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Microplastics have become ubiquitous in the global marine environment, posing substantial influences on marine organism health, food web function and marine ecosystem structure. Protozoan grazers are known for their ability to improve the biochemical constituents of poor-quality algae for subsequent use by higher trophic levels. However, the effects of microplastics on the trophic upgrading of protozoan grazers remain unknown. To address this knowledge gap, the ciliate Euplotes vannus and the heterotrophic dinoflagellate Oxyrrhis marina were exposed to microplastic particles (5 μm) for four days with various concentrations (1-20 mg/L). Both O. marina and E. vannus ingested microplastics. At the exposure level of 20 mg/L, the ingestion rate, growth rate, biovolume, and carbon biomass of E. vannus were significantly decreased by 28.18 %, 32.01 %, 30.46 %, and 82.27 %, respectively, while such effects were not observed for O. marina. The contents of highly unsaturated fatty acids in O. marina and E. vannus on a mixed diet of microplastic particles and green algae significantly reduced by 8.66 % and 41.49 % relative to feeding only on green algae, respectively. Besides, we also observed an increase in the composition of C18:3 (ω-3) and C20:3 (ω-3) concurrence with a significant decrease in C16:0 and C18:0 in E. vannus after 96 h exposure at 20 mg/L. These results indicate that microplastics can weaken trophic upgrading of the nutritional quality by protozoan grazers, which may consequently alter the function of food webs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to electronegativity (EN) differences, changing from C 3 N 4 to P 4 C 3 is not as trivial as simply replacing nitrogen by phosphorus in the C 3 N 4 structure. Hence, the nonexistent P 4 C 3 phase is nominally the higher-homologue analogue of the well-known C 3 N 4 , but its structure and properties are practically unknown for fundamental reasons. Here we predict, by means of an extensive structure search, three energetically favorable yet metastable P 4 C 3 phases adopting space groups P 1̅, Cm , and Cmmm , followed by designing their synthetic routes. Different from the planar structural motifs of C 3 N 4 , P 4 C 3 is likely to adopt various "puckered" (as regards the P atoms) forms, mainly related to the EN difference between nitrogen and phosphorus, the difference in atomic size, and also less favorable sp orbital mixing for phosphorus related to primogenic repulsion; hence, the P substructures are characterized by single and fractional P-P bonds with rectangular/linear motifs or those resembling simple-cubic P, including multicenter bonding as a function of the large electron count. As regards the carbon substructures, infinite polyacetylene-like motifs, carbon dimers, and infinite chains of cyclopentadienyl-like and polyphenyl-like units are predicted, with C-C bond orders larger than one. Band structure analyses indicate the metallic character of these three phases. The P 1̅ polymorph exhibits a Dirac cone, whereas the Cmmm phase, being composed of metallic "phosphorene" units and infinite polyphenyl units, might show potential in applications, e.g., battery electrodes. Moreover, the monolayer of the P 1̅ polymorph should be easy to exfoliate and exhibit a large anisotropy with regard to mechanical and electronic properties. The synthesis of P 4 C 3 defining a new class of IV 3 V 4 compounds should be attempted due to its predicted structural and physicochemical properties.

Due to the serious detrimental impact on human health, antibiotic pollution particularly tetracyclines residues has become a serious problem. Herein, a multiple response fluorescent probe consisted of dual-emission carbon dots and Eu 3+ (D-CDs@Eu 3+ ) is designed for the determination and discrimination of tetracyclines (TCs). Specifically, the carboxyl and amidogen group of dual-emission carbon dots (D-CDs) can coordinate with Eu 3+ to form the D-CDs@Eu 3+ . Upon adding TCs, the fluorescence intensities of D-CDs at 405 nm and 495 nm are quenched due to inner filter effect (IFE) and the localization of fluorescence resonance energy transfer (L-FRET) between the D-CDs@Eu 3+ and TC. Simultaneously, the D-CDs@Eu 3+ may chelate with TCs to enhance the occurrence of antenna effect, while the characteristic peaks of Eu 3+ at 590 nm and 615 nm are enhanced. On these bases, the TCs detection is achieved with low detection limits from 46.7 to 72.0 nM. Additionally, through the distinct efficiencies of L-FRET, the discrimination of TCs is achieved. Moreover, a novel centrifugated lateral flow assay strips (CLFASs) device is developed by integrating the D-CDs@Eu 3+ , lateral flow assay strips and smartphone using RGB variations for TCs detection, achieving remarkable recoveries (98.6-103.7 %) in real samples. Therefore, this CLFASs device provides a reliable approach for the TCs detection, demonstrating potential applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of precise diagnosis and the discovery of individualized drugs go together to provide effective therapy against inflammatory bowel disease (IBD). The exploitation of the unique imaging advantages of chemiluminescent probes represents a pivotal strategy for achieving this goal. Nevertheless, the dual-locked strategy, which is believed to enhance precision, is rarely employed in the design of chemiluminescent probes. A novel dual-locked chemiluminescent probe, BPan-CL , was designed based on IBD candidate biomarkers chymotrypsin (CHT) and vanin-1. BPan-CL exhibited specific reactivity and chemiluminescence response when subjected to simultaneous stimulation of CHT and vanin-1, with a signal-to-noise ratio superior to that of the fluorescent probe with the same dual-locked mode. In both live cell and IBD mice imaging, BPan-CL demonstrated superior sensitivity compared to its single-locked counterpart, Pan-CL . In contrast to Pan-CL , BPan-CL was able to more accurately identify IBD and healthy mice by in vivo imaging and allowed for early prediction of IBD using a noninvasive fecal test. BPan-CL has identified CHT and vanin-1 as valuable combinatorial biomarkers for accurate and early IBD diagnosis. This strategy has significant potential for use in biomedical imaging and future individualized therapies.

Competing Interests: The authors have no financial or conflicts of interest to disclose.

Bisphenols (BPs) are widely distributed in daily life as typical endocrine disruptors. In this study, we examined the distribution of bisphenol A (BPA) and BPA alternatives in liver (n = 149) and bile (n = 102) tissues from the patients with liver cancer, and calculated the hepatobiliary transport efficiency of BPs (T B-L ). Seven BPs were detected in both liver (median: 0.859 ng/g; range: 0.0200-26.7 ng/g) and bile (median: 0.307 ng/mL; range: 0.0200-26.7 ng/mL), and BPA was the predominant in both liver (mean: 1.89 ng/g) and bile (mean: 1.65 ng/mL). The T B-L of BPs was reported for the first time and found to be negatively correlated with the molecular weight and Log K ow of BPs. Furthermore, BPA and ∑BPs in liver showed a significant negative correlation with age, and a significant difference was found in BPs in liver and bile in hepatocellular carcinoma patients with different genders (p < 0.05). For liver function indicators, levels of BPs showed significant positive correlation with γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT), especially BPBP levels in bile. This suggests that BPs may have some correlation with hepatocellular carcinoma. This is the first report on distribution characteristics of BPs in the liver and bile of hepatocellular carcinoma patients, and is the first study to report the hepatobiliary transport efficiency of BPs. The results should contribute to the understanding of BPs accumulation in the liver and bile and further relationship with hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

An omnidirectional stretchable strain sensor with high resolution is a critical component for motion detection and human-machine interaction. It is the current dominant solution to integrate several consistent units into the omnidirectional sensor based on a certain geometric structure. However, the excessive similarity in orientation characteristics among sensing units restricts orientation recognition due to their closely matched strain sensitivity. In this study, based on strain partition modulation (SPM), a sensitivity anisotropic amplification strategy is proposed for resistive strain sensors. The stress distribution of a sensitive conductive network is modulated by structural parameters of the customized periodic hole array introduced underneath the elastomer substrate. Meanwhile, the strain isolation structures are designed on both sides of the sensing unit for stress interference immune. The optimized sensors exhibit excellent sensitivity (19 for 0-80%; 109 for 80%-140%; 368 for 140%-200%), with nearly a 7-fold improvement in the 140%-200% interval compared to bare elastomer sensors. More importantly, a sensing array composed of multiple units with different hole configurations can highlight orientation characteristics with amplitude difference between channels reaching up to 29 times. For the 48-class strain-orientation decoupling task, the recognition rate of the sensitivity-differentiated layout sensor with the lightweight deep learning network is as high as 96.01%, superior to that of 85.7% for the sensitivity-consistent layout. Furthermore, the application of the sensor to the fitness field demonstrates an accurate recognition of the wrist flexion direction (98.4%) and spinal bending angle (83.4%). Looking forward, this methodology provides unique prospects for broader applications such as tactile sensors, soft robotics, and health monitoring technologies.

In urban to peri-urban watersheds such as those surrounding San Francisco Bay, stormwater runoff is a major pathway by which contaminants enter aquatic ecosystems. We evaluated the occurrence of 154 organic contaminants via liquid chromatography coupled to tandem mass spectrometry, including organophosphate esters (OPEs), bisphenols, per- and polyfluoroalkyl substances (PFASs), and a suite of novel urban stormwater tracers (SWCECs; i.e. , vehicle-derived chemicals, pesticides, pharmaceuticals/personal care products, benzothiazoles/benzotriazoles). Time-averaged composite sampling focused on storms in highly developed watersheds over four wet seasons, with complementary sampling in less-urban reference watersheds, near-shore estuarine sites, and the open Bay. Of the targeted contaminants, 68 (21 SWCECs, 29 OPEs, 3 bisphenols, 15 PFASs) were detected in ≥10 of 26 urban stormwater samples. Median concentrations exceeded 500 ng L -1 for 1,3-diphenylguanidine, hexa(methoxymethyl)melamine, and caffeine, and exceeded 300 ng L -1 for 2-hydroxy-benzothiazole, 5-methyl-1 H -benzotriazole, pentachlorophenol, and tris(2-butoxyethyl) phosphate. Median individual PFAS concentrations were <10 ng L -1 , with highest concentrations for PFHxA (180 ng L -1 ), PFOA (110 ng L -1 ), and PFOS (81 ng L -1 ). In six of eight urban stormwater samples analyzed for 6PPD-quinone (a tire rubber-derived transformation product), concentrations exceeded coho salmon acute toxicity thresholds, suggesting (sub)lethal impacts for sensitive species. Observed concentrations were generally significantly higher in highly developed watersheds relative to reference watersheds, but not statistically different in near-shore estuarine sites, suggesting substantial transient exposure potential at stormwater outfalls or creek outflows. Results emphasized the role of stormwater in contaminant transport, the importance of vehicles/roadways as contaminant sources, and the value of monitoring broad multi-analyte contaminant suites to enable comprehensive source and toxicity evaluations.

Background: Several recent studies have confirmed that intratumoural microorganisms can affect the occurrence and development of hepatocellular carcinoma (HCC); however, their role in tumor progression remains unclear. Hence, there is a need for further research on the role of intratumoural microorganisms in HCC., Aim: To investigate the changes in intratumoural microorganisms in HCC and the effect of Propionibacterium on HCC progression., Methods: HCC and normal liver tissue specimens were subjected to fluorescence in situ hybridization (FISH). After performing 16S rRNA sequencing on HCC and peritumoral tissues to analyze the differences between the two groups. Propionibacterium was cocultured with HCC cells in vitro . Changes in cell proliferation and migration capacity were evaluated. The expression of NF-κB pathway related proteins in tumor cells was compared. The orthotopic liver implantation model and the subcutaneous xenograft model were constructed. liver tissues and subcutaneous tumors were collected 2 weeks later., Results: FISH demonstrated the presence of microorganisms in HCC and normal liver tissues. 16S rRNA sequencing revealed an abundance of Lysobacter , Lachnospiraceae , Pseudomonas , and Lactobacillus in HCC tissues. The distribution and abundance of Propionibacterium showed differences between HCC and peritumoral tissues ( P < 0.05). In vitro studies demonstrated that Propionibacterium and its metabolite propionic acid (PA) inhibited the proliferation and migration of HCC cells ( P < 0.05). The expression of the proteins in NF-κB signaling pathway also decreased in HCC cells ( P < 0.05)., Conclusion: Microorganisms in HCC and normal liver tissues displayed significant disparities. The PA-producing bacterium Propionibacterium in HCC exerts an effect on the NF-κB pathway, thereby affecting the biological behavior of HCC., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Meteorin-like (Metrnl) is a novel adipokine which is highly expressed in adipose tissue and has a beneficial effect on glucose and lipid metabolism. High density lipoprotein cholesterol (HDL-C) is well recognized to be inversely associated with cardiovascular events. However, the relationship between serum Metrnl levels and HDL-C in the type 2 diabetes mellitus (T2DM) remains unclear. Therefore, the present study aimed to evaluate the association of serum Metrnl with HDL-C levels in T2DM., Materials and Methods: Eighty participants with T2DM were included in this cross-sectional study. They were divided into two groups according to HDL-C levels: Group1 (lower HDL-C group): HDL-C < 1.04 mmol/L; Group2 (higher HDL-C group): HDL-C ≥ 1.04 mmol/L. Serum Metrnl levels were measured by enzyme-linked immunosorbent assay (ELISA)., Results: As compared with lower HDL-C levels groups, serum Metrnl levels were significantly higher in the group with higher HDL-C. Binary logistic regression analysis showed serum Metrnl levels were positively associated with HDL-C group after adjustment with sex, age, body mass index (BMI), mean arterial pressure (MAP), fasting blood glucose (FPG), triglyceride (TG). Furthermore, serum Metrnl levels were inversely correlated with insulin resistance index (HOMA-IR). HDL-C levels were lowest in the group with the lowest Metrnl levels group and remained positively associated with Metrnl after adjustment for sex, age, BMI, TG, and HOMA-IR by using multivariate logistic regression analysis., Conclusion: Serum Metrnl levels were positively associated with HDL-C levels in patients with T2DM.This suggests that increasing serum Metrnl levels maybe a candidate for improving lipid metabolism and preventing cardiovascular events in T2DM., Registry and the Registration No of the Study/trial: The study was registered in the Chinese clinical trial registry (ChiCTR- 2100047148)., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhou et al.)

High harmonic generation (HHG) have received significant attention for the exploration of material properties and ultrafast dynamics. However, the lack of consideration for couplings between HHG and other quasiparticles, such as phonons, has been impeding the understanding of many-body interactions in HHG. Here, we reveal the many-body electron-phonon mechanism in the quasiparticle-coupled strong-field dynamics by investigating the nonadiabatic (NA) coherent-phonon-coupled HHG. Coherent phonons are revealed to effectively affect HHG via the adiabatic band modulation induced by phonon deformation effects and the NA and nonequilibrium distribution of photocarriers in multiple valleys. The adiabatic and NA mechanisms leave their fingerprint via influencing the phonon period and phase delay in the oscillation of HHG intensity, both of which are experimentally measurable. Investigation of these quantities enables the direct probing of the electron-phonon interaction in materials.

The activation of an inert C( sp 3 )-H bond in selective oxidation of hydrocarbons under mild conditions is a critical and challenging process. Herein, we report a stable chlorine-coordinated metal-organic framework (MOF) photocatalyst, MIL-101(Fe), for efficient visible-light-driven photocatalytic selective oxidation of toluene to benzaldehyde in air under ambient conditions. Encouragingly, a benzaldehyde formation yield of 3.11 mmol·g -1 ·h -1 with a selectivity of 92.1% is achieved in 5 h, which is superior to most of the reported works. Based on the experimental results and characterizations, the high catalytic performance is mainly due to the promoted rate-limiting step of C( sp 3 )-H bond activation by a chlorine radical (Cl·) from the coordinated -Cl in the MIL-101(Fe) structure. In addition, the present photocatalyst possesses good substrate tolerance for photocatalytic selective oxidation of various toluene derivatives under optimized conditions.

Epimedium is widely used in traditional Chinese medicine and contains rich bioactive compounds. These compounds often have a methyl group at their 4'-OH position catalyzed by methyltransferases. Therefore, studying methyltransferases in Epimedium plants is of great significance. In this study, a flavonol methyltransferase, EpOMT4, was isolated from Epimedium pseudowushanense B.L. Guo. The recombinant enzyme regiospecifically transferred a methyl group to the 4'-OH position of 8-prenylkaempferol forming icaritin. The study demonstrates that enzymatic methylation of flavonoids in Epimedium plants holds significant potential and could provide a promising alternative method for the biosynthetic production of bioactive methylated prenylflavonoids.

Antibiotic resistome has emerged as a global threat to public health. However, gestational antibiotic resistome and potential link with adverse pregnancy outcomes remains poorly understood. Our study reports for the first time an association between gut antibiotic resistome during early pregnancy and the risk of gestational diabetes mellitus (GDM) based on a prospective nested case-control cohort including 120 cases and 120 matched controls. A total of 214 antibiotic resistance gene (ARG) subtypes belonging to 17 ARG types were identified in > 10 % fecal samples collected during each trimester. The data revealed dynamic profiles of gut antibiotic resistome through pregnancy, and significant positive associations between selected features (i.e., ARG abundances and a GDM-ARG score which is a new feature characterizing the association between ARGs and GDM) of gut antibiotic resistome during early pregnancy and GDM risk as well as selected endogenous metabolites. The findings demonstrate ubiquitous presence of ARGs in pregnant women and suggest it could constitute an important risk factor for the development of GDM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G 4 S 1 ) 3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 μg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 μg and 20 μg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Optical coherence tomography angiography (OCTA) plays a crucial role in quantifying and analyzing retinal vascular diseases. However, the limited field of view (FOV) inherent in most commercial OCTA imaging systems poses a significant challenge for clinicians, restricting the possibility to analyze larger retinal regions of high resolution. Automatic stitching of OCTA scans in adjacent regions may provide a promising solution to extend the region of interest. However, commonly-used stitching algorithms face difficulties in achieving effective alignment due to noise, artifacts and dense vasculature present in OCTA images. To address these challenges, we propose a novel retinal OCTA image stitching network, named MR 2 -Net, which integrates multi-scale representation learning and dynamic location guidance. In the first stage, an image registration network with a progressive multi-resolution feature fusion is proposed to derive deep semantic information effectively. Additionally, we introduce a dynamic guidance strategy to locate the foveal avascular zone (FAZ) and constrain registration errors in overlapping vascular regions. In the second stage, an image fusion network based on multiple mask constraints and adjacent image aggregation (AIA) strategies is developed to further eliminate the artifacts in the overlapping areas of stitched images, thereby achieving precise vessel alignment. To validate the effectiveness of our method, we conduct a series of experiments on two delicately constructed datasets, i.e., OPTOVUE-OCTA and SVision-OCTA. Experimental results demonstrate that our method outperforms other image stitching methods and effectively generates high-quality wide-field OCTA images, achieving a structural similarity index (SSIM) score of 0.8264 and 0.8014 on the two datasets, respectively.

Studying the interaction between pesticide contamination in the plant system and the dissolved organic matter (DOM) composition is important to understand the impact of pesticides and plants on the ecological function of DOM. The present study investigated the effects of DOM on the bioaccumulation and biotransformation of carbamates in plants, carbamate exposure on DOM composition, and plant root secretion on the interaction between DOM and carbamates. The concentrations of carbamates and their metabolites in living cabbage plants were continuously tracked through an in vivo analytical method. The presence of DOM was found to reduce the highest bioconcentrations and shorten the time it took to reach the highest bioaccumulated amounts of isoprocarb and carbofuran in plants, while it showed no significant effect on the uptake behavior of carbaryl. DOM profiling results indicated that carbamate exposure substantially decreased the number and molecular diversity of DOM. Notably, plant root secretion alleviated carbamate-induced DOM molecular alterations by inducing a higher turnover rate of DOM compared to that in the uncontaminated group, highlighting the role of plants in mitigating the effects of exogenous pesticide exposure on DOM composition and maintaining DOM molecular homeostasis.

Objective: To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms., Methods: The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-β 1 (TGF-β 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-β 1, TGF-β 1+10% DMS, TGF-β 1+10% DMS+miR-29b-2-5p inhibitor, TGF-β 1+10% DMS+inhibitor negative control, TGF-β 1+10% DMS+miR-29b-2-5p mimic and TGF-β 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA., Results: The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01)., Conclusions: Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Glycoside hydrolases (GHs), enzymes that break down glycosidic bonds in carbohydrates and between carbohydrates and non-carbohydrates, are prevalent in plants, animals, microorganisms, and other organisms. The tomato is a significant crop that contains the GH17 gene family. However, its role in tomatoes has yet to be fully investigated. In this study, we identified 43 GH17 genes from the tomato genome, distributed unevenly across 12 chromosomes. We further analyzed their gene structure, phylogenetic relationships, promoter elements, and expression patterns. The promoter element analysis indicated their potential roles in response to biotic and abiotic stresses as well as phytohormone effects on growth and development. The expression studies across different tomato tissues revealed that 10 genes were specifically expressed in floral organs, with SlA6 prominently expressed early during bud formation. By using CRISPR/Cas9 gene-editing technology, SlA6 knockout plants were generated. Phenotypic characterization showed that pollen viability, pollen tube germination, fruit weight, and seed number were significantly reduced in the Sla6 mutant, but the soluble solids content (TSS) was significantly higher in the Sla6 mutant, suggesting that SlA6 affects pollen development and fruit quality.

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objectives: This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors., Methods: The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test., Results: The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival ( P  = 0.004) and overall survival ( P  < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival ( P  = 0.0021) and overall survival ( P  < 0.0001)., Conclusions: The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear., Methods: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed., Results: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively., Conclusions: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L., Trial Registration: ClinicalTrials.gov ID: NCT02633358., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine differences in failure rate and hearing outcomes of a completely encircling heat-activated crimping prosthesis (SMart 360°) compared to partially encircling prosthesis (SMart)., Study Design: Retrospective chart review., Setting: Private neurotology tertiary referral center., Patients: Patients who underwent stapedotomies performed by the senior authors from 2008 to 2019 using the SMart prosthesis and SMart 360° prothesis., Interventions: Stapedotomy operations with placement of a SMart or SMart 360° prosthesis., Main Outcome Measures: Incidence of early failure requiring revision surgery. Differences in preoperative air-bone gap (ABG) compared to postoperative ABG at 3 months, 1 year, and 2 years after surgery., Results: A total of 228 stapedotomies were performed (SMart n = 48 and SMart 360° n = 180). Mean preoperative ABG for SMart and SMart 360° were 26.15 and 29 dB, respectively. The mean difference in ABG for the SMart at 3 months, 1 year, and 2 years were 17, 18, and 11 dB, respectively. The mean difference in ABG for the SMart 360° at 3 months, 1 year, and 2 years were 20, 20, and 19 dB. ABG differences at 3 months (p = 0.10) and 1 year (p = 0.36) were not statistically different. The failure rate for the SMart prosthesis was 12.5% and for the SMart 360° 2.2% (p = 0.002)., Conclusions: There were no statistically significant differences in ABG changes for SMart compared to SMart 360°. The Smart 360 corrects the problem with early failure seen with the Smart prosthesis., Professional Practice Gap and Educational Need: Determination of most efficacious stapes prosthesis., Learning Objective: Which stapes prosthesis produces better hearing results with fewer failures., Desired Result: To disseminate information necessary to choose the best stapes prosthesis for patients., Level of Evidence: Level III., Indicate Irb or Iacuc: 2022-029-agh., Competing Interests: Conflicts of interest: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Leprosy, also known as Hansen disease, is an airborne spread disease caused by Mycobacterium leprae ( M. leprae ) which commonly presents with skin lesions, peripheral neuropathy, and ocular involvement. This report describes a patient who presented with epiphora secondary to chronic nasolacrimal duct obstruction four years after completing antimicrobial treatment for tuberculoid leprosy. At the time of endoscopic dacryocystorhinostomy (DCR), the lacrimal sac demonstrated chronic dacryocystitis with granulomatous inflammation and a Fite positive staining bacterial rod-like structure. Pathological examination of the surgical specimen demonstrated numerous non-necrotizing granulomas in a perivascular and neural distribution, compatible with sequelae of previously treated M. leprae infection. The patient has remained symptom free six months after surgery.

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive tumor with extremely poor prognosis due to the low resection rate, high recurrence rate and drug resistance. Uridine-cytidine kinase 2 (UCK2) is proved to promote progression and drug resistance of various carcinomas by regulating pyrimidine metabolism. However, the role of UCK2 in progression and drug resistance of iCCA was largely unclear. Gene expression matrices were obtained from public database and were verified by qRT-PCR using tumor sample from Sun Yat-sen University Cancer Center. Knockdown and overexpression of UCK2 were used to evaluate the effects of UCK2 on carcinogenesis and cisplatin response in iCCA. CCK8-kit assays and plate clone formation assays were performed to detect the effect of UCK2 on proliferative activity of tumor cells. Western blotting was performed to investigate protein level of UCK2 and the relevant biomarkers of PI3K/AKT/mTOR/autophagic axis. Cell migration and invasion were assessed by using wound-healing and transwell assays. UCK2 expression was detected elevated in iCCA tissues compared with adjacent normal tissues. Biologically, overexpression of UCK2 can promote proliferation of iCCA cells, and desensitizes iCCA to cisplatin in both in vivo and in vitro models. Mechanistically, UCK2 promote iCCA progression and cisplatin resistance through inhibition of autophagy by activating the PI3K/AKT/mTOR signaling pathway. Clinically, higher UCK2 expression in iCCA tumor was associated with aggressive tumor features, poorer survival and lower sensitivity of chemotherapy. UCK2 promotes iCCA progression and desensitizes cisplatin treatment by regulating PI3K/AKT/mTOR/autophagic axis. UCK2 exhibited potential as a biomarker in predicting prognosis and drug sensitivity of iCCA patients., (© 2024. The Author(s).)

Urinary analysis of exogenous and endogenous molecules constitutes an efficient, noninvasive approach to evaluate human health status. However, the exposome characterization of urinary molecules remains extremely challenging with current techniques. Herein, we develop an ExpoNano strategy based on hyper-cross-linked polymers (HCPs) to achieve ultrahigh-throughput measurement of exo/endogenous molecules in urine. The strategy includes a simple trapping-detrapping procedure (15 min) with HCPs in enzymatically treated urine, followed by mass spectrometer determination. Molecules that can be determined by ExpoNano have a wide range of molecular weight (75-837 Da) and Log K ow (octanol-water partition coefficient; -9.86 to 10.56). The HCPs can be repeatedly used five times without decreasing the trapping efficiency. Application of ExpoNano in a biomonitoring study revealed a total of 63 environmental chemicals detected in >50% of the urine pools collected from Chinese adults living in 13 cities, with a median concentration of 0.026-47 ng/mL, while nontargeted analysis detected an additional 243 exogenous molecules. Targeted and nontargeted analysis also detected 926 endogenous molecules in pooled urine. Collectively, the ExpoNano strategy demonstrates unique advantages over traditional urine analysis approaches, including a wide range of analytes, satisfactory trapping efficiency, high simplicity and reusability, and extremely reduced time demand and financial cost.

Aims: To assess whether mechanical circulatory support (MCS), including intra-aortic balloon pump (IABP) or veno-arterial extracorporeal membrane oxygenation (ECMO), can help improve neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA)., Methods: This is a retrospective observational cohort study performed in China Medical University Hospital, Taichung, Taiwan. Adult patients with OHCA admitted between January 2015 and June 2023. Quantitative score of vasoactive-inotropic agents and qualitative interventions of MCS, including IABP and ECMO after OHCA. Multivariate regression evaluated the efficacy of each MCS approach in patients stratified by the vasoactive-inotropic score (VIS)., Results: A total of 334 patients were included and analyzed, 122 (36.5%) had favorable neurological outcomes and 215 (64.4%) survived ≥90 days. These patients were stratified by VIS: 0-25, 26-100, 101-250, and >250. In patients with a VIS > 100, ECMO with or without IABP ensured favorable neurological outcomes and survival after OHCA compared to non-MCS interventions ( p  < 0.001). For patients with a VIS ≤ 100, IABP alone was beneficial, with no significant outcome difference from non-MCS interventions ( p  > 0.05)., Conclusions: ECMO with or without IABP therapy may improve post-OHCA neurological outcomes and survival in patients with an expected VIS-24 h > 100 (e.g., epinephrine dose reaches 3 mg during CPR)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation., Methods: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1β, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA., Results: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1β in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16., Conclusions: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH., Methods: We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages., Results: We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation., Conclusion: We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K-AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH., (© 2024. The Author(s).)

Background: Citrus huanglongbing (HLB) is a devastating disease caused by Candidatus Liberibacter asiaticus (CLas) that affects the citrus industry. In nature, CLas relies primarily on Diaphorina citri Kuwayama as its vector for dissemination. After D. citri ingests CLas-infected citrus, the pathogen infiltrates the insect's body, where it thrives, reproduces, and exerts regulatory control over the growth and metabolism of D. citri. Previous studies have shown that CLas alters the composition of proteins in the saliva of D. citri, but the functions of these proteins remain largely unknown., Results: In this study, we detected two proteins (DcitSGP1 and DcitSGP3) with high expression levels in CLas-infected D. citri. Quantitative PCR and Western blotting analysis showed that the two proteins were highly expressed in the salivary glands and delivered into the host plant during feeding. Silencing the two genes significantly decreased the survival rate for D. citri, reduced phloem nutrition sucking and promoted jasmonic acid (JA) defenses in citrus. By contrast, after overexpressing the two genes in citrus, the expression levels of JA pathway-associated genes decreased., Conclusion: Our results suggest that CLas can indirectly suppress the defenses of citrus and support feeding by D. citri via increasing the levels of effectors in the insect's saliva. This discovery facilitates further research into the interaction between insect vectors and pathogens. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Continuous emission monitoring system is commonly employed to monitor NOx emissions in municipal solid waste incineration (MSWI) processes. However, it still encounters the challenges of regular maintenance and measurement lag. These issues significantly impact the accurate and stable control of NOx emissions. Therefore, developing a soft NOx emission sensor to complement hardware monitoring becomes imperative. Considering data noise, dynamic nonlinearity, time series characteristics and volatility in the MSWI process, this article introduces a soft sensor model for NOx emission prediction utilizing the complete ensemble empirical mode decomposition adaptive noise (CEEMDAN)-wavelet threshold (WT) method and bidirectional long short-term memory (Bi-LSTM). Firstly, the original data signal is decomposed into a group of intrinsic mode functions (IMFs) using the CEEMDAN. Subsequently, the WT processes the high-frequency IMFs that are noise-dominant. Then, all IMFs are reconstructed to obtain the denoized signal. Finally, the Bi-LSTM model is employed to predict NOx emissions. Compared to conventional modelling approaches, the model proposed in this article demonstrates the best predictive performance. The mean absolute percentage error, root-mean-squared error and average absolute error on the test set of the proposed model are 3.75%, 5.34 mg m -3 and 4.34 mg m -3 , respectively. The proposed model provides a new method to soft sensing NOx emissions. It holds significant practical value for precise and stable monitoring of NOx emissions in MSWI processes and provides a reference for research on modelling key process parameters., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR)., Methods: Genetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results., Results: There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58-2.33; p < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; p < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; p < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications., Conclusion: Our findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Shi, Zhao, Abuduani, Chen, Chen, Wang and Li.)

The induction of viable but nonculturable (VBNC) bacteria with cellular integrity and low metabolic activity by chemical disinfection causes a significant underestimation of potential microbiological risks in drinking water. Herein, a physical Co 3 O 4 nanowire-assisted electroporation (NW-EP) was developed to induce cell damage via the locally enhanced electric field over nanowire tips, potentially achieving effective inhibition of VBNC cells as compared with chemical chlorination (Cl 2 ). NW-EP enabled over 5-log removal of culturable cell for various G+/G- bacteria under voltage of 1.0 V and hydraulic retention time of 180 s, and with ∼3-6 times lower energy consumption than Cl 2 . NW-EP also achieved much higher removals (∼84.6 % and 89.5 %) of viable Bacillus cereus (G+) and Acinetobacter schindleri (G-) via generating unrecoverable pores on cell wall and reversible/irreversible pores on cell membrane than Cl 2 (∼28.6 % and 41.1 %) with insignificant cell damage. The residual VBNC bacteria with cell wall damage and membrane pore resealing exhibited gradual inactivation by osmotic stress, leading to ∼99.8 % cell inactivation after 24 h storage (∼59.4 % for Cl 2 ). Characterizations of cell membrane integrity and cell morphology revealed that osmotic stress promoted cell membrane damage for the gradual inactivation of VBNC cells during storage. The excellent adaptability of NW-EP for controlling VBNC cells in DI, tap and lake waters suggested its promising application potentials for drinking water, such as design of an external device on household taps., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Limited proteolysis, CaCl 2 and carboxymethyl cellulose (CMC) have individually demonstrated ability to increase the gel strength of laboratory-extracted plant proteins. However, the syneresis effects of their combination on the gelling capacity of commercial plant protein remains unclear. This was investigated by measuring the rheological property, microstructure and protein-protein interactions of gels formed from Alcalase hydrolyzed or intact pea proteins in the presence of 0.1 % CMC and 0-25 mM CaCl 2 . Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed the molecular weight of pea protein in the mixture were < 15 kDa after hydrolysis. The hydrolysates showed higher intrinsic fluorescence intensity and lower surface hydrophobicity than the intact proteins. Rheology showed that the storage modulus (G') of hydrolyzed pea protein (PPH)-based gels sightly decreased compared to those of native proteins. 5-15 mM CaCl 2 increased the G' for both PP and PPH-based gels and decreased the strain in the creep-recovery test. Scanning electron microscopy (SEM) showed the presence of smaller protein aggregates in the PPH-based gels compared to PP gels and the gel network became denser, and more compact and heterogenous in the presence of 15 and 25 mM CaCl 2 . The gel dissociation assay revealed that hydrophobic interactions and hydrogen bonds were the dominant forces to maintain the gel structure. In vitro digestion showed that the soluble protein content in PPH-based gels was 10 ∼ 30 % higher compared to those of the PP counterpart. CaCl 2 addition reduced protein digestibility with a concentration dependent behavior. The results obtained show contrasting effects of limited proteolysis and CaCl 2 on the gelling capacity and digestibility of commercial pea proteins. These findings offer practical guidelines for developing pea protein-based food products with a balanced texture and protein nutrition through formulation and enzymatic pre-treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 μg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17β, cyp19a1) and attenuated the TCS-decreased estradiol (E 2 ) in females. Conversely, testosterone levels were suppressed, and E 2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3β, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The exposure levels of phthalates in humans have dropped dramatically. Little is known about the individual and joint effects of phthalates exposure at low levels on the risk of early miscarriage., Objective: To examine the association between exposure to phthalates individually or as a mixture and early miscarriage., Methods: A case-control study was conducted in Shanghai, China during 2019-2020. A total of 291 women seeking medical services due to miscarriage (cases) and 308 women planning to terminate an unintended pregnancy (controls) within 12 gestational weeks were recruited. Urinary concentrations of eight phthalate metabolites were determined by ultra-performance liquid chromatography. We included 534 women in the main analysis who had available data on both phthalates exposure and complete information on potential confounders. We used logistic regression and Bayesian kernel machine regression (BKMR) to examine the associations of concentrations of phthalates with miscarriage., Results: Among the phthalate metabolites, mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) had the highest concentration (8.10 ng/mL), followed by mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, 2.68 ng/mL) and monobutyl phthalate (MBP, 2.24 ng/mL). Higher concentrations of MBP, mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP and the molar sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHPm) were associated with an increased risk of miscarriage exhibiting a dose-response relationship. The most evident association of miscarriage was found with ∑DEHPm, with adjusted odds ratio (95% confidence interval) of 1.94 (1.14, 3.31) for the second quartile, 2.83 (1.67, 4.79) for the third quartile and 4.28 (2.49, 7.37) for the fourth quartile compared to the first quartile. Consistently, the phthalate mixture was positively associated with the risk of miscarriage and DEHP was the predominant contributor to the joint effect in BKMR model., Impact: Phthalates are a family of synthetic chemicals mainly used as plasticizers, solvents and additives in a large variety of industrial and consumer products, including food packing materials, toys, gloves, medical devices and personal care products. Although exposure levels of phthalates of pregnant women have declined sharply over the past few decades, phthalates exposure was still associated with an increased risk of early miscarriage. Our findings suggest that future researchers and policy makers might need to take low-dose effects of phthalates into account regarding the reproductive toxicity of phthalates exposure in humans., Significance: Our findings contribute to the awareness of the reproductive toxic potential of phthalates at low levels in humans and support the ongoing efforts to further reduce exposure to phthalates., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 μg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 μg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM)., Aim: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels., Methods: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy., Results: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c ( P < 0.05), whereas HOMA-β was negatively correlated with the HbA1c level ( P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control., Conclusion: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Soil heavy metal contamination has become a global environmental issue, which threaten soil quality, food security and human health. Symphytum officinale L. have exhibited high tolerance and restoration capacity to heavy metals (HMs) stress. However, little is known about the mechanisms of HMs in S. officinale. In this study, transcriptomic and physiological changes of S. officinale response to different HMs (Pb, Cd and Zn) were analyzed and investigated the key genes and pathways involved in HMs uptake patterns. The results showed that phenotypic effects are not significant, and antioxidant enzyme activities were all upregulated. Transcriptome analysis indicated that 1247 differential genes were up-regulated, and 1963 differential genes were down-regulated under Cd stress, while 3752 differential genes were up-regulated, and 7197 differential genes were down-regulated under Pb stress; and 527 differential genes were up-regulated; and 722 differential genes were down-regulated under Zn stress. Based on their expression, we preliminarily speculate that different HMs resistance of S. officinale may be regulated by the differential expression of key genes. These results provide a theoretical basis for determining the exact expression of genes in plants under different heavy metal stress, the processes involved molecular pathways, and how they can be efficiently utilized to improve plant tolerance to toxic metals and improve phytoremediation efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg -1 ·d -1 , ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1β. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Photocatalysis is one of the most promising pathways to relieve the environmental contamination caused by the rapid development of modern technology. In this work, we demonstrate a green manufacturing process for the 3D/3D rod-shaped bamboo charcoal/Bi 2 WO 6 photocatalyst (210BC-BWO) by controlled carbonization temperature. A series of morphology characterization and properties investigations (XRD, SEM, UV-vis DRS, transient photocurrent response, N 2 absorption-desorption isotherms) indicate a 210BC-BWO photocatalyst with higher charge separation efficiency, larger surface area, and better adsorption capacity. The excellent photocatalytic performance was evaluated by degrading rhodamine B (RhB) (98.5%), tetracycline hydrochloride (TC-HCl) (77.1%), and H 2 evolution (2833 μmol·g -1 ·h -1 ) coupled with furfuryl alcohol oxidation (3097 μmol·g -1 ·h -1 ) under visible light irradiation. In addition, the possible mechanisms for degradation of organic pollutants, H 2 evolution, and furfuryl alcohol oxidation were schematically investigated, which make it possible to exert photocatalysis by increasing the active radical. This study shows that the combination of bamboo charcoal and bismuth tungstate can be a powerful photocatalyst that rationally combines H 2 evolution coupled with furfuryl alcohol oxidation and degradation of pollutants.

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 μg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma., Competing Interests: Da-Fu Chen is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)

A ratiometric fluorescence sensor has been established based on dual-excitation carbon dots (D-CDs) for the detection of flavonoids (morin is chosen as the typical detecting model for flavonoids). D-CDs were prepared using microwave radiation with o-phenylenediamine and melamine and exhibit controllable dual-excitation behavior through the regulation of their concentration. Remarkably, the short-wavelength excitation of D-CDs can be quenched by morin owing to the inner filter effect, while the long-wavelength excitation remains insensitive, serving as the reference signal. This contributes to the successful design of an excitation-based ratiometric sensor. Based on the distinct and differentiated variation of excitation intensity, morin can be determined from 0.156 to 110 µM with a low detection limit of 0.156 µM. In addition, an intelligent and visually lateral flow sensing device is developed for the determination  of morin content in real samples with satisfying recoveries, which indicates the potential application for human health monitoring., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A smarter city should be a safer city. Nighttime safety in metropolitan areas has long been a global concern, particularly for large cities with diverse demographics and intricate urban forms, whose citizens are often threatened by higher street-level crime rates. However, due to the lack of night-time urban appearance data, prior studies based on street view imagery (SVI) rarely addressed the perceived night-time safety issue, which can generate important implications for crime prevention. This study hypothesizes that night-time SVI can be effectively generated from widely existing daytime SVIs using generative AI (GenAI). To test the hypothesis, this study first collects pairwise day-and-night SVIs across four cities diverged in urban landscapes to construct a comprehensive day-and-night SVI dataset. It then trains and validates a day-to-night (D2N) model with fine-tuned brightness adjustment, effectively transforming daytime SVIs to nighttime ones for distinct urban forms tailored for urban scene perception studies. Our findings indicate that: (1) the performance of D2N transformation varies significantly by urban-scape variations related to urban density; (2) the proportion of building and sky views are important determinants of transformation accuracy; (3) within prevailed models, CycleGAN maintains the consistency of D2N scene conversion, but requires abundant data. Pix2Pix achieves considerable accuracy when pairwise day-and-night-night SVIs are available and are sensitive to data quality. StableDiffusion yields high-quality images with expensive training costs. Therefore, CycleGAN is most effective in balancing the accuracy, data requirement, and cost. This study contributes to urban scene studies by constructing a first-of-its-kind D2N dataset consisting of pairwise day-and-night SVIs across various urban forms. The D2N generator will provide a cornerstone for future urban studies that heavily utilize SVIs to audit urban environments.

Photon blockade (PB) is one of the effective methods to generate single-photon sources. In general, both the PB effect with the significant sub-Poissonian statistics and a large mean photon number are desired to guarantee the brightness and the purity of single-photon sources. Here, we propose to obtain the PB effect at the cavity dark-state polariton (DSP) using a cavity Λ-type electromagnetically induced transparency (EIT) system with and without the two-photon dissipation (TPD). In the Raman resonance case, the PB effect at the DSP could by realized by using the TPD process in the weak or intermediate coupling regime, which accompanies with near unity transmission, i.e., very high photon occupation. In the slightly detuned Raman resonance case, the excited state is induced into the components of the DSP, and the atomic dissipation path is added into the two-photon excitation paths. Thus, the PB effect at the DSP can be obtained due to the quantum destructive interference (QDI) in the strong coupling regime, which can be further enhanced using the TPD process. Due to the slight detuning, the PB effect still remains high photon occupation and has highly tunability. This work provides an alternative way to manipulate the photon statistics by the PB effect and has potential applications in generating single-photon sources with high brightness and purity.