Relationship between type 1 diabetes and autoimmune diseases in european populations: A two-sample Mendelian randomization study.

Background: Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Methods: Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions. Results: A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them. Conclusion: Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.

Fast Production of Covalent Organic Frameworks for Covalent Enzyme Immobilization with Boosted Enzymatic Catalysis by Solar-Driven Photothermal Effect.

Developing new enzyme-immobilization systems to stabilize their dynamic structures and meanwhile enhance their catalytic activity is of great significance but very challenging. Herein, we design and fabricate a class of robust mesoporous covalent organic frameworks (COFs) via Michael addition-elimination reaction. It is found that highly crystalline COFs can be produced in 10 min, which is attributed to the promoting effect of the intramolecular hydrogen bond activation. The COFs rich in hydroxyl groups can be facilely post-modified by epibromohydrin to covalently immobilize enzymes with both high loading and activity. Furthermore, we create a solar-driven photothermal-promoted strategy by introducing photoactive azo groups to COF carriers, which can boost the enzyme catalytic performance (lipase) with much higher conversion of various racemic substrates and chiral resolution upon solar light irradiation. The heterogeneous biocatalysts also demonstrate exceptional reusability and stability. This work provides a green and energy-efficient approach to facilitate the scale application of enzyme-immobilized biocatalysts.

The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Can Targeted Protein Degradation Technology Provide a Potential Breakthrough in the Development of Anti-AD Drugs?

Recent advancements in Alzheimer's disease (AD) research have led to the approval of lecanemab and donanemab, highlighting the effectiveness of amyloid-beta (Aß) degradation as a treatment for AD. The prospect of small molecule Aß degraders as a potential treatment, which utilizes emerging targeted protein degradation technology, is exciting, given their ability to address some of the limitations of current therapies and their promising future in AD treatment. Despite facing challenges, these degraders are poised to become a future treatment option, harnessing scientific breakthroughs for more targeted and effective AD therapy.

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

OBJECTIVE: FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism. METHODS: Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis. RESULTS: The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA+HLA-DR+, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment. CONCLUSIONS: We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.

A Knowledge-Data Dual-Driven Framework for Predicting the Molecular Properties of Rechargeable Battery Electrolytes.

Developing rechargeable batteries that operate within a wide temperature range and possess high safety has become necessary with increasing demands. Rapid and accurate assessment of the melting points (MPs), boiling points (BPs), and flash points (FPs) of electrolyte molecules is essential for expediting battery development. Herein, we introduce Knowledge-based electrolyte Property prediction Integration (KPI), a knowledge-data dual-driven framework for molecular property prediction of electrolytes. Initially, the KPI collects molecular structures and properties, and then automatically organizes them into structured datasets. Subsequently, interpretable machine learning further explores the structure-property relationships of molecules from a microscopic perspective. Finally, by embedding the discovered knowledge into property prediction models, the KPI achieved very low mean absolute errors of 10.4, 4.6, and 4.8 K for MP, BP, and FP predictions, respectively. The KPI reached state-of-the-art results in 18 out of 20 datasets. Utilizing molecular neighbor search and high-throughput screening, 15 and 14 promising molecules, with and without Chemical Abstracts Service Registry Number, respectively, were predicted for wide-temperature-range and high-safety batteries. The KPI not only accurately predicts molecular properties and deepens the understanding of structure-property relationships but also serves as an efficient framework for integrating artificial intelligence and  domain knowledge.

Microplastic biofilms promote the horizontal transfer of antibiotic resistance genes in estuarine environments.

As emerging pollutants, microplastics can aggregate microorganisms on their surfaces and form biofilms, enriching antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Consequently, microplastic biofilms have become a focal point of research. Horizontal gene transfer is one of the primary mechanisms by which bacteria acquire antibiotic resistance, with much of the research focusing on suspended bacteria. However, microplastic biofilms, as hotspots for horizontal gene transfer, also merit significant investigation. This study primarily explored and compared the frequency of ARG conjugative transfer between suspended bacteria and microplastic biofilms. The results demonstrated that, compared to suspended bacteria, microplastic biofilms enhanced the frequency of ARG conjugative transfer by 7.2-19.6 times. Among them, biofilms on polyethylene microplastics showed the strongest promotion of conjugation. After the formation of microplastic biofilms, there was a significant increase in bacterial density within the biofilms, which raised the collision frequency of donor and recipient bacteria. Then microplastic biofilms facilitated the gene expression levels of outer membrane proteins, enhanced bacterial gene transfer capabilities, promoted the synthesis of conjugative pili, accelerated the formation of conjugative pairing systems, and elevated the expression levels of genes related to DNA replication and transfer systems, thereby enhancing the conjugative transfer of ARGs within microplastic biofilms. Among different types of microplastic biofilms, polyethylene biofilms exhibited the highest bacterial density, thus showing the highest frequency of ARG conjugation. This study highlights the risks associated with ARG conjugative transfer following the formation of microplastic biofilms and provides insights into the risks of microplastic and antibiotic resistance propagation in estuarine environments.

Partitioned granular sludge coupling with membrane-aerated biofilm reactor for efficient autotrophic nitrogen removal.

The partial nitritation-anammox process based on a membrane-aerated biofilm reactor (MABR) faces several challenges, such as difficulty in suppressing nitrite-oxidizing bacteria (NOB), excessive effluent nitrate, and ineffective synergy between denitrification and anammox bacteria. Therefore, a novel partitioned granular sludge coupling with MABR (G-MABR) was constructed. The chemical oxygen demand (COD) and nitrogen removal efficiency were 88.8 ±â€¯1.8 %-92.6 ±â€¯1.2 % and 88.8 ±â€¯1.5 %-93.6 ±â€¯0.7 %, respectively. The COD was mainly lowered in the lower granular sludge-zone, while nitrogen was removed in the upper MABR-zone. NOB was significantly suppressed in the MABR-zone due to competition for substrate with denitrifying bacteria and anammox bacteria. This partitioned configuration reduced the C/N ratio in the MABR-zone, thus facilitating autotrophic nitrogen removal. Both partial nitrification and denitrification provided nitrite for anammox bacteria in granular sludge, whereas partial nitrification mainly supplied nitrite to the anammox bacteria in membrane biofilms.

Dried Blood Spots Sampling and Population Pharmacokinetic Modeling for Dosing Optimization of Piperacillin in Chinese Neonates.

Piperacillin is commonly used off-label in neonates for the treatment of bacterial infections. This study aimed to assess a dried blood spots (DBS)-based microsampling strategy for supporting population pharmacokinetics and treatment optimization of piperacillin in Chinese neonates. DBS samples from neonatal patients were collected at predefined intervals. Drug blood concentrations were quantified using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was developed using a nonlinear mixed-effects modeling approach. The pharmacokinetic/pharmacodynamics (PK/PD) target was 75% of the time with the unbound drug plasma concentration above the minimum inhibitory concentration (fT>MIC), with a toxicity threshold of unbound drug plasma trough concentration above 64 mg/L. A total of 45 piperacillin samples from 24 neonates were collected. The pharmacokinetics of piperacillin was described using a one-compartment model with postmenstrual age (PMA) as the most significant covariate on clearance. Simulations showed that dosing regimens achieving >90% PK/PD target attainment with <10% risk of possible toxicity were: PMA 33-35 weeks (50 mg/kg q12h), 35-37 weeks (50 mg/kg q8h), and 37-41 weeks (50 mg/kg q6h). In conclusion, Using DBS sampling, we developed a population pharmacokinetic model of piperacillin in Chinese neonates, incorporating PMA to determine optimal dosing regimens.

Self-Polycondensation Flux Synthesis of Ultrastable Olefin-Linked Covalent Organic Frameworks for Electrocatalysis.

Creating new functional materials that efficiently support noble metal catalysts is important and in high demand. Herein, we develop a self-polycondensation flux synthesis strategy that can produce olefin-linked covalent organic framework (COF) platforms with high crystallinity and porosity as the supports of Pd nanoparticles for electrocatalytic nitrogen reduction reaction (ENRR). A series of "two in one" monomers integrating aldehyde and methyl reactive groups are rationally designed to afford COFs with square-shaped pores and ultrahigh chemical stability (e.g., strong acid or alkali environments for >1 month). Functionalizing Fluorine significantly boosts the hydrophobicity of fluoro-functionalized COFs, which can inhibit the competing hydrogen evolution reaction (HER) and enhance ENRR performances. The COFs loading Pd nanoparticles show high NH3 production yields up to 90.0 ± 2.6 µg·h-1·mgcat.-1 and the faradaic efficiency of 44% at -0.2 V versus reversible hydrogen electrode, the best comprehensive performance among all reported COFs. Meanwhile, the catalysts are easy to recover and recycle, as demonstrated by their use for 15 cycles and 17 hours, with good performance retention. This work not only provides a new synthesis strategy for olefin-linked COFs, but also paves a new avenue for the design of highly efficient ENRR catalysts.

Fluorination or Not in Small Molecule Solar Cells: Achieving a Higher Efficiency with Halogen-free End Group.

Fluorination is an efficient strategy for improving organic solar cells (OSCs) efficiency, particularly by fluorinating the end group of emerging nonfullerene acceptors. Here, the fluorination effect was investigated by using small molecule donors with fluorine-free (SBz) and fluorinated (SBz-F) end groups, paired with the emerging nonfullerene acceptor Y6. Interestingly and unexpectedly, fluorination of the end group negatively affects OSCs efficiency, with fluorine-free SBz:Y6 OSCs achieving a higher power conversion efficiency (PCE) of 11.05% compared to the fluorine-containing SBz-F:Y6 blends (PCE = 9.61%). Analysis of space-charge limited currents reveals lower and unbalanced hole/electron mobility in SBz-F:Y6 compared to the SBz:Y6 blends. These findings are further supported by charge recombination dynamics and donor-acceptor miscibility analyses.

Robust Real-time Segmentation of Bio-Morphological Features in Human Cherenkov Imaging during Radiotherapy via Deep Learning.

Cherenkov imaging enables real-time visualization of megavoltage X-ray or electron beam delivery to the patient during Radiation Therapy (RT). Bio-morphological features, such as vasculature, seen in these images are patient-specific signatures that can be used for verification of positioning and motion management that are essential to precise RT treatment. However until now, no concerted analysis of this biological feature-based tracking was utilized because of the slow speed and accuracy of conventional image processing for feature segmentation. This study demonstrated the first deep learning framework for such an application, achieving video frame rate processing. To address the challenge of limited annotation of these features in Cherenkov images, a transfer learning strategy was applied. A fundus photography dataset including 20,529 patch retina images with ground-truth vessel annotation was used to pre-train a ResNet segmentation framework. Subsequently, a small Cherenkov dataset (1,483 images from 212 treatment fractions of 19 breast cancer patients) with known annotated vasculature masks was used to fine-tune the model for accurate segmentation prediction. This deep learning framework achieved consistent and rapid segmentation of Cherenkov-imaged bio-morphological features on another 19 patients, including subcutaneous veins, scars, and pigmented skin. Average segmentation by the model achieved Dice score of 0.85 and required less than 0.7 milliseconds processing time per instance. The model demonstrated outstanding consistency against input image variances and speed compared to conventional manual segmentation methods, laying the foundation for online segmentation in real-time monitoring in a prospective setting.

Multi-Walled Carbon Nanotubes Accelerate Leukaemia Development in a Mouse Model.

Inflammation is associated with an increased risk of developing various cancers in both animals and humans, primarily solid tumors but also myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Multi-walled carbon nanotubes (MWCNTs), a type of carbon nanotubes (CNTs) increasingly used in medical research and other fields, are leading to a rising human exposure. Our study demonstrated that exposing mice to MWCNTs accelerated the progression of spontaneous MOL4070LTR virus-induced leukemia. Additionally, similar exposures elevated pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α and induced reactive oxygen species (ROS) in a murine macrophage cell line. These effects were significantly reduced in immunodeficient mice and when mice were treated with methoxypolyethylene glycol amine (PEG)-modified MWCNTs. These findings underscore the necessity of evaluating the safety of MWCNTs, particularly for those with hematologic cancers.

Camp-style lifestyle modification program (CAMP) for diabetes prevention among rural women with prior GDM: study protocol for a three-arm cluster hybrid type 2 randomized controlled trial.

BACKGROUND: Intensive lifestyle interventions were effective to reduce the risk of type 2 diabetes mellitus (T2DM) for women with gestational diabetes mellitus (GDM) history. However, reaching these mothers and maintaining participation in lifestyle interventions is suboptimal in real-world settings. Effective, feasible and sustainable new lifestyle interventions are needed. The objectives of this three-arm trial are to (1) compare diabetes risk outcomes of an evidence-based intensive lifestyle modification (ILSM) intervention, a camp-style lifestyle modification program (CAMP) intervention, and usual care among women with GDM history; and (2) evaluate the comparative efficacy of the CAMP versus ILSM intervention on implementation outcomes. METHODS: A three-arm cluster randomized clinical trial (RCT) using a hybrid type 2 implementation design will be conducted in two counties in Hunan province in China. Six towns from each county will be randomly selected and assigned to CAMP, ILSM, and the usual care group (25 women from each of 12 towns, 100 women in each arm). The ILSM includes six biweekly in-person sessions and 3-month telephone health consultations, while the CAMP consists of a 2-day camp-based session and 3-month health consultations via a popular social media platform. Both interventions share the same session content, including six lifestyle skills. Efficacy (T2DM risk score and behavioral, anthropometric, psychosocial, and glycemic variables) and implementation outcomes (recruitment, acceptability, feasibility, fidelity, and cost-effectiveness) will be collected at baseline, 6-month, and 12-month. Pre-planned ANOVA F-test and generalized estimating equations will be included to test time-by-arm interactions. DISCUSSION: The CAMP intervention is expected to have better reach, better attendance, and comparable effectiveness in reducing the risk of T2DM, thus improving postpartum care for GDM in China. The delivery of a concentrated format supplemented with technology-based support may provide an efficient and effective delivery model for implementing maternal health promotion programs in primary care settings. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2200058150) on 31st March 2022.

Integrated bioinformatic analysis of protein landscape in gingival crevicular fluid unveils sequential bioprocess in orthodontic tooth movement.

BACKGROUND: The biological mechanisms driving orthodontic tooth movement (OTM) remain incompletely understood. Gingival crevicular fluid (GCF) is an important indicator of the periodontal bioprocess, providing valuable cues for probing the molecular mechanisms of OTM. METHODS: A rigorous review of the clinical studies over the past decade was conducted after registering the protocol with PROSPERO and adhering to inclusion criteria comprising human subjects, specified force magnitudes and force application modes. The thorough screening investigated differentially expressed proteins (DEPs) in GCF associated with OTM. Protein-protein interaction (PPI) analysis was carried out using the STRING database, followed by further refinement through Cytoscape to isolate top hub proteins. RESULTS: A comprehensive summarization of the OTM-related GCF studies was conducted, followed by an in-depth exploration of biomarkers within the GCF. We identified 13 DEPs, including ALP, IL-1ß, IL-6, Leptin, MMP-1, MMP-3, MMP-8, MMP-9, PGE2, TGF-ß1, TNF-α, OPG, RANKL. Bioinformatic analysis spotlighted the top 10 hub proteins and their interactions involved in OTM. Based on these findings, we have proposed a hypothetic diagram for the time-course bioprocess in OTM, which involves three phases containing sequential cellular and molecular components and their interplay network. CONCLUSIONS: This work has further improved our understanding to the bioprocess of OTM, suggesting biomarkers as potential modulating targets to enhance OTM, mitigate adverse effects and support real-time monitoring and personalized orthodontic cycles.

Optical control of butyrylcholinesterase (BChE) activity via photoswitchable azobenzene for potential treatment of Alzheimer's disease.

Photopharmacology is an emerging method in medicinal chemistry to achieve light-controlled drug activity. Azobenzene-based photoswitchable ligands have found widespread application as chemical tools in photopharmacological studies. This study pioneers the design and synthesis of a novel series of photoswitchabled butyrylcholinesterase (BChE) inhibitors, achieved by strategically integrating an azo moiety into an N-benzyl benzamide scaffold. Through a meticulous investigation of the structure-activity relationship (SAR), we discovered that the lead compound, Azo-9, exhibits dynamic cis/trans conformational shifts, dynamically modulating its BChE-binding efficacy. This unique property translates into potential therapeutic benefits, including neuroprotection and cognitive enhancement. Complementary molecular docking simulations underscored the preferential binding of the cis-isomer of Azo-9 to BChE, which was subsequently validated in a glutamate-mediated neuronal injury model. Collectively, Azo-9 emerges as a promising precision tool for Alzheimer's disease (AD) therapy, while also facilitating deeper insights into the disease's underlying mechanisms.

Fruit ripening and postharvest changes in very early-harvested tomatoes.

It is well known that if a fruit is harvested extremely early its development and function are interrupted, and it may never attain full maturity and optimal quality. Reports revealing insights regarding the alterations of maturation, ripening and postharvest quality in very early picked fruits are rare. We examined the effects of early harvesting on tomatoes by characterizing different accessions at the molecular, physiological, and biochemical levels. We found that even very early-harvested fruits could achieve postharvest maturation and ripening though with some defects in pigment and cuticle formation, and seeds from very early-harvested fruits could still germinate and develop as normal and healthy plants. One critical regulator of tomato cuticle integrity, SlCER1-2, was shown to contribute to cuticle defects in very early-harvested fruits. Very early fruit harvest still allowing ripening and seed development indicate that the genetic and physiological programs of later maturation and ripening are set into motion early in fruit development and are not dependent on complete fruit expansion nor attachment to the plant.

Intelligent identification of picking periods of Lu'an Guapian tea by an indicator displacement colorimetric sensor array combined with machine learning.

Lu'an Gua Pian (LAGP) tea is one of the most famous green teas in China. The quality of green tea is related to its picking periods, especially the green tea before Qingming Festival (usually April 6th) is highly praised as precious in the market. In this work, a simple and cheap indicator displacement colorimetric sensor array combined with smartphone was developed to rapidly identify LAGP picked during different picking periods. First, the chemical component contents of LAGP picked before and after Qingming Festival were analyzed. Second, a well-designed colorimetric sensor array was proposed based on the tea component contents differences. Finally, machine learning was used to process the array data taken by a smartphone. By comparison, the accuracy of the best model for the prediction set was 97%. Meanwhile, the multi-channel advantages of the sensing array were demonstrated by an ablation experiment. In addition, the method achieved an AGREE analysis score of 0.88, indicating that it was environmental-friendly.

Role of Enterococcus mundtii in gut of the tomato leaf miner (Tuta absoluta) to detoxification of Chlorantraniliprole.

Chlorantraniliprole (CAP) is applied worldwide for the control of caterpillars (Lepidoptera). However, with the overuse of CAP, the resistance problem in pest control is becoming increasingly serious. Recent studies have indicated a central role of the gut symbiont in insect pest resistance to pesticides and these may apply to the tomato leaf miner Tuta absoluta, is one of the most destructive insects worldwide. Here, we successfully isolated seven strains of tolerant CAP bacterium from the CAP-resistant T. absoluta gut, of which Enterococcus mundtii E14 showed the highest CAP tolerance, with a minimum inhibitory concentration (MIC) of 1.6 g/L and CAP degradation rate of 42.4%. Through transcriptomics and metabolism analysis, we studied the detoxification process of CAP by the E. mundtii E14, and found that CAP can be degraded by E. mundtii E14 into non-toxic compounds, such as 3,4-dihydroxy-2-(5-hydroxy-3,7-dimethylocta-2,6-dien-1-yl) benzoic acid and 2-pyridylacetic acid. Additionally, 2-pyridylacetic acid was detected both intracellular and extracellular in E. mundtii E14 treated with CAP. Meanwhile, we identified 52 up-regulated genes, including those associated with CAP degradation, such as RS11670 and RS19130. Transcriptome results annotated using KEGG indicated significant enrichment in up-regulated genes related to the glyoxylate cycle, nitrogen metabolism, and biosynthesis of secondary metabolites. Additionally, we observed that reinfection with E. mundtii E14 may effectively enhance resistance of T. absoluta to CAP. The LC50 values of the antibiotic treatment population of T. absoluta reinfection with E. mundtii E14 is 0.6122 mg/L, which was 18.27 folds higher than before reinfection. These findings offer new insights into T. absoluta resistance to CAP and contribute to a better understanding of the relationship between insecticide resistance and gut symbionts of T. absoluta, which may play a pivotal role in pest management.

Near-Infrared Fluorescent Probe Reveals Elevated Mitochondrial Viscosity during Acute Alcoholic Liver Injury.

Acute alcoholic liver injury (AALI) has become an important cause of liver disease worldwide, and there is an urgent need to develop noninvasive and sensitive methods to detect and evaluate AALI. We report herein three novel but readily available mitochondrial targeting fluorescence probes (ICR, ICJ, and ICQ) for AALI detection. These probes contain different electron-donating groups, among which ICQ exhibits NIR fluorescence (740 nm), a large Stokes shift (110 nm), and a sensitive response to viscosity (73-fold enhancement in fluorescence from water to glycerol), making it suitable for in vivo imaging. ICQ also exhibits an excellent ability to image mitochondrial viscosity changes in cells. More importantly, ICQ can target the liver selectively and image the viscosity changes in the liver noninvasively. Through establishing an AALI mouse model, ICQ was successfully applied to the in situ imaging changes in liver viscosity during the AALI process. The results showed a significant increase in liver viscosity in AALI mice, indicating that viscosity can serve as a marker for AALI, and ICQ is a promising noninvasive and sensitive tool for detecting and evaluating AALI.