on ecological and human health.

Dairy Trade Helps to Alleviate Global Carbon Emission Pressure.

Global dairy production, consumption, and trade are growing rapidly, driven by population and per capita income growth and increasing health concerns mainly from developing countries, which has aroused concerns about the related carbon emission (mostly in the form of methane) increase. If all of the dairy products consumed were produced locally/domestically in the developing countries/economies (a counterfactual scenario), the carbon emissions in 2018 would be 28 Mt CO2-equiv higher than its status quo (a factual scenario). The present study indicates that unlike in many global trade cases in which carbon leakages are from developed to developing countries, global dairy trade is characterized by net embodied carbon flows from developed to developing countries/economies due to the fact that there is an overwhelming one-way-flow of dairy products from developed to developing countries/economies. The differences in the carbon emission factors between the developed and developing countries/economies provide an opportunity that global dairy trade and production specialization can help to reduce carbon emissions from increasing dairy product demand, and the total reduction potential is estimated to be about 414 Mt CO2-equiv from 2018 to 2030. Free trade agreements such as the Regional Comprehensive Economic Partnership will incentivize larger carbon emission reduction benefits through promoting dairy trade.

Development and validation of a prognostic nomogram among patients with acute exacerbation of chronic obstructive pulmonary disease in intensive care unit.

BACKGROUND: Acute exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) contributes significantly to mortality among patients with COPD in Intensive care unit (ICU). This study aimed to develop a nomogram to predict 30-day mortality among AECOPD patients in ICU. METHODS: In this retrospective cohort study, we extracted AECOPD patients from Medical Information Mart for Intensive Care III (MIMIC-III) database. Multivariate logistic regression based on Akaike information criterion (AIC) was used to establish the nomogram. Internal validation was performed by a bootstrap resampling approach with 1000 replications. The discrimination and calibration of the nomogram were evaluated by Harrell's concordance index (C-index) and Hosmer-Lemeshow (HL) goodness-of-fit test. Decision curve analysis (DCA) was performed to evaluate its clinical application. RESULTS: A total of 494 patients were finally included in the study with a mean age of 70.8 years old. 417 (84.4%) patients were in the survivor group and 77 (15.6%) patients were in the non-survivor group. Multivariate logistic regression analysis based on AIC included age, pO2, neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), invasive mechanical ventilation and vasopressor use to construct the nomogram. The adjusted C-index was 0.745 (0.712, 0.778) with good calibration (HL test, P = 0.147). The Kaplan-Meier survival curves revealed a significantly lower survival probability in the high-risk group than that in the low-risk group (P < 0.001). DCA showed that nomogram was clinically useful. CONCLUSION: The nomogram developed in this study could help clinicians to stratify AECOPD patients and provide appropriate care in clinical setting.

Species-dependent response of food crops to polystyrene nanoplastics and microplastics.

This study investigated the early responses of four common food crops (Italian lettuce, radish, wheat and corn) by exposing their seeds to suspensions of polystyrene nanoparticles (nano-PS) and microspheres (micro-PS). We found that the crop responses to exposure to nano-PS and micro-PS at different doses were dependent on the plant species. Among the four species, Italian lettuce was the most sensitive crop in terms of seed germination and its germination index after polystyrene exposure for 7 days was inhibited by 18.2%-36.0% compared with that of the control (p < 0.05). The root growth (root dry weight, root/shoot ratio and root length) of Italian lettuce and corn was significantly inhibited by the exposure treatment (p < 0.05), whereas that of radish and wheat was hardly affected. Analyses of antioxidant enzymatic activities, lipid peroxidation, and integrated biomarker indexes confirmed that the toxic effects of nano-PS and micro-PS on crops are likely due to oxidative stress. The observed distribution of fluorescent nano-PS in the roots or germs of the tested crops suggests that nanoplastics can be taken up by plants even at a very early growth stage (<7 days after sowing). Future research is needed in order to obtain more insights into their implications for agricultural sustainability and food safety.

Co-occurrence of antiseptic triclocarban and chiral anti-inflammatory ibuprofen in environment: Association between biological effect in sediment and risk to human health.

Residues of antiseptics and drugs have been ubiquitously detected in aquatic water-sediment systems, and are thus considered emerging contaminants that threaten our global environment. To investigate the potential risk of ibuprofen and triclocarban in sediment, effects of enzyme activity on the enantioselective degradation in sediment were investigated. Enantioselective fate of rac-ibuprofen was observed in sediment with R-enantiomer exhibiting preferential degradation. Enzyme evidence showed that high levels of triclocarban could significantly inhibit activities of catalase and urease activities in sediment, as well as increase the half-life of ibuprofen (from 5.8 d to 10.1 d). Cytotoxicity data suggested that cell growth processes were significantly affected by ibuprofen and triclocarban co-exposure, which was consistent with apoptosis results. Additionally, the expression of several proteins (Cyto-c, Nrf2, p62, Keap1, NQO1, and Pink1) were markedly induced upon exposure to ibuprofen in the presence of triclocarban. In conclusion, these findings illustrated that co-occurrence of ibuprofen and triclocarban residues have synergistic adverse effects to the environment and synergistically threaten human health.

Strong sorption of two fungicides onto biodegradable microplastics with emphasis on the negligible role of environmental factors.

Microplastics have attracted much attention in recent years because they are able to interact with other pollutants including pesticides, with implications for the potential risks to biota. However, the sorption behavior of pesticides on microplastics, especially on biodegradable microplastics which are promising alternatives to conventional polymers, has been insufficiently studied. In this study, triadimefon and difenoconazole were selected as model triazole fungicides, and their sorption behavior on a typical biodegradable microplastics (PBS: polybutylene succinate) and two conventional polyethylene (PE) and polyvinyl chloride (PVC) microplastics was investigated with batch experiments in an aqueous solution. PBS presented the highest sorption capacity for triadimefon (104.2 ± 4.8 µg g-1) and difenoconazole (192.8 ± 2.3 µg g-1), which was 1.8- and 1.3-fold that on PE and 4.4- and 7.4-fold that of PVC, respectively. The results of sorption kinetic and isotherm modeling were better fit by a pseudo-second order model and linear model, respectively. More importantly, the effects of environmental factors (pH, salinity and dissolved organic matter) on the sorption behavior were investigated. Fungicide sorption on PBS was generally not affected by salinity, pH or dissolved organic matter. However, in contrast, salinity and dissolved organic matter both significantly decreased sorption on PE and PVC. The results showed that not only the sorption capacities of biodegradable microplastics but also their responses to environmental factors are quite different from those of conventional microplastics. This finding highlights the importance of the role played by biodegradable microplastics in the accumulation and transportation of organic pollutants.

ß-cyclodextrin improve the tolerant of freshwater algal Spiny Scenedesmus to chiral drugs venlafaxine and its metabolite.

This study based on the freshwater algae Spiny scenedesmus (S. scenedesmus) with tolerance to venlafaxine aiming to investigate algae removal abilities. Here presented for the first time to evaluate the effect of ß-cyclodextrin (ß-CD) on reduce toxicity and enhance removal ability of venlafaxine and O-desmethylvenlafaxine to S. scenedesmus. Based on dose-response results, the toxicity of R-venlafaxine (EC50 = 6.81 mg·L -1) and R-O-desmethylvenlafaxine (EC50 = 3.36 mg·L -1) to algae were more than two times than those in the presence of ß-CD treatment (10.64 mg L -1 for R-venlafaxine and 11.87 mg L -1 for R-O-desmethylvenlafaxine). The significant differences were observed between S-venlafaxine (11.07 mg L -1) and S-O-desmethylvenlafaxine (10.24 mg L -1), which were more toxic than R-forms. The half-lives of R- and S-venlafaxine were 0.8 d and 0.5 d in the presence of ß-CD, which were obvious shorter than those in alone treatments. In addition, our experiments not only demonstrated that ß-CD performed particularly well for removal of venlafaxine and O-desmethylvenlafaxine, it significantly reduces the toxicity of venlafaxine to alga. These results highlight advantages of ß-CD relevant to chiral drugs removal and protection of aquatic organisms, which may have a better application for environmental and ecological safety in future.