A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Trace Organic Contaminant Removal from Municipal Wastewater by Styrenic ß-Cyclodextrin Polymers.

Trace organic contaminants (TrOCs) present major removal challenges for wastewater treatment. TrOCs, such as perfluoroalkyl and polyfluoroalkyl substances (PFAS), are associated with chronic toxicity at ng L-1 exposure levels and should be removed from wastewater to enable safe reuse and release of treated effluents. Established adsorbents, such as granular activated carbon (GAC), exhibit variable TrOC removal and fouling by wastewater constituents. These shortcomings motivate the development of selective novel adsorbents that also maintain robust performance in wastewater. Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents with demonstrated TrOC removal efficacy. Here, we report a simplified and potentially scalable synthesis of a porous polymer composed of styrene-linked ß-CD and cationic ammonium groups. Batch adsorption experiments demonstrate that the polymer is a selective adsorbent exhibiting complete removal for six out of 13 contaminants with less adsorption inhibition than GAC in wastewater. The polymer also exhibits faster adsorption kinetics than GAC and ion exchange (IX) resin, higher adsorption affinity for PFAS than GAC, and is regenerable by solvent wash. Rapid small-scale column tests show that the polymer exhibits later breakthrough times compared to GAC and IX resin. These results demonstrate the potential for ß-CD polymers to remediate TrOCs from complex water matrices.

Photoinduced Superhydrophilicity of Gd-Doped TiO2 Ellipsoidal Nanoparticles Boosts T1 Contrast Enhancement for Magnetic Resonance Imaging.

The unsatisfactory performance of current gadolinium chelate based T1 contrast agents (CAs) for magnetic resonance imaging (MRI) stimulates the search for better alternatives. Herein, we report a new strategy to substantially improve the capacity of nanoparticle-based T1 CAs by exploiting the photoinduced superhydrophilic assistance (PISA) effect. As a proof of concept, we synthesized citrate-coated Gd-doped TiO2 ellipsoidal nanoparticles (GdTi-SC NPs), whose r1 increases significantly upon UV irradiation. The reduced water contact angle and the increased number of surface hydroxyl groups substantiate the existence of the PISA effect, which considerably promotes the efficiency of paramagnetic relaxation enhancement (PRE) and thus the imaging performance of GdTi-SC NPs. In vivo MRI of SD rats with GdTi-SC NPs further demonstrates that GdTi-SC NPs could serve as a high-performance CA for sensitive imaging of blood vessels and accurate diagnosis of vascular lesions, indicating the success of our strategy.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

Reaction-based fluorescence probes for "turn on" sensing fluoride ions.

Introducing a weak covalent bond into an originally highly fluorescent molecule to create a non-fluorescent probe is able to provide a new way to detect some nucleophilic targets with enhanced sensitivity. Herein, this is the first time that a tetraphenylethene (TPE)-based probe (TPEONO2) bearing a p-nitrobenzenesulfonyl moiety for the sensing of F- ions in aqueous solution via a cleavage reaction of the sulfonyl ester bond to induce aggregation-induced emission (AIE) has been reported.

Electroacupuncture Stimulation Suppresses Postoperative Inflammatory Response and Hippocampal Neuronal Injury.

Postoperative cognitive dysfunction (POCD) is consequence of anesthesia and surgery that primarily affects older people. The prevention and treatment of POCD has drawn an increasing attention in recent decades. Here, we established the animal model mimicked POCD after femoral fracture surgery, and analyze the effect of acupuncture stimulation on postoperative cognitive function after femoral fracture surgery. Compared with the mock group, the cognitive function performance was significantly decreased both in the anaesthesia group and the surgery group, between which the symptoms were more severe in the surgery group. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus were observed in the surgery group, but only peripheral inflammation response was detected in the anaesthesia group. These findings indicated the POCD was the synergistic outcome of anaesthesia and surgical stimulation but with different pathogenic mechanism. The surgery with mental tri-needles (surgery+MTN) group outperformed the surgery group in terms of cognitive function performance. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus was significantly reduced by the electroacupuncture stimulation. Our findings indicated the protection of electroacupuncture form POCD after femoral fracture surgery is related to the inhibition of inflammation response and neuron impairment.

Key role of exopolysaccharide on di-butyl phthalate adsorbing by Lactobacillus plantarum CGMCC18980.

Plasticizers belong to hormone-like substances existing widely in the environment. According to the Environmental Protection Agency of China, they are considered to be the fourth class of toxic chemicals due to their harmful effects on normal endocrine system in human bodies. In the recent published work of our lab, Lactobacillus plantarum CGMCC18980 (strain P1) could reduce the toxicity of di-butyl phthalate (DBP) in rats effectively. The purpose of this study is to further explore the adsorption mechanism of di-butyl phthalate to L. plantarum CGMCC18980, based on optimizing the adsorption conditions. As a consequence, the adsorption effect of L. plantarum CGMCC18980 attributed to relationships between exopolysaccharide, membrane protein, and the cell wall. Experimental results demonstrated that exopolysaccharide and the cell wall were devoted to DBP binding. An obvious adsorption layer was observed outside of L. plantarum CGMCC18980 through scanning electron microscope (SEM) and transmission electron microscope (TEM). The Fourier transform infrared spectroscopy (FTIR) results showed that the functional groups involved in adsorption were mainly C=O, C-N, and C-O, which related to lipids and polysaccharides. Zeta potential analysis indicated that DBP adsorption had no significant relationship with surface charge. These results revealed that exopolysaccharide may be the key factor of strain CGMCC18980 in DBP adsorption. KEY POINTS: • Lactobacillus plantarum CGMCC18980 has the ability to adsorb di-butyl phthalate, reaching to 58.63%. • Exopolysaccharide is considered to play a key role in adsorption process. • Membrane protein, cell wall, and surface charge do not contribute to adsorption.

Hypoxia differentially regulates estrogen receptor alpha in 2D and 3D culture formats.

Hypoxia is a common feature in solid tumors. Clinical samples show a positive correlation between the expression of the hypoxia-inducible factor HIF-1α and estrogen receptor alpha (ERα) and a negative correlation between HIF-1α and hormone sensitivity. Results from monolayer cultures are in contention with clinical observations, showing that ER (+) cell lines no longer express ERα under hypoxic conditions (1% O2). Here, we compared the impact of hypoxia on the ERα signaling pathway for T47D cells in a 2D and 3D culture format. In the 2D format, the cells were cultured as monolayers. In the 3D format, paper-based scaffolds supported cells suspended in a collagen matrix. Using ELISA, Western blot, and immunofluorescence measurements, we show that hypoxia differentially regulates ERα protein levels in a culture environment-dependent manner. In the 2D format, the protein levels are significantly decreased in hypoxia. In the 3D format, the protein levels are maintained in hypoxia. Hypoxia reduced ERα transcriptional activation in both culture formats. These results highlight the importance of considering tissue dimensionality for in vitro studies. They also show that ERα protein levels in hypoxia are not an accurate indicator of ERα transcriptional activity, and confirm that a positive stain for ERα in a clinical sample may not necessarily indicate hormone sensitivity.

Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.

The health risks associated with acute and prolonged exposure to estrogen receptor (ER) modulators has led to a concerted effort to identify and prioritize potential disruptors present in the environment. ER agonists and antagonists are identified with end-point assays, quantifying changes in cellular proliferation or gene transactivation in monolayers of estrogen receptor alpha expressing (ER+) cells upon exposure. While these monolayer cultures can be prepared, dosed, and analyzed in a highly parallelized manner, they are unable to predict the potencies of ER modulators in vivo accurately. Physiologically relevant model systems that better predict tissue- or organ-level responses are needed. To address this need, we describe here a screening platform capable of quantitatively assessing ER modulators in 96 chemically isolated 3D cultures. These cultures are supported in wax-patterned paper scaffolds whose design has improved performance and throughput over previously described paper-based setups. To highlight the potential of paper-based cultures for toxicity screens, we measured the potency of known ER modulators with a luciferase-based reporter assay. We also quantified the proliferation and invasion of two ER+ cell lines in the presence of estradiol. Despite the inability of the current setup to better predict in vivo potencies of ER modulators than monolayer cultures, the results demonstrate the potential of this platform to support increasingly complex and physiologically relevant tissue-like structures for environmental chemical risk assessment.

Eravacycline activity against clinical S. aureus isolates from China: in vitro activity, MLST profiles and heteroresistance.

BACKGROUND: Mortality rates for patients with Staphylococcus aureus (S. aureus) infections have improved only modestly in recent decades and S. aureus infections remain a major clinical challenge This study investigated the in vitro antimicrobial activity of erevacycline (erava) against clinical S. aureus isolates from China, as well as the heteroresistance frequency of erava and sequence types (STs) represented in the sample. RESULTS: A sample of 328 non-duplicate clinical S. aureus isolates, including 138 methecillin-resistant (MRSA) and 190 methecillin-sensitive (MSSA) isolates, were collected retrospectively in China. Erava exhibited excellent in vitro activity (MIC50 ≤ 0.25 mg/L) against MRSA and MSSA, including isolates harboring Tet specific resistance genes. The frequency of erava heteroresistance in MSSA with erava MICs = 0.5 mg/L was 13.79% (4/29); no MRSA with erava MICs ≤0.5 mg/L exhibited heteroresistance. Heteroresistance- derived clones had no 30S ribosome subunit mutations, but their erava MICs (range, 1-4 mg/L) were suppressed dramatically in the presence of efflux protein inhibitors. CONCLUSIONS: Conclusively, erava exhibited excellent in vitro activity against S. aureus, however hints of erava heteroresistance risk and MIC creep were detected, particularly among MSSA with MICs of 0.5 mg/L.

Biofilm formation in erythromycin-resistant Staphylococcus aureus and the relationship with antimicrobial susceptibility and molecular characteristics.

PURPOSE: In this study, we aimed to investigate biofilm formation characteristics in clinical Staphylococcus aureus (S. aureus) isolates with erythromycin (ERY) resistance from China and further analyze their correlations with antimicrobial susceptibility and molecular characteristics. METHODOLOGY: A total of 276 clinical isolates of ERY-resistant S. aureus, including 142 methicillin-resistant S. aureus (MRSA) strains and 134 methicillin-susceptible S. aureus (MSSA) strains, were retrospectively collected in China. Biofilms were determined by crystal violet staining and ERY resistance genes (ermA, ermB and ermC) were detected by polymerase chain reaction. Inducible clindamycin resistance was examined by D test and multilocus sequence typing, and clonal complexes (CCs) based on housekeeping genes were further determined. RESULTS: The frequency of biofilm formation among ERY-resistant S. aureus was 40.9% (113/276) in total and no significant difference was found for the frequency of biofilm formation between ERY-resistant MRSA and ERY-resistant MSSA (44.4% vs 37.3%, P > 0.05). In ERY-resistant MRSA isolates, the frequency of biofilm formation in ermA-positive, gentamicin-resistant and ciprofloxacin-resistant isolates was higher than that in ermA-negative, gentamicin-sensitive and ciprofloxacin-sensitive isolates, respectively (63.9% vs 23.6%, P < 0.01; 60.3% vs 27.5%, P < 0.01; 65.2% vs 26.3%, P < 0.01). In addition, tetracycline resistance facilitated biofilm formation in both ERY-resistant MRSA and MSSA and the frequency of biofilm formation in CC239- or CC7S. aureus isolates with ERY resistance was significantly higher compared with that in CC59S. aureus (both P < 0.01). CONCLUSION: The ermA gene, and gentamicin, ciprofloxacin and tetracycline resistance facilitate biofilm formation in ERY-resistant MRSA isolates and, moreover, ERY-resistant S. aureus isolates with positive biofilm formation exhibited clonality clustering regarding CC239 and CC7.

Stereodivergent synthesis of all the four stereoisomers of antidepressant reboxetine.

Chiral amino alcohol-copper(ii) catalysts Cu-L1c and Cu-ent-L1c were utilized to promote the diastereoselective nitroaldol reactions of chiral aldehydes (S)-3 or (R)-3 with nitromethane, which respectively led to the preferential formation of certain stereoisomer for nitro diol derivatives 4. Using this catalytic protocol, all the four stereoisomers of the antidepressant reboxetine were divergently prepared. The highest overall yield of this synthetic route reached up to 30.5% from aldehyde (S)-3.

Near-infrared light-responsive composite microneedles for on-demand transdermal drug delivery.

This study presents near-infrared (NIR) light-responsive polymer-nanostructure composite microneedles used for on-demand transdermal drug delivery. Silica-coated lanthanum hexaboride (LaB6@SiO2) nanostructures were incorporated into polycaprolactone microneedles, serving as an NIR absorber. When the microneedles were irradiated with NIR light, light-to-heat transduction mediated by the LaB6@SiO2 nanostructures caused the microneedle melting at 50 °C. This increased the mobility of the polymer chains, enabling drug release from the matrix. Drug release from the microneedles was evaluated for four laser on/off cycles. In each cycle, the samples were irradiated until the temperature reached 50 °C for 3 min (laser on); the laser was then turned off for 30 min (laser off). The results showed that light-induced phase transition in the polymer triggered drug release from the melted microneedles. A stepwise drug-release behavior was observed after multiple cycles of NIR light exposure. No notable drug leakage was found in the off state. This NIR-light-triggerable device exhibits excellent reproducibility, low off-state leakage, and noninvasive triggerability and, thus, represents an advance in transdermal delivery technology.

A chiral gold nanocluster Au20 protected by tetradentate phosphine ligands.

The chirality of a gold nanocluster can be generated from either an intrinsically chiral inorganic core or an achiral inorganic core in a chiral environment. The first structural determination of a gold nanocluster containing an intrinsic chiral inorganic core is reported. The chiral gold nanocluster [Au20(PP3)4]Cl4 (PP3=tris(2-(diphenylphosphino)ethyl)phosphine) has been prepared by the reduction of a gold(I)-tetraphosphine precursor in dichloromethane solution. Single-crystal structural determination reveals that the cluster molecular structure has C3 symmetry. It consists of a Au20 core consolidated by four peripheral tetraphosphines. The Au20 core can be viewed as the combination of an icosahedral Au13 and a helical Y-shaped Au7 motif. The identity of this Au20 cluster is confirmed by ESI-MS. The chelation of multidentate phosphines enhances the stability of this Au20 cluster.

Perfluoroalkyl acid adsorption by styrenic ß-cyclodextrin polymers, anion-exchange resins, and activated carbon is inhibited by matrix constituents in different ways.

Perfluoroalkyl acids (PFAAs) are ubiquitous environmental contaminants of global concern, and adsorption processes are the most widely used technologies to remove PFAAs from water. However, there remains little data on the ways that specific water matrix constituents inhibit the adsorption of PFAAs on different adsorbents. In this study, we evaluated the adsorption of 13 PFAAs on two styrene-functionalized ß-cyclodextrin (StyDex) polymers, an activated carbon (AC), and an anion-exchange resin (AER) in the absence and presence of specific water matrix constituents (16 unique water matrices) in batch experiments. All four adsorbents exhibited some extent of adsorption inhibition in the presence of inorganic ions and/or humic acid (HA) added as a surrogate for natural organic matter. Two PFAAs (C5-C6 perfluorocarboxylic acids (PFCAs)) were found to exhibit relatively weak adsorption and five PFAAs (C6-C8 perfluorosulfonic acids (PFSAs) and C9-C10 PFCAs) were found to exhibit relatively strong adsorption on all four adsorbents across all matrices. Adsorption inhibition was the greatest in the presence of Ca2+ (direct site competition) and HA (direct site competition and pore blockage) for AC, NO3- (direct site competition) and Ca2+ (chemical complexation) for the AER, and SO42- (compression of the double layer) for the StyDex polymers. The pattern of adsorption inhibition of both StyDex polymers were similar to each other but different from AC and AER, which demonstrates the distinctive PFAA adsorption mechanism on StyDex polymers. The unique performance of each type of adsorbent confirms unique adsorption mechanisms that result in unique patterns of adsorption inhibition in the presence of matrix constituents. These insights could be used to develop models to predict the performance of these adsorbents in real water matrices and afford rational selection of adsorbents based on water chemistry for specific applications.

Structural Features of Styrene-Functionalized Cyclodextrin Polymers That Promote the Adsorption of Perfluoroalkyl Acids in Water.

Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents for the removal of per- and polyfluoroalkyl substances (PFAS) from contaminated water sources, including contaminated groundwater, drinking water, and wastewater. We previously reported porous, styrene-functionalized ß-cyclodextrin (StyDex) polymers derived from radical polymerization with vinyl comonomers. Because of the versatility of these polymerizations, StyDex polymer compositions are tunable, which facilitates efforts to establish structure-adsorption relationships and to discover improved materials. Here, we evaluate the material properties and PFAS adsorption of 20 StyDex derivatives with varied comonomer structure and loading, regiochemistry of styrene placement on the CD monomer, and CD size. A StyDex polymer containing N,N'-dimethylbutyl ammonium ions exhibited the most effective PFAS adsorption in batch experiments. Furthermore, a StyDex polymer containing ß-CD exhibited size-selective host-guest interactions with perfluoroalkyl acids (PFAAs) and neutral contaminants in aqueous electrolyte when compared to similar polymers containing either α-CD or γ-CD. Polymers based on ß-CD monomers with an average of seven styrene groups randomly positioned over the 21 available hydroxyl groups performed similarly to those based on a ß-CD monomer functionalized regiospecifically at each of the seven 6' positions. The former ß-CD monomer is prepared in a single step from unmodified ß-CD, so the ability to use it without compromising performance demonstrates promise for developing economically competitive adsorbents. These results offered important insights into structure-adsorption properties of StyDex polymers and will inform the design of improved StyDex formulations.

Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

Long-term ambient ozone exposure and childhood asthma, rhinitis, eczema, and conjunctivitis: A multi-city study in China.

Evidence on the link of long-term exposure to ozone (O3) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children.