Peripheral Ganglion Cell Complex Thickness and Retinal Microvasculature in Myopia Using Wide-Field Swept-Source OCT.

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Using -NH and -OH rich organic cathodes to explore proton transport in aqueous zinc-ion batteries.

An organic cathode material for zinc-ion batteries shows a reliable proton transport mechanism. It uses a pyrazine ring as the energy storage unit and H+ as the shuttle ion, enabling high functionality utilization with rapid redox kinetics.

Progression Patterns and Risk Factors of Axial Elongation in Young Adults with Non-Pathologic High Myopia: Three-year Large Longitudinal Cohort Follow-up.

PURPOSE: To investigate the progression patterns and risk factors of axial elongation in young adults with non-pathologic high myopia. DESIGN: Prospective, clinical observational cohort study with 2- to 4-year follow-up. METHODS: A total of 1043 eyes of 563 participants (3515 medical records) aged 18 to 50 years with non-pathologic high myopia (axial length [AL] ≥ 26 mm; myopic maculopathy < diffuse chorioretinal atrophy; without posterior staphyloma) were included from 1546 participants (6318 medical records). Annual axial elongation was calculated via linear mixed-effect models. The associated risk factors of axial elongation were determined by ordinal logistic regression analysis, with generalized estimate equations for eliminating an interocular correlation bias. RESULTS: Based on 5359 times of AL measurements, the annual axial elongation of participants (mean [SD] age 31.39 [9.22] years) was 0.03 mm/year (95% confidence interval [CI], 0.03-0.04, P < 0.001) during a 30.23 (6.06) months' follow-up. Severe (> 0.1 mm/year), moderate (0.05-0.09 mm/year), mild (0-0.049 mm/year), and nil (≤ 0 mm/year) elongation was observed in 122 (11.7%), 211 (20.2%), 417 (40.0%), and 293 (28.1%) eyes. The following risk factors were significantly associated with axial elongation: baseline AL≥ 28 mm (odds ratio [OR], 4.23; 95%CI, 2.95-6.06; P < 0.001); age < 40 years (OR, 1.64; 95%CI, 1.18-2.28; P = 0.003); axial asymmetry (OR, 2.04; 95%CI, 1.26-3.29; P = 0.003), and women (OR, 1.52; 95%CI, 1.13-2.2.05; P = 0.006). Using anti-glaucoma medications was a protective factor (OR, 0.46; 95%CI, 0.27-0.79; P = 0.005), which slowed 75% of axial elongation from 0.04 (0.06) to 0.01 (0.06) mm/y (P < 0.001). CONCLUSIONS: Axial elongation continued in young adults with non-pathologic myopia. Risk factors included longer baseline AL and axial asymmetry, younger age, and woman. Topical use of anti-glaucoma medications may be useful to reduce ongoing axial elongation.

Double-edged sword effects of sulfate reduction process in sulfur autotrophic denitrification system: Accelerating nitrogen removal and promoting antibiotic resistance genes spread.

This study proposed the double-edged sword effects of sulfate reduction process on nitrogen removal and antibiotic resistance genes (ARGs) transmission in sulfur autotrophic denitrification system. Excitation-emission matrix-parallel factor analysis identified the protein-like fraction in soluble microbial products as main endogenous organic matter driving the sulfate reduction process. The resultant sulfide tended to serve as bacterial modulators, augmenting electron transfer processes and mitigating oxidative stress, thereby enhancing sulfur oxidizing bacteria (SOB) activity, rather than extra electron donors. The cooperation between SOB and heterotroph (sulfate reducing bacteria (SRB) and heterotrophic denitrification bacteria (HDB)) were responsible for advanced nitrogen removal, facilitated by multiple metabolic pathways including denitrification, sulfur oxidation, and sulfate reduction. However, SRB and HDB were potential ARGs hosts and assimilatory sulfate reduction pathway positively contributed to ARGs spread. Overall, the sulfate reduction process in sulfur autotrophic denitrification system boosted nitrogen removal process, but also increased the risk of ARGs transmission.

Application of Machine Learning in Nanotoxicology: A Critical Review and Perspective.

The massive production and application of nanomaterials (NMs) have raised concerns about the potential adverse effects of NMs on human health and the environment. Evaluating the adverse effects of NMs by laboratory methods is expensive, time-consuming, and often fails to keep pace with the invention of new materials. Therefore, in silico methods that utilize machine learning techniques to predict the toxicity potentials of NMs are a promising alternative approach if regulatory confidence in them can be enhanced. Previous reviews and regulatory OECD guidance documents have discussed in detail how to build an in silico predictive model for NMs. Nevertheless, there is still room for improvement in addressing the ways to enhance the model representativeness and performance from different angles, such as data set curation, descriptor selection, task type (classification/regression), algorithm choice, and model evaluation (internal and external validation, applicability domain, and mechanistic interpretation, which is key to ensuring stakeholder confidence). This review explores how to build better predictive models; the current state of the art is analyzed via a statistical evaluation of literature, while the challenges faced and future perspectives are summarized. Moreover, a recommended workflow and best practices are provided to help in developing more predictive, reliable, and interpretable models that can assist risk assessment as well as safe-by-design development of NMs.

Optimal operation of energy-intensive load considering electricity carbon market.

Energy-intensive load benefits from low electricity tariff and carbon emission, since they occupy certain amounts in the total cost of the product. This paper considers energy-intensive load participation in the electricity as well as carbon trading to reduce the cost. Firstly, an electricity-carbon model is established based on the correlation value method to calculate the carbon emissions of energy-intensive load based on their electricity consumption to realize the carbon amount. Afterwards, the baseline method is used to allocate free carbon emission quotas to energy-intensive load and a reward-penalty carbon trading price mechanism considering offset is proposed. Next, the objective function to achieve maximum benefits, and to reduce output fluctuation, and to improve new energy accommodation is proposed. The case studies show that, by comparing multi-objective function optimization, the optimization target proposed in this paper can effectively reduce wind power output fluctuations and improve wind power accommodation. Through the total participation in carbon trading and electricity market income, multi-objective optimization can increase the system income while ensuring that energy-intensive load meets production requirements under the premise of reducing carbon emissions, verifying the effectiveness of the low-carbon optimal operation model proposed in this paper.

Deterministic grayscale nanotopography to engineer mobilities in strained MoS2 FETs.

Field-effect transistors (FETs) based on two-dimensional materials (2DMs) with atomically thin channels have emerged as a promising platform for beyond-silicon electronics. However, low carrier mobility in 2DM transistors driven by phonon scattering remains a critical challenge. To address this issue, we propose the controlled introduction of localized tensile strain as an effective means to inhibit electron-phonon scattering in 2DM. Strain is achieved by conformally adhering the 2DM via van der Waals forces to a dielectric layer previously nanoengineered with a gray-tone topography. Our results show that monolayer MoS2 FETs under tensile strain achieve an 8-fold increase in on-state current, reaching mobilities of 185 cm²/Vs at room temperature, in good agreement with theoretical calculations. The present work on nanotopographic grayscale surface engineering and the use of high-quality dielectric materials has the potential to find application in the nanofabrication of photonic and nanoelectronic devices.

The U1 small nuclear RNA enhances drought tolerance in Arabidopsis.

Alternative splicing (AS) is an important post-transcriptional regulatory mechanism that improves plant tolerance to drought stress by modulating gene expression and generating proteome diversity. The interaction between the 5' end of U1 small nuclear RNA (U1 snRNA) and the conserved 5' splice site of precursor messenger RNA (pre-mRNA) is pivotal for U1 snRNP involvement in AS. However, the roles of U1 snRNA in drought stress responses remain unclear. This study provides a comprehensive analysis of AtU1 snRNA in Arabidopsis (Arabidopsis thaliana), revealing its high conservation at the 5' end and a distinctive four-leaf clover structure. AtU1 snRNA is localized in the nucleus and expressed in various tissues, with prominent expression in young floral buds, flowers, and siliques. Overexpression of AtU1 snRNA confers enhanced abiotic stress tolerance, as evidenced in seedlings by longer seedling primary root length, increased fresh weight, and a higher greening rate compared to the wild type. Mature AtU1 snRNA overexpressor plants exhibit higher survival rates and lower water loss rates under drought stress, accompanied by a significant decrease in H2O2 and increase in proline. This study also provides evidence of altered expression levels of drought-related genes in AtU1 snRNA overexpressor or genome-edited lines, reinforcing the crucial role of AtU1 snRNA in drought stress responses. Furthermore, the overexpression of AtU1 snRNA influences the splicing of downstream target genes, with a notable impact on SPEECHLESS (SPCH), a gene associated with stomatal development, potentially explaining the observed decrease in stomatal aperture and density. These findings elucidate the critical role of U1 snRNA as an AS regulator in enhancing drought stress tolerance in plants, contributing to a deeper understanding of the AS pathway in drought tolerance and increasing awareness of the molecular network governing drought tolerance in plants.

Anthropogenic impacts on polycyclic aromatic hydrocarbons in surface water: Evidence from the COVID-19 lockdown.

The lockdown restrictions against coronavirus disease 2019 (COVID-19) have led to unprecedented reductions in global anthropogenic activities. Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic combustion-induced pollutants, but the influence of anthropogenic responses to COVID-19 on PAH contamination remains largely unknown. Here we quantified the impacts of lockdown restrictions on 16PAH pollution based on the data in concentrations dissolved in the water phase and absorbed on the suspended particulate matter (SPM) in the Elbe River from 2015 to 2021 and determined the changes in source contributions classified by individual years and stations. Results show that the annual average PAH concentrations in water and SPM were determined as 0.055 µg·L-1 and 3.77 mg·kg-1 from 2015 to 2021, respectively. Pronounced declines in PAH on SPM (up to -18 %) were observed during the three lockdowns in Germany from 2020 to 2021. However, dramatic rebounds of anthropogenic activities during the removal of the lockdown led to increases (up to 29 %) in ∑16PAH concentrations compared to the same period in previous years. Through the source apportionment method, vehicle and coal emissions were the two most predominant sources of PAHs in the river. Vehicle contribution decreased during the lockdown, while coal emissions increased by 5 %. Health risks for three age groups were assessed as potential low risk and decreased by 18 % from 1.54 × 10-4 in 2015 to 1.27 × 10-4 in 2019, and rebounded to 1.40 × 10-4 in 2020-2021. The findings of this study highlight the strong consistency between PAH concentrations and anthropogenic intensity, implying that source control from improved cleaner production is an effective pathway for mitigating PAH contamination in the aquatic environment.

A novel LGALS1-depended and immune-associated fatty acid metabolism risk model in acute myeloid leukemia stem cells.

Leukemia stem cells (LSCs) are recognized as the root cause of leukemia initiation, relapse, and drug resistance. Lipid species are highly abundant and essential component of human cells, which often changed in tumor microenvironment. LSCs remodel lipid metabolism to sustain the stemness. However, there is no useful lipid related biomarker has been approved for clinical practice in AML prediction and treatment. Here, we constructed and verified fatty acid metabolism-related risk score (LFMRS) model based on TCGA database via a series of bioinformatics analysis, univariate COX regression analysis, and multivariate COX regression analysis, and found that the LFMRS model could be an independent risk factor and predict the survival time of AML patients combined with age. Moreover, we revealed that Galectin-1 (LGALS1, the key gene of LFMRS) was highly expressed in LSCs and associated with poor prognosis of AML patients, and LGALS1 repression inhibited AML cell and LSC proliferation, enhanced cell apoptosis, and decreased lipid accumulation in vitro. LGALS1 repression curbed AML progression, lipid accumulation, and CD8+ T and NK cell counts in vivo. Our study sheds light on the roles of LFMRS (especially LGALS1) model in AML, and provides information that may help clinicians improve patient prognosis and develop personalized treatment regimens for AML.

A Novel Simulation Method for 3D Digital-Image Correlation: Combining Virtual Stereo Vision and Image Super-Resolution Reconstruction.

3D digital-image correlation (3D-DIC) is a non-contact optical technique for full-field shape, displacement, and deformation measurement. Given the high experimental hardware costs associated with 3D-DIC, the development of high-fidelity 3D-DIC simulations holds significant value. However, existing research on 3D-DIC simulation was mainly carried out through the generation of random speckle images. This study innovatively proposes a complete 3D-DIC simulation method involving optical simulation and mechanical simulation and integrating 3D-DIC, virtual stereo vision, and image super-resolution reconstruction technology. Virtual stereo vision can reduce hardware costs and eliminate camera-synchronization errors. Image super-resolution reconstruction can compensate for the decrease in precision caused by image-resolution loss. An array of software tools such as ANSYS SPEOS 2024R1, ZEMAX 2024R1, MECHANICAL 2024R1, and MULTIDIC v1.1.0 are used to implement this simulation. Measurement systems based on stereo vision and virtual stereo vision were built and tested for use in 3D-DIC. The results of the simulation experiment show that when the synchronization error of the basic stereo-vision system (BSS) is within 10-3 time steps, the reconstruction error is within 0.005 mm and the accuracy of the virtual stereo-vision system is between the BSS's synchronization error of 10-7 and 10-6 time steps. In addition, after image super-resolution reconstruction technology is applied, the reconstruction error will be reduced to within 0.002 mm. The simulation method proposed in this study can provide a novel research path for existing researchers in the field while also offering the opportunity for researchers without access to costly hardware to participate in related research.

Wide-Band Unambiguous Quantum Sensing via Geodesic Evolution.

We present a quantum sensing technique that utilizes a sequence of π pulses to cyclically drive the qubit dynamics along a geodesic path of adiabatic evolution. This approach effectively suppresses the effects of both decoherence noise and control errors while simultaneously removing unwanted resonance terms, such as higher harmonics and spurious responses commonly encountered in dynamical decoupling control. As a result, our technique offers robust, wide-band, unambiguous, and high-resolution quantum sensing capabilities for signal detection and individual addressing of quantum systems, including spins. To demonstrate its versatility, we showcase successful applications of our method in both low-frequency and high-frequency sensing scenarios. The significance of this quantum sensing technique extends to the detection of complex signals and the control of intricate quantum environments. By enhancing detection accuracy and enabling precise manipulation of quantum systems, our method holds considerable promise for a variety of practical applications.

Quantitative regulation of electron-phonon coupling.

Electron-phonon (e-p) coupling plays a crucial role in various physical phenomena, and regulation of e-p coupling is vital for the exploration and design of high-performance materials. However, the current research on this topic lacks accurate quantification, hindering further understanding of the underlying physical processes and its applications. In this work, we demonstrate quantitative regulation of e-p coupling, by pressure engineering andin-situspectroscopy. We successfully observe both a distinct vibrational mode and a strong Stokes shift in layered CrBr3, which are clear signatures of e-p coupling. This allows us to achieve precise quantification of the Huang-Rhys factorSat the actual sample temperature, thus accurately determining the e-p coupling strength. We further reveal that pressure efficiently regulates the e-p coupling in CrBr3, evidenced by a remarkable 40% increase inSvalue. Our results offer an approach for quantifying and modulating e-p coupling, which can be leveraged for exploring and designing functional materials with targeted e-p coupling strengths.

Carboxymethyl cellulose/quaternized chitosan hydrogel loaded with polydopamine nanoparticles promotes spinal cord injury recovery by anti-ferroptosis and M1/M2 polarization modulation.

Spinal cord injury (SCI) represents a catastrophic neurological condition resulting in long-term loss of motor, autonomic, and sensory functions. Recently, ferroptosis, an iron-regulated form of cell death distinct from apoptosis, has emerged as a potential therapeutic target for SCI. In this study, we developed an injectable hydrogel composed of carboxymethyl cellulose (CMC), and quaternized chitosan (QCS), loaded with modified polydopamine nanoparticles (PDA NPs), referred to as CQP hydrogel. This hydrogel effectively scavenged reactive oxygen species (ROS), prevented the accumulation of Fe2+ and lipid peroxidation associated with ferroptosis, and restored mitochondrial functions in primary neuronal cells. When administered to animal models (rats) with SCI, the CQP hydrogels improved motor function by regulating iron homeostasis, inhibiting ferroptosis, and mitigating oxidative stress injury. Both in vitro and in vivo studies corroborated the capacity of CQP hydrogels to promote the shift from M1 to M2 polarization of microglia/macrophages. These findings suggest that CQP hydrogels, functioning as a localized iron-chelating system, have potential as biomaterials to enhance recovery from SCI by targeting ferroptosis and modulating anti-inflammatory macrophages activity.

Development of a 1-step multiplex PCR assay for the detection of S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis associated with poultry production.

Salmonellosis in poultry is detrimental to the advancement of the breeding industry and poses hazards to human health. Approximately 2,600 Salmonella varieties exist, among which S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis are prevalent serotypes in the poultry industry in recent years. They can also infect humans by contaminating poultry eggs and meat. Therefore, identifying these serotypes is crucial for successful preventive and control interventions. The White-Kauffmann-Le Minor scheme is time-consuming and requires expensive reagents. Whole-genome sequencing (WGS) and other molecular biology techniques require skilled technical staff. In comparison, the polymerase chain reaction (PCR) is more accurate, rapid, and inexpensive, thus proving suitable for widespread application in the poultry industry. Here, we selected 4 specific primers: lygD, mdh, ipaJ, and SIN_02055, which correspond to detecting S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, respectively. They were integrated into a 1-step multiplex PCR method. We optimized the PCR method by utilizing specificity test results to determine the optimal annealing temperature (57°C). The PCR method exhibited excellent sensitivity for genomic DNA and bacterial cultures. We used the developed method to determine 157 clinical Salmonella isolates from various stages of the poultry production chain. The results aligned with serotype data generated via WGS analysis, demonstrating the method's excellent accuracy. In conclusion, this study developed a 1-step multiplex PCR method that simultaneously identifies S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, allowing routine mass detection in the grass-root poultry industry.

A rapid, ultrasensitive, and highly specific method for detecting fowl adenovirus serotype 4 based on the LAMP-CRISPR/Cas12a system.

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium hepatitis syndrome in chickens, which causes severe economic impact to the poultry industry. A simple, swift and reliable detection is crucial for timely identification of FAdV-4 infection, promoting effective viral prevention and control measures. Herein, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12a (Cas12a) system detection platform based on loop-mediated isothermal amplification (LAMP) was studied. The CRISPR RNA (crRNA) and LAMP primers were designed and screened based on the highly conserved region of the FAdV-4 hexon gene. The parameters were then optimized individually to achieve the ideal reaction performance. The platform could lead visual detection of FAdV-4 to achieve as low as 1 copy in less than 40 min without the need for specialized instrumentation or complex equipment. Moreover, it was greatly specific, and did not cross-react with other common avian viruses. Following the validation of 30 clinical samples of suspected FAdV-4 infection, the results LAMP-CRISPR/Cas12a method generated showed fully concordance with which of the gold standard quantitative real-time PCR. To summarize, this study presented a novel, swift, expedient and inexpensive detection platform for FAdV-4, which is beneficial to viral inchoate diagnosis and point-of-care testing.

Establishment and Application of Novel Hypoxia-driven Dual-reporter Model to Investigate Hypoxic Impact on Radiation Sensitivity in Human Nasopharyngeal Carcinoma Xenografts.

Background: Tumor hypoxia has been frequently detected in nasopharyngeal carcinoma (NPC) and is intently associated with therapeutic resistance. The aim of the study is to establish a clonogenically stable hypoxia-inducible dual reporter model and apply it to investigate the effect of tumor hypoxia on DNA double strand break (DSB) and synergistic effect of irradiation in combination with chemotherapy or targeted therapy. Methods: The plasmid vector consisting of hypoxia response elements to regulate HSV1-TK and GFP genes, was constructed and stably transfected into human NPC cells. The expected clone was identified and validated by in vivo and in vitro assay. DSB repair was measured by γH2AX foci formation. Tumor growth delay assay and spatial biodistribution of various biomarkers was designed to investigate the anti-tumor effect. Results: The system has the propensity of high expression of reporter genes under hypoxia and low to no expression under normoxia. Intratumoral biodistributions of GFP and classic hypoxic biomarkers were identical in poor-perfused region. Upon equilibration with 10% O2, the xenografts showed higher expression of hypoxic biomarkers. Cisplatin radiosensitized SUNE-1/HRE cells under hypoxia by suppressing DSB repair while the addition of PI3K/mTOR inhibitor further enhanced the anti-tumoral therapeutic efficacy. Combination of IR, DDP and NVP-BEZ235 exhibited most effective anti-tumor response in vivo. These observations underline the importance of dual reporter model for imaging tumor hypoxia in therapeutic study. Conclusions: Our preclinical model enables the investigation of heterogeneous tumor hypoxic regions in xenograft tissues and explores the treatment efficacy of combinations of various therapeutic approaches to overcome hypoxia.

Multifunctional Lithium Phytate/Carbon Nanotube Double-Layer-Modified Separators for High-Performance Lithium-Sulfur Batteries.

Li dendrite and the shuttle effect are the two primary hindrances to the commercial application of lithium-sulfur batteries (LSBs). Here, a multifunctional separator has been fabricated via successively coating carbon nanotubes (CNTs) and lithium phytate (LP) onto a commercial polypropylene (PP) separator to improve the performance of LSBs. The LP coating layer with abundant electronegative phosphate group as permselective ion sieve not only reduces the polysulfide shuttle but also facilitates uniform Li+ flux through the PP separator. And the highly conductive CNTs on the second layer act as a second collector to accelerate the reversible conversion of sulfide species. The synergistic effect of LP and CNTs further increases the electrolyte wettability and reaction kinetics of cells with a modified separator and suppresses the shuttle effect and growth of Li dendrite. Consequently, the LSBs present much enhanced rate performance and cyclic performance. It is expected that this study may generate an executable tactic for interface engineering of separator to accelerate the industrial application process of LSBs.

Amino-modified nanoplastics at predicted environmental concentrations cause transgenerational toxicity through activating germline EGF signal in Caenorhabditis elegans.

In the real environment, some chemical functional groups are unavoidably combined on the nanoplastic surface. Reportedly, amino-modified polystyrene nanoparticles (PS-A NPs) exposure in parents can induce severe transgenerational toxicity, but the underlying molecular mechanisms remain largely unclear. Using Caenorhabditis elegans as the animal model, this study was performed to investigate the role of germline epidermal growth factor (EGF) signal on modulating PS-A NPs' transgenerational toxicity. As a result, 1-10 µg/L PS-A NPs exposure transgenerationally enhanced germline EGF ligand/LIN-3 and NSH-1 levels. Germline RNAi of lin-3 and nsh-1 was resistant against PS-A NPs' transgenerational toxicity, implying the involvement of EGF ligand activation in inducing PS-A NPs' transgenerational toxicity. Furthermore, LIN-3 overexpression transgenerationally enhanced EGF receptor/LET-23 expression in the progeny, and let-23 RNAi in F1-generation notably suppressed PS-A NPs' transgenerational toxicity in the exposed worms overexpressing germline LIN-3 at P0 generation. Finally, LET-23 functioned in neurons and intestine for regulating PS-A NPs' transgenerational toxicity. LET-23 acted at the upstream DAF-16/FOXO within the intestine in response to PS-A NPs' transgenerational toxicity. In neurons, LET-23 functioned at the upstream of DAF-7/DBL-1, ligands of TGF-ß signals, to mediate PS-A NPs' transgenerational toxicity. Briefly, this work revealed the exposure risk of PS-A NPs' transgenerational toxicity, which was regulated through activating germline EGF signal in organisms.

Distribution and spread of tigecycline resistance gene tet(X4) in Escherichia coli from different sources.

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with tet(X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene tet(X) in E. coli isolates from various origins in Yangzhou, China, to provide insights into tet(X) dissemination in this region. In 2022, we tested the presence of tet(X) in 618 E. coli isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of tet(X)-positive E. coli isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on tet(X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried tet(X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The tet(X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These tet(X4)-carrying plasmids exhibited high similarity to other tet(X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of tet(X4) associated with ISCR2, as observed in the first identified tet(X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of tet(X) in E. coli strains was observed in this study, the horizontal transfer of tet(X4) among E. coli isolates mediated by pandemic plasmids and the mobile element ISCR2 raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.