Resveratrol protects cardiomyocytes against ischemia/reperfusion-induced ferroptosis via inhibition of the VDAC1/GPX4 pathway.

The present study aimed to explore how resveratrol (Res) confers myocardial protection by attenuating ferroptosis. In vivo and in vitro myocardial ischemia/reperfusion injury (MIRI) models were established, with or without Res pretreatment. The results showed that Res pretreatment effectively attenuated MIRI, as evidenced by increased cell viability, reduced lactate dehydrogenase activity, decreased infarct size, and maintained cardiac function. Moreover, Res pretreatment inhibited MIRI-induced ferroptosis, as shown by improved mitochondrial integrity, increased glutathione level, decreased prostaglandin-endoperoxide synthase 2 level, inhibited iron overload, and abnormal lipid peroxidation. Of note, Res pretreatment decreased or increased voltage-dependent anion channel 1/glutathione peroxidase 4 (VDAC1/GPX4) expression, which was increased or decreased via anoxia/reoxygenation (A/R) treatment, respectively. However, the overexpression of VDAC1 via pAd/VDAC1 and knockdown of GPX4 through Si-GPX4 reversed the protective effect of Res in A/R-induced H9c2 cells, whereas the inhibition of GPX4 with RSL3 abolished the protective effect of Res on mice treated with ischemia/reperfusion.Interestingly, knockdown of VDAC1 by Si-VDAC1 promoted the protective effect of Res on A/R-induced H9c2 cells and the regulation of GPX4. Finally, the direct interaction between VDAC1 and GPX4 was determined using co-immunoprecipitation. In conclusion, Res pretreatment could protect the myocardium against MIRI-induced ferroptosis via the VDAC1/GPX4 signaling pathway.

Aggregation induced emission dynamic chiral europium(III) complexes with excellent circularly polarized luminescence and smart sensors.

The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S-Eu-R-1, R = Et/Me; R/S-Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5D0 → 7F1) and 2429 M-1cm-1 of R-Eu-Et-1, achieving a rare double improvement. R-Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

Exploring the molecular biology of ischemic cardiomyopathy based on ferroptosis­related genes.

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome.

Determination and human health risk assessment of TFWT, OBT and carbon-14 in seafood around Qinshan Nuclear Power Plant.

This work aims to evaluate the effects of the operation of Qinshan nuclear Power Plant (QNPP) on tritium (3H) and carbon-14 (14C) levels in seafood and assess the health risks caused by seafood consumption. Five kinds of seafood, including marine fish, prawn, razor clam, crabs, and seaweed, were collected from QNPP and the sea around Hangzhou Bay. The activity concentrations of tissue free water tritium (TFWT), organically bound tritium (OBT) and 14C were determined, respectively, and the annual intake and annual effective dose (AED) were calculated. The results showed that the TFWT, OBT, and 14C activity concentrations of the seafood in the surrounding area of QNPP ranged from 2.00 to 74.75 Bq/L, <1.04 to 19.68 Bq/L and 0.09 to 0.17 Bq/g·C, respectively. The TFWT, OBT, and 14C activity concentrations of the seafood in Hangzhou Bay ranged from 1.36 to 10.55 Bq/L, 1.08 to 6.78 Bq/L and 0.07 to 0.13 Bq/g·C, respectively. The differences were not statistically significant. The total AED from 3H and 14C due to the seafood consumption for the residents in the surrounding of QNPP and Hangzhou Bay were 1.96 × 10-4 and 1.61 × 10-4 mSv/year, respectively. The results showed that the operation of QNPP had no obvious effect on 3H and 14C accumulation in seafood, and the dose burden of population was low.

Different anion (NO3- and OAc-)-controlled construction of dysprosium clusters with different shapes.

The complex hydrolysis process and strong uncertainty of self-assembly rules have led to the precise synthesis of lanthanide clusters still being in the "blind-box" stage and simplifying the self-assembly process and developing reliable regulation strategies have attracted widespread attention. Herein, different anions are used to induce the construction of a series of dysprosium clusters with different shapes and connections. When the selected anion is NO3-, it blocks the coordination of metal sites around the cluster through the terminal group coordination mode, thereby controlling the growth of the cluster. When NO3- was changed to OAc-, OAc- adopted a bridging mode to induce modular units to build dysprosium clusters through an annular growth mechanism. Specifically, we selected 2-amino-6-methoxybenzoic acid, 2-hydroxybenzaldehyde, and Dy(NO3)3·6H2O to react under solvothermal conditions to obtain a pentanuclear dysprosium cluster (1). The five Dy(III) ions in 1 are distributed in upper and lower planes and are formed by the tight connection of nitrogen and oxygen atoms, and µ3-OH- bridges on the ligand. Next, octa-nuclear dysprosium cluster (2) were obtained by only regulating ligand substituents. The eight Dy(III) ions in 2 are tightly connected through ligand oxygen atoms, µ2-OH-, and µ3-OH- bridges, forming an elliptical {Dy/O} cluster core. Furthermore, only by changing NO3- to OAc-, a wheel-shaped tetradeca-nuclear dysprosium cluster (3) was obtained. Cluster 3 is composed of OAc- bridged multiple template Dy3L3 units and pulling of these template units connected by an annular growth mechanism forms a wheel-shaped cluster. The angle of the coordination site on NO3- is ∠ONO = 115°, which leads to the further extension of the metal sites on the periphery of clusters 1 and 2 through the terminal group coordination mode, thereby regulating the structural connection of the clusters. However, the angle of the coordination site on OAc- is ∠OCO = 128°, and a slightly increased angle leads to the formation of a ring-shaped cluster 3 by connecting the template units through bridging. This is a rare example of the controllable construction of lanthanide clusters with different shapes induced by the regulation of different anions, which provides a new method for the precise construction of lanthanide clusters with special shapes.

New insights into changes in phosphorus profile at sediment-water interface by microplastics: Role of benthic bioturbation.

Microplastics (MPs) have attracted increasing attention due to their ubiquitous occurrence in freshwater sediments and the detrimental effects on benthic invertebrates. However, a clear understanding of their downstream impacts on ecosystem services is still lacking. This study examines the effects of bio-based polylactic acid (PLA), fuel-based polyethylene terephthalate (PET), and biofilm-covered PET (BPET) MPs on the bioturbator chironomid larvae (Tanypus chinensis), and the influence on phosphorus (P) profiles in microcosms. The changes in biochemical responses and metabolic pathways indicated that MPs disrupted energy synthesis by causing intestinal blockage and oxidative stress in T. chinensis, leading to energy depletion and impaired bioturbation activity. The impairment further resulted in enhanced sedimentary P immobilization. For larval treatments, the internal-P loadings were respectively 11.4%, 8.6%, and 9.0% higher in the PLA, PET, and BPET groups compared to the non-MP control. Furthermore, the influence of bioturbation on P profiles was MP-type dependent. Both BPET and PLA treatments displayed more obvious impacts on P profiles compared to PET due to the changes in MP bioavailability or sediment microenvironment. This study connects individual physiological responses to broader ecosystem services, showing that MPs alter P biogeochemical processes by disrupting the bioturbation activities of chironomid larvae.

CSINet: A Cross-Scale Interaction Network for Lightweight Image Super-Resolution.

In recent years, advancements in deep Convolutional Neural Networks (CNNs) have brought about a paradigm shift in the realm of image super-resolution (SR). While augmenting the depth and breadth of CNNs can indeed enhance network performance, it often comes at the expense of heightened computational demands and greater memory usage, which can restrict practical deployment. To mitigate this challenge, we have incorporated a technique called factorized convolution and introduced the efficient Cross-Scale Interaction Block (CSIB). CSIB employs a dual-branch structure, with one branch extracting local features and the other capturing global features. Interaction operations take place in the middle of this dual-branch structure, facilitating the integration of cross-scale contextual information. To further refine the aggregated contextual information, we designed an Efficient Large Kernel Attention (ELKA) using large convolutional kernels and a gating mechanism. By stacking CSIBs, we have created a lightweight cross-scale interaction network for image super-resolution named "CSINet". This innovative approach significantly reduces computational costs while maintaining performance, providing an efficient solution for practical applications. The experimental results convincingly demonstrate that our CSINet surpasses the majority of the state-of-the-art lightweight super-resolution techniques used on widely recognized benchmark datasets. Moreover, our smaller model, CSINet-S, shows an excellent performance record on lightweight super-resolution benchmarks with extremely low parameters and Multi-Adds (e.g., 33.82 dB@Set14 × 2 with only 248 K parameters).

Prognosis value of circulating tumor cell PD­L1 and baseline characteristics in patients with NSCLC treated with immune checkpoint inhibitors plus platinum­containing drugs.

Immune checkpoint inhibitors (ICIs) combined with platinum-containing chemotherapy are recommended as the standard first-line treatment for non-small cell lung cancer (NSCLC). However, specific prognostic markers for this combination therapy are yet to be identified. Evaluation of circulating tumor cells (CTCs) and cell surface programmed death-ligand 1 (PD-L1) exhibits potential in predicting the efficacy of the aforementioned combination therapy. Thus, the present study aimed to evaluate the prognostic value of CTC PD-L1 testing and other clinical characteristics in patients with NSCLC treated with combination therapy as first-line treatment. In total, 40 patients with advanced NSCLC were included in the present study, and all patients underwent CTC PD-L1 testing at initial diagnosis to determine the association between CTC PD-L1 and tissue PD-L1. The prognostic value of CTC PD-L1 and the baseline characteristics of 26 patients with NSCLC were analyzed, and the prognostic values of changes in CTC PD-L1 and baseline characteristics during 6 months of treatment were further explored. Results of the present study demonstrated that there was no association between CTC PD-L1 and tissue PD-L1 levels. After 6 months of combination therapy, tumor shrinkage, CYFA19 levels and treatment maintenance were associated with progression-free survival (PFS) of patients. Notably, CTC PD-L1 and tissue PD-L1 levels, TNM stage, nutritional score, inflammation score and other blood indicators were not associated with PFS. In conclusion, the evaluation of CTCs and CTC PD-L1 suggested that undetectable CTCs at 6 months of NSCLC treatment are associated with a good prognosis. In addition, negative CTC PD-L1 expression may change to positive CTC PD-L1 expression in line with disease progression, and this may be indicative of poor prognosis.

Escherichia coli and HPV16 coinfection may contribute to the development of cervical cancer.

Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli's coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Revealing the drivers and genesis of NO3-N pollution classification in shallow groundwater of the Shaying River Basin by explainable machine learning and pathway analysis method.

Nitrate (NO3-N), as one of the ubiquitous contaminants in groundwater worldwide, has posed a serious threat to public health and the ecological environment. Despite extensive research on its genesis, little is known about the differences in the genesis of NO3-N pollution across different concentrations. Herein, a study of NO3-N pollution concentration classification was conducted using the Shaying River Basin as a typical area, followed by examining the genesis differences across different pollution classifications. Results demonstrated that three classifications (0-9.98 mg/L, 10.14-27.44 mg/L, and 28.34-136.30 mg/L) were effectively identified for NO3-N pollution using Jenks natural breaks method. Random forest exhibited superior performance in describing NO3-N pollution and was thereby affirmed as the optimal explanatory method. With this method coupling SEMs, the genesis of different NO3-N pollution classifications was proven to be significantly different. Specifically, strongly reducing conditions represented by Mn2+, Eh, and NO2-N played a dominant role in causing residual NO3-N at low levels. Manure and sewage (represented by Cl-) leaching into groundwater through precipitation is mainly responsible for NO3-N in the 10-30 mg/L classification, with a cumulative contribution rate exceeding 80 %. NO3-N concentrations >30 mg/L are primarily caused by the anthropogenic loads stemming from manure, sewage, and agricultural fertilization (represented by Cl- and K+) infiltrating under precipitation in vulnerable hydrogeological conditions. Pathway analysis based on standardized effect and significance further confirmed the rationality and reliability of the above results. The findings will provide more accurate information for policymakers in groundwater resource management to implement effective strategies to mitigate NO3-N pollution.

Multi-omics reveals the switch role of abnormal methylation in the regulation of decidual macrophages function in recurrent spontaneous abortion.

RSA, recurrent spontaneous abortion, often causes serious physical damage and psychological pressure in reproductive women with unclarified pathogenesis. Abnormal function of decidual cells and aberrant DNA methylation have been reported to cause RSA, but their association remains unclear. Here, we integrated transcriptome, DNA methylome, and scRNA-seq to clarify the regulatory relationship between DNA methylation and decidual cells in RSA. We found that DNA methylation mainly influenced the function of decidual macrophages (DMs), of which four hub genes, HLA-A, HLA-F, SQSTM1/P62, and Interferon regulatory factor 7 (IRF7), related to 22 hypomethylated CpG sites, regulated 16 hub pathways to participate in RSA pathogenesis. In particular, using transcription factor analysis, it is suggested that the upregulation of IRF7 transcription was associated with enhanced recruitment of the transcription factor STAT1 by the hypomethylated promoter region of IRF7. As the current research on DNA methylation of macrophages in the uterine microenvironment of RSA is still blank, our systematic picture of abnormal DNA methylation in regulating DM function provides new insights into the role of DNA methylation in RSA occurrence, which may aid in further prevention and treatment of RSA.

[Spatiotemporal Occurrence of Organophosphate Esters in the Surface Water and Sediment of Taihu Lake and Relevant Risk Assessment].

Aiming to explore the spatiotemporal occurrence of organophosphate esters (OPEs) in the aquatic environment of Taihu Lake and to assess the relevant ecological risk, monomeric and oligomeric OPEs in the surface water and sediment of Taihu Lake were determined using solid phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry. The target monomeric OPEs included chlorinated OPEs, alkyl OPEs, and aryl OPEs. There was no significant difference in the spatial distribution of OPEs in water and sediment between the pollutant-impacted and less-impacted zones. The average concentrations of OPEs in summer and winter were, respectively, 752.7 and 498.5 ng·L-1 in water and 124.0 and 54.5 ng·g-1 in sediment, indicating an obvious seasonal difference, especially for the monomeric OPEs. The OPEs levels in both the water and sediment were ranked in the order of chlorinated OPEs > alkyl OPEs > aryl OPEs≈oligomeric OPEs. The pseudo-partitioning coefficients (Kd) of OPEs between the sediment and surface water of Taihu Lake were much higher in summer (0.05-4.17 L·g-1) compared to those in winter (0.02-3.47 L·g-1) and were significantly positively correlated with the lg Kow values of OPEs. Based on the median concentrations of OPEs in the water of Taihu Lake, the ecological risk of OPEs was assessed by risk quotient (RQ) values, which indicated a medium risk at an RQ level of 0.34 during winter and 0.35 during summer. The assessment results showed that the risk ranking of OPEs was consistent with that of their concentrations, and the monomeric OPEs posed a higher ecological risk in summer compared to that in winter. Although the ecological risk of oligomeric OPEs in this study was not serious and was lower than that of monomeric OPEs, it is an urgent requirement to conduct ecotoxicology studies on oligomeric OPEs in the future since available data is highly limited at present.

Coordination recognition of differential template units of lanthanide chiral chain.

Coordination-driven self-assembly processes often produce remarkable structures. In particular, self-assembly processes mediated by chiral template units have provided research ideas for analyzing the formation of chiral macromolecules in living organisms. In this study, by regulating the proportion of reaction raw materials in the "one-pot" synthesis of lanthanide complexes, we constructed chiral template units with different coordination orientations. As a result, lanthanide chiral chains connected to different structures were obtained through the self-assembly process of coordination recognition. In particular, driven by coordination, chiral template units with codirectional coordination points (called cis configuration) coordinate solely with cis template units during the self-assembly process to obtain a one-dimensional (1D) chain R-1/S-1 with an "S"-shaped distribution. Moreover, chiral template units with reversed coordination sites (called trans configuration) and twisted chiral template units are connected solely to templates with the same configuration to form a 1D chain R-2/S-2 with an axial helix. A circular dichroism spectrum shows that R-1/S-1 and R-2/S-2 are two pairs of enantiomers. The controllable construction of these two differential 1D chains is of great significance for studying coordination recognition at the molecular level. To the best of our knowledge, this is the first study to construct a 1D lanthanide chain through the self-assembly process of coordination recognition. The assembly process of nucleotides to form a hierarchical structure is simulated. This work provides a vivid example of the controllable synthesis of lanthanide complexes with precise structures and offers a new perspective on the formation process of chiral macromolecules that simulates natural processes.

Revealing discrepancies and drivers in the impact of lomefloxacin on groundwater denitrification throughout microbial community growth and succession.

The coexistence of antibiotics and nitrates has raised great concern about antibiotic's impact on denitrification. However, conflicting results in these studies are very puzzling, possibly due to differences in microbial succession stages. This study investigated the effects of the high-priority urgent antibiotic, lomefloxacin (LOM), on groundwater denitrification throughout microbial growth and succession. The results demonstrated that LOM's impact on denitrification varied significantly across three successional stages, with the most pronounced effects exhibited in the initial stage (53.8% promotion at 100 ng/L-LOM, 84.6% inhibition at 100 µg/L-LOM), followed by the decline stage (13.3-18.2% inhibition), while no effect in the stable stage. Hence, a distinct pattern encompassing susceptibility, insusceptibility, and sub-susceptibility in LOM's impact on denitrification was discovered. Microbial metabolism and environment variation drove the pattern, with bacterial numbers and antibiotic resistance as primary influencers (22.5% and 15.3%, p < 0.01), followed by carbon metabolism and microbial community (5.0% and 3.68%, p < 0.01). The structural equation model confirmed results reliability. Bacterial numbers and resistance influenced susceptibility by regulating compensation and bacteriostasis, while carbon metabolism and microbial community impacted energy, electron transfer, and gene composition. These findings provide valuable insights into the complex interplay between antibiotics and denitrification patterns in groundwater.

Synthesis of dimpled polymer-silica nanocomposite particles by interfacial swelling-based seeded polymerization.

Dimpled polymer-silica nanocomposite particles have the combined advantages of dimpled particles and polymer-silica nanocomposite particles. This study presents a novel approach to prepare these particles by interfacial swelling-based seeded polymerization. Polystyrene-silica (PS-SiO2) nanocomposite particles are first prepared by emulsion polymerization of styrene in the presence of glycerol-functionalized silica sols and then dimpled polymer-SiO2 particles are fabricated by interfacial swelling of butyl acrylate (BA)/toluene and subsequent seeded polymerization of BA with the PS-SiO2 particles as seeds. The effects of different parameters, such as the amount of surfactant used in the PS-SiO2/H2O dispersion, BA/toluene mass ratio, PS-SiO2/H2O mass ratio and stirring rate, on the formation of the dimpled particles are investigated. Optimization of the seeded polymerization conditions allows a relatively high percentage of dimpled particles to be achieved.

Persistent ciprofloxacin exposure induced the transformation of Klebsiella pneumoniae small colony variant into mucous phenotype.

Introduction: Small colony variant (SCV) is a bacterial phenotype closely related to persistent and recurrent infections. SCVs are mutations that occur within bacterial populations, resulting in a change in bacterial morphology and the formation of small colonies. This morphological change may enhance bacterial resistance to antibiotics and contribute to persistent and recurrent infections. Methods: We isolated Klebsiella pneumoniae (KPN) and its SCV from a child with recurrent respiratory tract infections. KPN and SCV were treated with subinhibitory concentrations of antibiotics. growth curves, serum resistance experiments, macrophage phagocytosis experiments and whole genome sequencing were used to characterize KPN and SCV. Results: After treating KPN and SCV with subinhibitory concentrations of antibiotics, we found that ciprofloxacin induced the SCV transition to the mucoid phenotype. We found that the growth of mucoid Klebsiella pneumoniae was significantly slower than maternal strain and SCV though growth curves. Serum resistance experiments showed that mucoid strains had significantly higher serum resistance compared to maternal strain and SCV. Macrophage phagocytosis experiments revealed that SCV had significantly higher intracellular survival rates compared to maternal strain and mucoid strains. Differential gene analysis of three strains revealed that the mucoid strain contained DNA polymerase V subunit UmuC gene on the plasmid, while the SCV strain had an additional IcmK family IV secretion protein on its plasmid. Discussion: Our study showed the SCV of KPN changed to a mucoid colony when exposed to subinhibitory concentrations of ciprofloxacin. The higher resistance of serum of mucoid colonies was possibly related to the UmuC gene, while the increased intracellular survival of SCV may be related to the IcmK family type IV secretion proteins.

Aggregation-Induced Emission via the Restriction of the Intramolecular Vibration Mechanism of Pinacol Lanthanide Complexes.

Pinacol lanthanide complexes PyraLn (Ln = Dy and Tb) with the restriction of intramolecular vibration were obtained for the first time via an in situ solvothermal coordination-catalyzed tandem reaction using cheap and simple starting materials, thereby avoiding complex, time-consuming, and expensive conventional organic synthesis strategies. A high-resolution electrospray ionization mass spectrometry (HRESI-MS) analysis confirmed the stability of PyraLn in an organic solution. The formation process of PyraLn was monitored in detail using time-dependent HRESI-MS, which allowed for proposing a mechanism for the formation of pinacol complexes via in situ tandem reactions under one-pot coordination-catalyzed conditions. The PyraLn complexes constructed using a pinacol ligand with a butterfly configuration exhibited distinct aggregation-induced emission (AIE) behavior, with the αAIE value as high as 60.42 according to the AIE titration curve. In addition, the PyraLn complexes in the aggregated state exhibit a rapid photoresponse to various 3d metal ions with low detection limits. These findings provide fast, facile, and high-yield access to dynamic, smart lanthanide complex emissions with bright emission and facilitate the rational construction of molecular machines for artificial intelligence.

Investigation of critical factors influencing the underestimation of hearing loss predicted by the ISO 1999 predicting model.

OBJECTIVE: To analyze factors influencing the underestimation of noise-induced permanent threshold shift (NIPTS) among manufacturing workers, providing baseline data for revising noise exposure standard. DESIGN: A cross-sectional study was designed with 2702 noise-exposed workers from 35 enterprises from 10 industries. Personal noise exposure level(LAeq,8h) and noise kurtosis level were determined by a noise dosimeter. Questionnaires and hearing loss tests were performed for each subject. The predicted NIPTS was calculated using the ISO 1999:2013 model for each participant, and the actual measured NIPTS was corrected for age and sex. The factors influencing the underestimation of NIPTS were investigated. RESULTS: The predicted NIPTS at each test frequency (0.5, 1, 2, 3, 4, or 6kHz) and mean NIPTS at 2, 3, 4, and 6kHz (NIPTS2346) using the ISO 1999:2013 model were significantly lower than their corresponding measured NIPTS, respectively (P < 0.001). The ISO model significantly underestimated the NIPTS2346 by 12.36 dB HL. The multiple linear regression analysis showed that noise exposure level, exposure duration, age, and kurtosis could affect the degree of underestimation of NIPTS2346. The generalized additive model (GAM) with (penalized) spline components showed nonlinear relationships between critical factors (age, exposure duration, noise level, and kurtosis) and the underestimated NIPTS2346.The underestimated NIPTS2346 decreased with an increase in exposure duration (especially over ten years). There was no apparent trend in the underestimated NIPTS2346 with age. The underestimated NIPTS2346 decreased with the increased noise level [especially > 90 dB(A)]. The underestimated NIPTS2346 increased with an increase in noise kurtosis after adjusting for the noise exposure level and exposure duration and ultimately exhibiting a linear regression relationship. CONCLUSIONS: The ISO 1999 predicting model significantly underestimated the noise-induced hearing loss among manufacturing workers. The degree of underestimation became more significant at the noise exposure condition of fewer than ten years, less than 90 dB(A), and higher kurtosis levels. It is necessary to apply kurtosis to adjust the underestimation of hearing loss and consider the applying condition of noise energy metrics when using the ISO predicting model.

Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1.

Tanshinone IIA (TSN) extracted from danshen (Salvia miltiorrhiza) could protect cardiomyocytes against myocardial ischemia/reperfusion injury (IRI), however the underlying molecular mechanisms of action remain unclear. The aim of the present study was to identify the protective effects of TSN and its mechanisms of action through in vitro studies. An anoxia/reoxygenation (A/R) injury model was established using H9c2 cells to simulate myocardial IRI in vitro. Before A/R, H9c2 cardiomyoblasts were pretreated with 8 µM TSN or 10 µM ferrostatin­1 (Fer­1) or erastin. The cell counting kit 8 (CCK­8) and lactate dehydrogenase (LDH) assay kit were used to detect the cell viability and cytotoxicity. The levels of total iron, glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), ferrous iron, caspase­3 activity, and reactive oxygen species (ROS) were assessed using commercial kit. The levels of mitochondrial membrane potential (MMP), lipid ROS, cell apoptosis, and mitochondrial permeability transition pore (mPTP) opening were detected by flow cytometry. Transmission electron microscopy (TEM) was used to observed the mitochondrial damage. Protein levels were detected by western blot analysis. The interaction between TSN and voltage­dependent anion channel 1 (VDAC1) was evaluated by molecular docking simulation. The results showed that pretreatment with TSN and Fer­1 significantly decreased cell viability, glutathione peroxidase 4 (GPX4) protein and GSH expression and GSH/GSSG ratio and inhibited upregulation of LDH activity, prostaglandin endoperoxide synthase 2 and VDAC1 protein expression, ROS levels, mitochondrial injury and GSSG induced by A/R. TSN also effectively inhibited the damaging effects of erastin treatment. Additionally, TSN increased MMP and Bcl­2/Bax ratio, while decreasing levels of apoptotic cells, activating Caspase­3 and closing the mPTP. These effects were blocked by VDAC1 overexpression and the results of molecular docking simulation studies revealed a direct interaction between TSN and VDAC1. In conclusion, TSN pretreatment effectively attenuated H9c2 cardiomyocyte damage in an A/R injury model and VDAC1­mediated ferroptosis and apoptosis served a vital role in the protective effects of TSN.