Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children's Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes.

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

Efficacy and safety of salvage endoscopy in the treatment of residual or recurrent colorectal neoplasia after endoscopic resection: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of salvage endoscopy for residual or recurrence of colorectal tumors after endoscopic resection. METHODS: Multiple databases including PubMed, EMBASE and the Cochrane Library were searched to screen for eligible studies and perform data extraction and pooled analysis. RESULTS: Sixteen studies on salvage endoscopy for residual or recurrent colorectal cancer after endoscopic resection were included, covering approximately 994 patients. The results of the meta-analysis demonstrated that salvage endoscopic therapy for residual or recurrent colorectal tumors following endoscopic resection achieved an en bloc resection rate of 92% (95% CI 0.85-0.97; I2 = 91%) and an R0 resection rate of 82% (95% CI 0.75-0.87; I2 = 78%). The rates of intraoperative or postoperative bleeding and perforation were 10%/1% and 5%/2%, and the recurrence rate was 2%. CONCLUSIONS: Salvage endoscopic resection is an effective and safe treatment strategy for residual or recurrent colorectal tumors after endoscopic resection.

The deubiquitinating enzyme USP4 regulates BRCA1 stability and function.

BRCA1 plays a suppressive role in breast tumorigenesis. Ubiquitin-dependent degradation is a common mechanism that regulates BRCA1 protein stability, and several ubiquitin ligases involved have been identified. However, the deubiquitinating enzyme for BRCA1 remains less defined. Here, we report that the deubiquitinase USP4 interacts with, deubiquitinates and stabilizes BRCA1, maintaining the protein level of BRCA1. USP4 knockdown results in a decreased BRCA1 protein level, impairment in homologous recombination mediated double-stranded break repair, and increased genome instability, and confers resistance to DNA damage-inducing agents and PARP inhibitors. Ectopic expression of USP4 stabilizes BRCA1 and reverse the effects caused by USP4 knockdown. Moreover, USP4 is low expressed in human breast cancer tissues and its low expression correlates with poorer survival of patients. Furthermore, we identified several loss-of-function mutations of USP4 in human gynecological cancers, the catalytic activity of which or their interaction with BRCA1 is disrupted. Together, we reveal that USP4 is a deubiquitinase for BRCA1. USP4 positively regulates the stability and function of BRCA1 through de-ubiquitination, and plays important role in the suppression of breast cancer.

Predicting influenza-like illness trends based on sentinel surveillance data in China from 2011 to 2019: A modelling and comparative study1.

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

Hepatic polypeptide nutrient solution improves high-cholesterol diet-induced rats with nonalcoholic fatty liver disease by activating AMP-activated protein kinase signaling pathway.

Hepatic polypeptide nutrient solution (HP) is a mixture of hepatoprotective peptides derived from fresh porcine liver with various effects. However, the role and mechanisms of HP in nonalcoholic fatty liver disease (NAFLD) are still not well understood. We investigated the effects of HP NAFLD rats induced by high-cholesterol diet (HCD) and its underlying mechanisms. Rats were provided with HCD for 4 weeks and then received HP or metformin after 2 weeks of HCD feeding. The study found that HP reduced cholesterol and triglyceride levels in rats with NAFLD (all p < .05). Histopathological examination also showed that HP improved the liver lesions induced by the HCD diet. Furthermore, the oxidative stress and inflammatory responses of NAFLD rats treated with HP were also improved. In addition, it was discovered that HP triggered the activation of AMPK and decreased the expression of SREBP-1c and FAS while enhancing the expression of PPAR α and CPT-1 in liver. These findings indicated that HP might have therapeutic potential for NAFLD, possibly via activating AMPK signaling pathway.

Regulation-driven changes in PM2.5 sources in China from 2013 to 2019, a critical review and trend analysis.

Identifying changes in source-specific fine particles (PM2.5) over time is essential for evaluating the effectiveness of regulatory measures and informing future policy decisions. After the extreme haze events in China during 2013-14, more comprehensive and stringent policies were implemented to combat PM2.5 pollution. To determine the effectiveness of these policies, it is necessary to assess the changes in the specific source types to which the regulations pertain. Multiple studies have been conducted over the past decade to apportion PM2.5. The purpose of this study was to explore the available literature and conduct a critical review of the reliable results. In total, 5008 articles were screened, but only 48 studies were included for further analysis given our inclusion criteria including covering a monitoring period of ≥1 year and having enough speciation data to provide mass closure. Using these studies, we analyzed temporal and spatial trends across China from 2013 to 2019. We observed the overall decrease in the concentration contributions from all main source categories. The reductions from industry, coal and heavy oil combustion, and the related secondary sulfate were more notable, especially from 2013 to 2016-17. The contributions from biomass burning initially decreased but then increased slightly after 2016 in some locations despite new constraints on agricultural and household burning practices. Although the contributions from vehicle emissions and related secondary nitrate decreased, they gradually became the primary contributors to PM2.5 by ~2017. Despite the substantial improvements achieved by the air pollution regulation implementations, further improvements in air quality will require additional aggressive actions, especially those targeting vehicular emissions. Ultimately, source apportionment studies based on extended duration, fixed-site sampling are recommended to provide a more thorough understanding of the sources impacting areas and transformations in PM2.5 sources prompted by regulatory actions.

Dynamic alterations of flavor, functional nutrients, and microbial community during fermentation of different animal milk kefirs.

Kefir is a traditional dairy beverage, usually made from cow or goat milk fermented with kefir grains, and has many health benefits. To elucidate the fermentation patterns of animal milk kefirs during the fermentation process and find the optimal milk types, cow, camel, goat, and donkey milk were fermented with kefir grains for 0, 1, 3, 5, and 7 days. Volatile and non-volatile metabolites and microbial changes were dynamically monitored. The results showed that volatile flavor substances were massively elevated in four kefirs on days 1-3. Lipids and carbohydrates gradually decreased, while amino acids, small peptides, and tryptophan derivatives accumulated during fermentation in four kefirs. Besides, four kefirs had similar alterations in Lactobacillus and Acetobacter, while some distinctions existed in low-abundance bacteria. Association analysis of microorganisms and volatile and non-volatile metabolites also revealed the underlying fermentation mechanism. This study found that appropriately extending the fermentation time contributed to the accumulation of some functional nutrients. Furthermore, goat and donkey milk could be the better matrices for kefir fermentation.

Solar-assisted selective separation and recovery of precious group metals from deactivated air purification catalysts.

The mitigation of environmental and energy crises could be advanced by reclaiming platinum group precious metals (PGMs) from decommissioned air purification catalysts. However, the complexity of catalyst composition and the high chemical inertness of PGMs significantly impede this process. Consequently, recovering PGMs from used industrial catalysts is crucial and challenging. This study delves into an environmentally friendly approach to selectively recover PGMs from commercial air purifiers using photocatalytic redox technology. Our investigation focuses on devising a comprehensive strategy for treating three-way catalysts employed in automotive exhaust treatment. By meticulously pretreating and modifying reaction conditions, we achieved noteworthy results, completely dissolving and separating rhodium (Rh), palladium (Pd), and platinum (Pt) within a 12-h time frame. Importantly, the solubility selectivity persists despite the remarkably similar physicochemical properties of Rh, Pd, and Pt. To bolster the environmental sustainability of our method, we harness sunlight as the energy source to activate the photocatalysts, facilitating the complete dissolution of precious metals under natural light irradiation. This eco-friendly recovery approach demonstrated on commercial air purifiers, exhibits promise for broader application to a diverse range of deactivated air purification catalysts, potentially enabling implementation on a large scale.

Oral Synergism of Egg-White-Derived Peptides (EWDP) and Curcumin for Colitis Mitigation via Polysaccharide/Cyclodextrin Metal-Organic Framework-Based Assemblies.

Recently, oral deliverable strategies of multiple nutraceuticals for ulcerative colitis (UC) mitigation have attracted increasing attention. This study aimed to fabricate facile oral assemblies loaded with egg-white-derived peptides (EWDP) and curcumin based on carboxymethyl chitosan (CMCS) and an γ-cyclodextrin metal-organic framework (MOF). Herein, outer CMCS could coassemble with EWDP (both nutraceuticals and building blocks) into cobweb-like fibrils to promote bridging with inner MOF via coordinative noncovalent interactions (hydrogen bonding, hydrophobic interaction, and electrostatic interaction). Compared with conventional γ-cyclodextrin/MOF-based composites, the above coassembly could also endow the biocompatible assemblies with superior nanoscale colloidal properties, processing applicability (curcumin storage stability, bioaccessibility, and aqueous solubility), and bioactivity. Moreover, the oral synergism of EWDP and curcumin (initially nonsynergistic) for UC mitigation was achieved by alleviating inflammatory damage and gut microbiota imbalance. Overall, the novel assemblies could be a promising amplifier and platform to facilitate oral formulations of various nutraceuticals for food processing and UC relief.

Application of online to offline teaching mode in the training of non-anesthesiology residents in the department of anesthesiology: a randomized, controlled trial.

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology. Trial design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University. Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups. Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p < 0.01). Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness.

A Streamlined and Standardized Procedure for Generating High-Titer, High-Quality Adeno-Associated Virus Vectors Utilizing a Cell Factory Platform.

Preclinical gene therapy research, particularly in rodent and large animal models, necessitates the production of AAV vectors with high yield and purity. Traditional approaches in research laboratories often involve extensive use of cell culture dishes to cultivate HEK293T cells, a process that can be both laborious and problematic. Here, a unique in-house method is presented, which simplifies this process with a specific cell factory (or cell stacks, CF10) platform. An integration of polyethylene glycol/aqueous two-phase partitioning with iodixanol gradient ultracentrifugation improves both the yield and purity of the generated AAV vectors. The purity of the AAV vectors is verified through SDS-PAGE and silver staining, while the ratio of full to empty particles is determined using transmission electron microscopy (TEM). This approach offers an efficient cell factory platform for the production of AAV vectors at high yields, coupled with an improved purification method to meet the quality demands for in vivo studies.

Recent developments in synthesis of attapulgite composite materials for refractory organic wastewater treatment: a review.

Attapulgite clay, due to its unique crystalline hydrated magnesium-aluminium silicate composition and layer-chain structure, possesses exceptional adsorption and catalytic properties, which enable it or its composites to be utilized as adsorbents and catalysts for wastewater treatment. But the drawbacks of attapulgite are also very obvious, such as relatively low specific surface area (compared to traditional adsorbents such as activated carbon and activated alumina), easy aggregation, and difficulty in dispersion. In order to fully utilize and improve the performance of attapulgite, researchers have conducted extensive research on its modification, but few specialized works have comprehensively evaluated the synthesis, applications and challenges for attapulgite-based composite materials in refractory organic wastewater treatments. This paper provides a comprehensive review of controllable preparation strategies, characterization methods and mechanisms of attapulgite-based composite materials, as well as the research progress of these materials in refractory organic wastewater treatment. Based on this review, constructive recommendations, such as deep mechanism analysis from molecular level multi-functional attapulgite-based material developments, and using biodegradable materials in attapulgite-based composites, were proposed.

Research Progress on the Correlation Between Hypertension and Gut Microbiota.

Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.

A two-photon fluorescent probe for highly selective detection of Cys over GSH and Hcy based on the Michael addition and transcyclization mechanism and its application in bioimaging and protein straining in SDS-PAGE.

BACKGROUND: Cysteine (Cys), glutathione (GSH), and homocysteine (Hcy), as three major biothiols are involved in a variety of physiological processes and play a crucial role in plant growth. Abnormal levels of Cys can cause plants to fail to grow properly. To date, although a very large number of fluorescent probes have been reported for the detection of biothiols, very few of them can be used for the selective discrimination of Cys from GSH and Hcy due to their structural similarity, and only a few of them can be used for plant imaging. RESULTS: Here, three fluorescent probes (o-/m-/p-TMA) based on TMN fluorophore and the ortho-/meta-/para-substituted maleimide recognition groups were constructed to investigate the selective response effect of Cys. Compared to the o-/m-TMA, p-TMA can selectively detect Cys over GSH and Hcy with a rapid response time (10 min) and a low detection limit (0.26 µM). The theoretical calculation confirmed that the intermediate p-TMA-Cys-int has shorter interatomic reaction distances (3.827 Å) compared to o-/m-TMA-Cys (5.533/5.287 Å), making it more suitable for further transcyclization reactions. Additionally, p-TMA has been employed for selective tracking of exogenous and endogenous Cys in Arabidopsis thaliana using both single-/two-photon fluorescence imaging. Furthermore, single cell walls produced obvious two-photon fluorescence signals, indicating that p-TMA can be used for high-concentration Cys analysis in single cells. Surprisingly, p-TMA can be used as a fluorescent dye for protein staining in SDS-PAGE with higher sensitivity (7.49 µg/mL) than classical Coomassie brilliant blue (14.11 µg/mL). SIGNIFICANCE: The outstanding properties of p-TMA make it a promising multifunctional molecular tool for the highly selective detection of Cys over GSH and Hcy in various complex environments, including water solutions, zebrafish, and plants. Additionally, it has the potential to be developed as a fluorescent dye for a simple and fast SDS-PAGE fluorescence staining method.

Preparation of Rehmanniae Radix Praeparata polysaccharide iron(III) complex and evaluation of its biological activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron(III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Efficient characterizations of multiphoton states with an ultra-thin optical device.

Metasurface enables the generation and manipulation of multiphoton entanglement with flat optics, providing a more efficient platform for large-scale photonic quantum information processing. Here, we show that a single metasurface optical device would allow more efficient characterizations of multiphoton entangled states, such as shadow tomography, which generally requires fast and complicated control of optical setups to perform information-complete measurements, a demanding task using conventional optics. The compact and stable device here allows implementations of general positive operator valued measures with a reduced sample complexity and significantly alleviates the experimental complexity to implement shadow tomography. Integrating self-learning and calibration algorithms, we observe notable advantages in the reconstruction of multiphoton entanglement, including using fewer measurements, having higher accuracy, and being robust against experimental imperfections. Our work unveils the feasibility of metasurface as a favorable integrated optical device for efficient characterization of multiphoton entanglement, and sheds light on scalable photonic quantum technologies with ultra-thin optical devices.

Single-cell analysis defines highly specific leukemia-induced neutrophils and links MMP8 expression to recruitment of tumor associated neutrophils during FGFR1 driven leukemogenesis.

BACKGROUND: Leukemias driven by activated, chimeric FGFR1 kinases typically progress to AML which have poor prognosis. Mouse models of this syndrome allow detailed analysis of cellular and molecular changes occurring during leukemogenesis. We have used these models to determine the effects of leukemia development on the immune cell composition in the leukemia microenvironment during leukemia development and progression. METHODS: Single cell RNA sequencing (scRNA-Seq) was used to characterize leukemia associated neutrophils and define gene expression changes in these cells during leukemia progression. RESULTS: scRNA-Seq revealed six distinct subgroups of neutrophils based on their specific differential gene expression. In response to leukemia development, there is a dramatic increase in only two of the neutrophil subgroups. These two subgroups show specific gene expression signatures consistent with neutrophil precursors which give rise to immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Analysis of gene expression in these precursor cells identified pathways that were specifically upregulated, the most pronounced of which involved matrix metalloproteinases Mmp8 and Mmp9, during leukemia progression. Pharmacological inhibition of MMPs using Ilomastat preferentially restricted in vitro migration of neutrophils from leukemic mice and led to a significantly improved survival in vivo, accompanied by impaired PMN-MDSC recruitment. As a result, levels of T-cells were proportionally increased. In clinically annotated TCGA databases, MMP8 was shown to act as an independent indicator for poor prognosis and correlated with higher neutrophil infiltration and poor pan-cancer prognosis. CONCLUSION: We have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.

ROS-mediated NRF2/p-ERK1/2 signaling-involved mitophagy contributes to macrophages activation induced by CdTe quantum dots.

Cadmium telluride (CdTe) quantum dots (QDs) have garnered significant attention for tumor imaging due to their exceptional properties. However, there remains a need for further investigation into their potential toxicity mechanisms and corresponding enhancements. Herein, CdTe QDs were observed to accumulate in mouse liver, leading to a remarkable overproduction of IL-1ß and IL-6. Additionally, there was evidence of macrophage infiltration and activation following exposure to 12.5 µmol/kg body weight of QDs. To elucidate the underlying mechanism of macrophage activation, CdTe QDs functionalized with 3-mercaptopropionic acid (MPA) were utilized. In vitro experiments revealed that 1.0 µM MPA-CdTe QDs activated PINK1-dependent mitophagy in RAW264.7 macrophages. Critically, the autophagic flux remained unimpeded, as demonstrated by the absence of p62 accumulation, LC3 turnover assay results, and successful fusion of autophagosomes with lysosomes. Mechanically, QDs increased reactive oxygen species (ROS) and mitoROS by damaging both mitochondria and lysosomes. ROS, in turn, inhibited NRF2, resulting in the phosphorylation of ERK1/2 and subsequent activation of mitophagy. Notably, 1.0 µM QDs disrupted lysosomes but autophagic flux was not impaired. Eventually, the involvement of the ROS-NRF2-ERK1/2 pathway-mediated mitophagy in the increase of IL-1ß and IL-6 in macrophages was confirmed using Trolox, MitoTEMPO, ML385, specific siRNAs, and lentivirus-based interventions. This study innovatively revealed the pro-inflammatory rather than anti-inflammatory role of mitophagy in nanotoxicology, shedding new light on the mechanisms of mitochondrial disorders induced by QDs and identifying several molecular targets to comprehend the toxicological mechanisms of CdTe QDs.

Endoscopic submucosal dissection versus surgery for T1b esophageal carcinoma: a single-center retrospective study.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery, especially for T1b SESCC. This study compared the overall survival (OS), disease-free survival (DSS), recurrence-free survival (RFS), and complication rates of both, to evaluate the value of ESD in patients with T1b SESCC. METHODS: We reviewed patients who underwent ESD (n = 47) or surgery (n = 73) for T1b SESCC at Affiliated Hospital of Nanjing University of Chinese Medicine from 2009 to 2021. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion and elderly people. RESULTS: In the ESD and surgery groups, the overall mortality rates were 0/100 and 12.3/100 person years, incidence rates of recurrence were 2.13/100 and 11/100 person years, respectively. Kaplan-Meier survival analysis revealed no significant different in OS, DSS and RFS. Charlson comorbidity index (CCI) and depth of submucosal invasion were identified as risk factors for cancer recurrence in multivariate analysis. For elderly people, no significant differences were found in OS, DSS and RFS between different treatments. CONCLUSION: ESD are related to lower complication rates and shorter hospital stay than surgery in long-term outcomes for patients with pT1b SESCC. But in pT1b-SM2 patients, we still need long-term follow-up.