Memory-less scattering imaging with ultrafast convolutional optical neural networks.

The optical memory effect in complex scattering media including turbid tissue and speckle layers has been a critical foundation for macroscopic and microscopic imaging methods. However, image reconstruction from strong scattering media without the optical memory effect has not been achieved. Here, we demonstrate image reconstruction through scattering layers where no optical memory effect exists, by developing a multistage convolutional optical neural network (ONN) integrated with multiple parallel kernels operating at the speed of light. Training this Fourier optics-based, parallel, one-step convolutional ONN with the strong scattering process for direct feature extraction, we achieve memory-less image reconstruction with a field of view enlarged by a factor up to 271. This device is dynamically reconfigurable for ultrafast multitask image reconstruction with a computational power of 1.57 peta-operations per second (POPS). Our achievement establishes an ultrafast and high energy-efficient optical machine learning platform for graphic processing.

A non-linear partial least squares based on monotonic inner relation.

A novel regression model, monotonic inner relation-based non-linear partial least squares (MIR-PLS), is proposed to address complex issues like limited observations, multicollinearity, and nonlinearity in Chinese Medicine (CM) dose-effect relationship experimental data. MIR-PLS uses a piecewise mapping function based on monotonic cubic splines to model the non-linear inner relations between input and output score vectors. Additionally, a new weight updating strategy (WUS) is developed by leveraging the properties of monotonic functions. The proposed MIR-PLS method was compared with five well-known PLS variants: standard PLS, quadratic PLS (QPLS), error-based QPLS (EB-QPLS), neural network PLS (NNPLS), and spline PLS (SPL-PLS), using CM dose-effect relationship datasets and near-infrared (NIR) spectroscopy datasets. Experimental results demonstrate that MIR-PLS exhibits general applicability, achieving excellent predictive performances in the presence or absence of significant non-linear relationships. Furthermore, the model is not limited to CM dose-effect relationship research and can be applied to other regression tasks.

Satellite mapping reveals phytoplankton biomass's spatio-temporal dynamics and responses to environmental factors in a eutrophic inland lake.

Chlorophyll a (Chla) concentration can be used as an indicator of algal biomass, and the accumulation of algal biomass in water column is essential for the emergence of surface blooms. By using Moderate Resolution Imaging Spectrometer (MODIS) data, a machine learning algorithm was previously developed to assess algal biomass within the euphotic depth (Beu). Here, a long-term Beu dataset of Lake Taihu from 2003 to 2020 was generated to examine its spatio-temporal dynamics, sensitivity to environmental factors, and variations in comparison to the surface algal bloom area. During this period, the daily Beu (total Beu within the whole lake) exhibited temporal fluctuations between 40 and 90 t Chla, with an annual average of 63.32 ± 5.23 t Chla. Notably, it reached its highest levels in 2007 (72.34 t Chla) and 2017 (73.57 t Chla). Moreover, it demonstrated a clear increasing trend of 0.197 t Chla/y from 2003 to 2007, followed by a slight decrease of 0.247 t Chla/y after 2017. Seasonal variation showed a bimodal annual cycle, characterized by a minor peak in March âˆ¼ April and a major peak in July âˆ¼ September. Spatially, the average pixel-based Beu (total Beu of a unit water column) ranged from 21.17 to 49.85 mg Chla, with high values predominantly distributed in the northwest region and low values in the central region. The sensitivity of Beu to environmental factors varies depending on regions and time scales. Temperature has a significant impact on monthly variation (65.73%), while the level of nutrient concentrations influences annual variation (55.06%). Wind speed, temperature, and hydrodynamic conditions collectively influence the spatial distribution of Beu throughout the entire lake. Algal bloom biomass can capture trend changes in two mutant years as well as bimodal phenological changes compared to surface algal bloom area. This study can provide a basis for scientific evaluation of water environment and a reference for monitoring algal biomass in other similar eutrophic lakes.

Boosting the Faradaic Efficiency of Br--Mediated Photoelectrochemical Epoxidation by Local Acidity on α-Fe2O3.

The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value-added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br-/HOBr-mediated method is developed to achieve a near-quantitative selectivity and ≈100% FE of styrene oxide on α-Fe2O3, in which low concentration of Br- as mediator and locally generated acidic micro-environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH-dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.

Hovenia dulcis Fruit Peduncle Polysaccharides Reduce Intestinal Dysbiosis and Hepatic Fatty Acid Metabolism Disorders in Alcohol-Exposed Mice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites-C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)-involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Bias distribution and regulation in photoelectrochemical overall water-splitting cells.

The water oxidation half-reaction at anodes is always considered the rate-limiting step of overall water splitting (OWS), but the actual bias distribution between photoanodes and cathodes of photoelectrochemical (PEC) OWS cells has not been investigated systematically. In this work, we find that, for PEC cells consisting of photoanodes (nickel-modified n-Si [Ni/n-Si] and α-Fe2O3) with low photovoltage (Vph < 1 V), a large portion of applied bias is exerted on the Pt cathode for satisfying the hydrogen evolution thermodynamics, showing a thermodynamics-controlled characteristic. In contrast, for photoanodes (TiO2 and BiVO4) with Vph > 1 V, the bias required for cathode activation can be significantly reduced, exhibiting a kinetics-controlled characteristic. Further investigations show that the bias distribution can be regulated by tuning the electrolyte pH and using alternative half-reaction couplings. Accordingly, a volcano plot is presented for the rational design of the overall reactions and unbiased PEC cells. Motivated by this, an unbiased PEC cell consisting of a simple Ni/n-Si photoanode and Pt cathode is assembled, delivering a photocurrent density of 5.3 ± 0.2 mA cm-2.

Do serum vitamin D levels affect assisted reproductive outcomes and perinatal outcomes in young non-PCOS patients? A retrospective study.

PURPOSE: This study aimed to determine the influence of serum vitamin D levels on assisted reproductive and perinatal outcomes in young non-polycystic ovary syndrome (PCOS) patients. METHODS: A total of 3397 non-PCOS women under 35 years who underwent their first IVF/ICSI cycle at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University, from 2018 to 2019, were included. The women were categorized into two groups based on their serum 25(OH)D concentrations: deficient group [25(OH)D < 50 nmol/L] and non-deficient group [25(OH)D ≥ 50 nmol/L]. Ovulation induction results, clinical pregnancy rate, cumulative live birth rate (CLBR), and perinatal outcomes of both groups were compared. RESULTS: A total of 1113 non-PCOS women had successful pregnancies in their first completed IVF cycle. Comparison of laboratory results between the two groups revealed a significantly higher number of oocytes retrieved in the vitamin D-non-deficient group (15.2 ± 6.8 vs. 14.5 ± 6.7, p = 0.015). After controlling for confounding factors, there was no significant difference in the CLBR between the vitamin D-deficient group and the non-deficient group (71.0%, 1,973/2,778 vs. 69.0%, 427/619, p = 0.314, unadjusted). The prevalence of gestational diabetes mellitus (GDM) was higher in the vitamin D-deficient group than in the vitamin D-non-deficient group in both fresh-cycle singleton live births (3.8% vs. 1.2%) and twin live births (2.3% vs. 1.5%). CONCLUSION: This study demonstrated that vitamin D-deficient group had a lower number of oocytes retrieved than the non-deficient group and a higher prevalence of GDM, suggesting that vitamin D deficiency impacts assisted pregnancies and perinatal outcomes in infertile non-PCOS women. However, further studies are required to confirm these findings.

Global analysis of T-cell groups reveals immunological features and common antigen targets of digestive tract tumors.

BACKGROUND: T cells are key players in the tumor immune microenvironment (TIME), as they can recognize and eliminate cancer cells that express neoantigens derived from somatic mutations. However, the diversity and specificity of T-cell receptors (TCRs) that recognize neoantigens are largely unknown, due to the high variability of TCR sequences among individuals. METHODS: To address this challenge, we applied GLIPH2, a novel algorithm that groups TCRs based on their predicted antigen specificity and HLA restriction, to cluster the TCR repertoire of 1,702 patients with digestive tract cancer. The patients were divided into five groups based on whether they carried tumor-infiltrating or clonal-expanded TCRs and calculated their TCR diversity. The prognosis, tumor subtype, gene mutation, gene expression, and immune microenvironment of these groups were compared. Viral specificity inference and immunotherapy relevance analysis performed for the TCR groups. RESULTS: This approach reduced the complexity of TCR sequences to 249 clonally expanded and 150 tumor-infiltrating TCR groups, which revealed distinct patterns of TRBV usage, HLA association, and TCR diversity. In gastric adenocarcinoma (STAD), patients with tumor-infiltrating TCRs (Patients-TI) had significantly worse prognosis than other patients (Patients-nonTI). Patients-TI had richer CD8+ T cells in the immune microenvironment, and their gene expression features were positively correlated with immunotherapy response. We also found that tumor-infiltrating TCR groups were associated with four distinct tumor subtypes, 26 common gene mutations, and 39 gene expression signatures. We discovered that tumor-infiltrating TCRs had cross-reactivity with viral antigens, indicating a possible link between viral infections and tumor immunity. CONCLUSION: By applying GLIPH2 to TCR sequences from digestive tract tumors, we uncovered novel insights into the tumor immune landscape and identified potential candidates for shared TCRs and neoantigens.

Thyroid-stimulating hormone levels are associated with estradiol levels and impact reproductive outcomes in preconceptionally euthyroid women undergoing their first IVF/ICSI cycles.

PURPOSE: Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women. METHODS: This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements. RESULTS: TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos. CONCLUSION(S): Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins.

TAX1BP1, a multifunctional autophagy adaptor, plays critical roles in different autophagy processes. As an autophagy receptor, TAX1BP1 can interact with RB1CC1, NAP1, and mammalian ATG8 family proteins to drive selective autophagy for relevant substrates. However, the mechanistic bases underpinning the specific interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins remain elusive. Here, we find that there are two distinct binding sites between TAX1BP1 and RB1CC1. In addition to the previously reported TAX1BP1 SKICH (skeletal muscle and kidney enriched inositol phosphatase (SKIP) carboxyl homology)/RB1CC1 coiled-coil interaction, the first coiled-coil domain of TAX1BP1 can directly bind to the extreme C-terminal coiled-coil and Claw region of RB1CC1. We determine the crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex and unravel the detailed binding mechanism of TAX1BP1 SKICH with RB1CC1. Moreover, we demonstrate that RB1CC1 and NAP1 are competitive in binding to the TAX1BP1 SKICH domain, but the presence of NAP1's FIP200-interacting region (FIR) motif can stabilize the ternary TAX1BP1/NAP1/RB1CC1 complex formation. Finally, we elucidate the molecular mechanism governing the selective interactions of TAX1BP1 with ATG8 family members by solving the structure of GABARAP in complex with the non-canonical LIR (LC3-interacting region) motif of TAX1BP1, which unveils a unique binding mode between LIR and ATG8 family protein. Collectively, our findings provide mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins and are valuable for further understanding the working mode and function of TAX1BP1 in autophagy.

Obesity is associated with long-term outcome of catheter ablation of atrial fibrillation in patients with dilated cardiomyopathy.

BACKGROUND: Patients with atrial fibrillation (AF) and dilated cardiomyopathy (DCM) often exhibit cardiac dysfunction and a poor prognosis. However, the specific reasons are unclear. This study aimed to describe the impact of obesity in patients with AF and DCM. METHODS: Seventy-four consecutive patients with AF and DCM were enrolled and classified by body mass index. We measured primary endpoints, including cardiac death, recurrent AF, recurrent atrial tachyarrhythmia and stroke, as well as secondary endpoints. RESULTS: In multivariate analysis, compared to the normal-weight group, the overweight and obese groups had greater incidences of recurrent AF (0.0 vs 30.3 vs 40.0%, respectively, log-rank p = 0.048) and rehospitalisation (9.1 vs 36.4 vs 45.0%, respectively, log-rank p = 0.035). Compared to the normal-weight group, five-year outcomes for primary endpoints were inferior in the overweight and obese groups (18.2 vs 30.3 vs 50.0%, respectively, log-rank p = 0.042). Overweight patients exhibited more benefit in recovery of left ventricular ejection fraction after ablation (from 39.1 to 50.0%, p = 0.005) than the normal-weight group (from 43.1 to 52.3%, p = 0.199) and obese group (from 44.9 to 51.2%, p = 0.216). CONCLUSION: Patients with AF and DCM with overweight or obesity exhibited worse long-term outcomes in recurrent AF than normal-weight patients. However, overweight patients showed the most benefit in cardiac function after ablation.

Acid-Catalyzed Highly Enantioselective Synthesis of α-Amino Acid Derivatives from Sulfinamides and Alkynes.

An enantioselective difunctionalization of activated alkynes using chiral sulfinamide reagents is developed. It is an atom and chirality transfer process that allows for the modular synthesis of optically active α-amino acid derivatives under mild conditions. The reaction proceeds through an acid-catalyzed [2,3]-sigmatropic rearrangement mechanism with predictable stereochemistry and a broad scope.

A controlled non-radical chlorine activation pathway on hematite photoanodes for efficient oxidative chlorination reactions.

Photo(electro)catalytic chlorine oxidation has emerged as a useful method for chemical transformation and environmental remediation. However, the reaction selectivity usually remains low due to the high activity and non-selectivity characteristics of free chlorine radicals. In this study, we report a photoelectrochemical (PEC) strategy for achieving controlled non-radical chlorine activation on hematite (α-Fe2O3) photoanodes. High selectivity (up to 99%) and faradaic efficiency (up to 90%) are achieved for the chlorination of a wide range of aromatic compounds and alkenes by using NaCl as the chlorine source, which is distinct from conventional TiO2 photoanodes. A comprehensive PEC study verifies a non-radical "Cl+" formation pathway, which is facilitated by the accumulation of surface-trapped holes on α-Fe2O3 surfaces. The new understanding of the non-radical Cl- activation by semiconductor photoelectrochemistry is expected to provide guidance for conducting selective chlorine atom transfer reactions.

New research for detecting complex associations between variables with randomness.

Many correlation analysis methods can capture a wide range of functional types of variables. However, the influence of uncertainty and distribution status in data is not considered, which leads to the neglect of the regularity information between variables, so that the correlation of variables that contain functional relationship but subject to specific distributions cannot be well identified. Therefore, a novel correlation analysis framework for detecting associations between variables with randomness (RVCR-CA) is proposed. The new method calculates the normalized RMSE to evaluate the degree of functional relationship between variables, calculates entropy difference to measure the degree of uncertainty in variables and constructs the copula function to evaluate the degree of dependence on random variables with distributions. Then, the weighted sum method is performed to the above three indicators to obtain the final correlation coefficient R. In the study, which considers the degree of functional relationship between variables, the uncertainty in variables and the degree of dependence on the variables containing distributions, cannot only measure the correlation of functional relationship variables with specific distributions, but also can better evaluate the correlation of variables without clear functional relationships. In experiments on the data with functional relationship between variables that contain specific distributions, UCI data and synthetic data, the results show that the proposed method has more comprehensive evaluation ability and better evaluation effect than the traditional method of correlation analysis.

The plasmonic effect of Cu on tuning CO2 reduction activity and selectivity.

Copper (Cu) has been widely used for catalyzing the CO2 reduction reaction (CO2RR), but the plasmonic effect of Cu has rarely been explored for tuning the activity and selectivity of the CO2RR. Herein, we conducted a quantitative analysis on the plasmon-generated photopotential (Ehv) of a Cu nanowire array (NA) photocathode and found that Ehv exclusively reduced the apparent activation energy (Ea) of reducing CO2 to CO without affecting the competitive hydrogen evolution reaction (HER). As a result, the CO production rate was enhanced by 52.6% under plasmon excitation when compared with that under dark conditions. On further incorporation with a polycrystalline Si photovoltaic device, the Cu NA photocathode exhibits good stability in terms of photocurrent and syngas production (CO : H2 = 2 : 1) within 10 h. This work validates the crucial role of the plasmonic effect of Cu on modulating the activity and selectivity of the CO2RR.

Preoperative C-reactive Protein and Other Inflammatory Biomarkers as Predictors of Postoperative Complications in Colorectal Tumor Patients.

Objective: This study aims to explore the predictive value of preoperative C-reactive protein (CRP) and other inflammatory biomarkers: platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) for postoperative complications (infection, diarrhea, etc.) in colorectal tumor patients. Methods: A cohort of 109 colorectal tumor patients who underwent surgical resection for colorectal cancer at the hospital from January 2021 to December 2022 were selected as the research subjects. Patients' postoperative complications were tracked, and they were split into the complication group and the non-complication group. All patients underwent preoperative biochemical tests. Serum levels of CRP, PLR, and NLR were compared between the two groups. The relationship between these markers and postoperative complications in colorectal tumor patients was analyzed. A Logistic regression model was established to analyze their impact on postoperative complications, and a Receiver Operating Characteristic (ROC) curve was drawn to assess predictive value. Results: Among the 109 colorectal tumor patients, 31 cases (28.44%) experienced postoperative complications. The complication group had larger tumor diameters and a higher proportion of open surgeries compared to the non-complication group (P < .05). Serum levels of CRP, PLR, and NLR were higher in the complication group compared to the non-complication group (P < .05). Correlation analysis showed that serum CRP, PLR, and NLR values were positively correlated with postoperative complications in colorectal tumor patients (r > 0, P < .05). The Logistic regression model revealed that high serum CRP levels (95%CI: 1.253-2.503), PLR (95%CI: 1.005-1.041), and NLR values (95%CI: 2.702-20.533) were risk factors for postoperative complications in colorectal tumor patients (OR>1, P < .05). The ROC curve demonstrated that serum CRP levels, PLR, and NLR values had certain predictive values for postoperative complications in colorectal tumor patients (AUC=0.811, 0.789, 0.870), the optimal predictive values were obtained when the cut-off values were set at 5.400 mg/L, 142.790, and 2.485, respectively and combined detection showed even higher predictive values (AUC=0.913). At 1 week post-surgery, the patient's CRP levels, PLR value, and NLR value were significantly lower than pre-surgery (P < .05). Conclusion: Preoperative serum CRP, PLR, and NLR values are closely related to postoperative complications in colorectal tumor patients, and they can be used to predict the risk of postoperative complications in colorectal tumor patients. Clinically, early prediction of postoperative complications in patients can be achieved by measuring the aforementioned indicators, allowing for the implementation of appropriate preventive measures such as detoxification and infection control to improve patient outcomes.

Highly Selective Ammonia Oxidation on BiVO4 Photoanodes Co-catalyzed by Trace Amounts of Copper Ions.

High-efficient photoelectrocatalytic direct ammonia oxidation reaction (AOR) conducted on semiconductor photoanodes remains a substantial challenge. Herein, we develop a strategy of simply introducing ppm levels of Cu ions (0.5-10 mg/L) into NH3 solutions to significantly improve the AOR photocurrent of bare BiVO4 photoanodes from 3.4 to 6.3 mA cm-2 at 1.23 VRHE , being close to the theoretical maximum photocurrent of BiVO4 (7.5 mA cm-2 ). The surface charge-separation efficiency has reached 90 % under a low bias of 0.8 VRHE . This AOR exhibits a high Faradaic efficiency (FE) of 93.8 % with the water oxidation reaction (WOR) being greatly suppressed. N2 is the main AOR product with FEs of 71.1 % in aqueous solutions and FEs of 100 % in non-aqueous solutions. Through mechanistic studies, we find that the formation of Cu-NH3 complexes possesses preferential adsorption on BiVO4 surfaces and efficiently competes with WOR. Meanwhile, the cooperation of BiVO4 surface effect and Cu-induced coordination effect activates N-H bonds and accelerates the first rate-limiting proton-coupled electron transfer for AOR. This simple strategy is further extended to other photoanodes and electrocatalysts.

Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress.

It has been shown that exposure to nanoplastics (MNPs) through inhalation can induce pulmonary toxicity, but the toxicological mechanism of MNPs on the respiratory system remains unclear. Therefore, we explored the toxicological mechanism of exposure to polystyrene nanoplastics (PS-NPs) (0.05, 0.15, 0.2 mg/mL) on BEAS-2B cells. Results revealed that PS-NPs induce oxidative stress, increased apoptosis rate measured by flow cytometry, the key ferroptosis protein (GPX4 and FTH1) reduction, increased iron content, mitochondrial alterations, and increased malondialdehyde (MDA) level. Besides, consistent results were observed in mice exposed to PS-NPs (5 mg/kg/2d, 10 mg/kg/2d). Thus, we proved that PS-NPs induced cell death and lung damage through apoptosis and ferroptosis. In terms of mechanism, the elevation of the endoplasmic reticulum (ER) stress protein expression (IRE1α, PERK, XBP1S, and CHOP) revealed that PS-NPs induce lung damage by activating the two main ER stress pathways. Furthermore, the toxicological effects of PS-NPs observed in this study are attenuated by the ROS inhibitor N-acetylcysteine (NAC). Collectively, NPs-induced apoptosis and ferroptosis are attenuated by NAC via inhibiting the ROS-dependent ER stress in vitro and in vivo. This improves our understanding of the mechanism by which PS-NPs exposure leads to pulmonary injury and the potential protective effects of NAC.

Sevoflurane suppresses colorectal cancer malignancy by modulating ß-catenin ubiquitination degradation via circSKA3.

BACKGROUND: Sevoflurane (SEV), a commonly used inhalational anesthetic, reportedly inhibits colorectal cancer (CRC) malignancy, but whether SEV can inhibit the malignancy of CRC by regulating circular RNAs (circRNAs) remains unclear. Therefore, we aimed to identify specific circRNAs that may be affected by SEV and to investigate their functional roles in CRC. METHODS: RT-qPCR was employed to detect the expression of circRNAs and mRNAs in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to determine the location of circSKA3. Protein expression was assessed by western blot analysis. Function-based in vitro and in vivo experiments, including CCK-8, colony formation, transwell, and apoptosis assays and mouse xenograft tumor models, were conducted using circSKA3-knockdown and circSKA3-overexpression cell lines. RNA immunoprecipitation, RNA pull-down and mass spectrometry analyses were performed to explore the related mechanism. RESULTS: Our findings revealed that SEV could inhibit CRC cell activity, proliferation and migration and promote apoptosis in CRC cells. We found that circSKA3 was upregulated in CRC and associated with poorer survival and that its expression could be reduced by SEV. The overexpression of circSKA3 reversed the effects of SEV on inhibiting cell activity, proliferation and migration and promoting apoptosis. The mechanistic analysis revealed that circSKA3 could bind to the ARM structural domain of ß-catenin and thereby disrupt its interaction with the CK1/GSK3ß/ß-TrCP1 destruction complex, resulting in the ubiquitinated degradation of ß-catenin and the activation of Wnt/ß-catenin signaling. In addition, SEV downregulated circSKA3 in vivo to inhibit tumor growth. CONCLUSIONS: All the results showed that SEV could inhibit CRC progression via circSKA3 by increasing ß-catenin ubiquitination degradation.

Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration.

PURPOSE: Antibody-drug conjugate (ADC) has had a transformative effect on the treatment of many solid tumors, yet it remains unclear how ADCs exert bystander activity in the tumor microenvironment. EXPERIMENTAL DESIGN: Here, we directly visualized and spatiotemporally quantified the intratumor biodistribution and pharmacokinetics of different ADC components by developing dual-labeled fluorescent probes. RESULTS: Mechanistically, we found that tumor penetration of ADCs is distinctly affected by their ability to breach the binding site barrier (BSB) in perivascular regions of tumor vasculature, and bystander activity of ADC can only partially breach BSB. Furthermore, bystander activity of ADCs can work in synergy with coadministration of their parental antibodies, leading to fully bypassing BSBs and enhancing tumor penetration via a two-step process. CONCLUSIONS: These promising preclinical data allowed us to initiate a phase I/II clinical study of coadministration of RC48 and trastuzumab in patients with malignant stomach cancer to further evaluate this treatment strategy in humans.