Bevel-edge epitaxy of ferroelectric rhombohedral boron nitride single crystal.

Within the family of two-dimensional dielectrics, rhombohedral boron nitride (rBN) is considerably promising owing to having not only the superior properties of hexagonal boron nitride1-4-including low permittivity and dissipation, strong electrical insulation, good chemical stability, high thermal conductivity and atomic flatness without dangling bonds-but also useful optical nonlinearity and interfacial ferroelectricity originating from the broken in-plane and out-of-plane centrosymmetry5-23. However, the preparation of large-sized single-crystal rBN layers remains a challenge24-26, owing to the requisite unprecedented growth controls to coordinate the lattice orientation of each layer and the sliding vector of every interface. Here we report a facile methodology using bevel-edge epitaxy to prepare centimetre-sized single-crystal rBN layers with exact interlayer ABC stacking on a vicinal nickel surface. We realized successful accurate fabrication over a single-crystal nickel substrate with bunched step edges of the terrace facet (100) at the bevel facet (110), which simultaneously guided the consistent boron-nitrogen bond orientation in each BN layer and the rhombohedral stacking of BN layers via nucleation near each bevel facet. The pure rhombohedral phase of the as-grown BN layers was verified, and consequently showed robust, homogeneous and switchable ferroelectricity with a high Curie temperature. Our work provides an effective route for accurate stacking-controlled growth of single-crystal two-dimensional layers and presents a foundation for applicable multifunctional devices based on stacked two-dimensional materials.

Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway.

BACKGROUND: Despite radiotherapy ability to significantly improve treatment outcomes and survival in triple-negative breast cancer (TNBC) patients, acquired resistance to radiotherapy poses a serious clinical challenge. Protein disulfide isomerase exists in endoplasmic reticulum and plays an important role in promoting protein folding and post-translational modification. However, little is known about the role of protein disulfide isomerase family member 4 (PDIA4) in TNBC, especially in the context of radiotherapy resistance. METHODS: We detected the presence of PDIA4 in TNBC tissues and paracancerous tissues, then examined the proliferation and apoptosis of TNBC cells with/without radiotherapy. As part of the validation process, xenograft tumor mouse model was used. Mass spectrometry and western blot analysis were used to identify PDIA4-mediated molecular signaling pathway. RESULTS: Based on paired clinical specimens of TNBC patients, we found that PDIA4 expression was significantly higher in tumor tissues compared to adjacent normal tissues. In vitro, PDIA4 knockdown not only increased apoptosis of tumor cells with/without radiotherapy, but also decreased the ability of proliferation. In contrast, overexpression of PDIA4 induced the opposite effects on apoptosis and proliferation. According to Co-IP/MS results, PDIA4 prevented Tax1 binding protein 1 (TAX1BP1) degradation by binding to TAX1BP1, which inhibited c-Jun N-terminal kinase (JNK) activation. Moreover, PDIA4 knockdown suppressed tumor growth xenograft model in vivo, which was accompanied by an increase in apoptosis and promoted tumor growth inhibition after radiotherapy. CONCLUSIONS: The results of this study indicate that PDIA4 is an oncoprotein that promotes TNBC progression, and targeted therapy may represent a new and effective anti-tumor strategy, especially for patients with radiotherapy resistance.

Silver Nanowires-Based Flexible Gold Electrode Overcoming Interior Impedance of Nanomaterial Electrodes.

In the development of nanomaterial electrodes for improved electrocatalytic activity, much attention is paid to the compositions, lattice, and surface morphologies. In this study, a new concept to enhance electrocatalytic activity is proposed by reducing impedance inside nanomaterial electrodes. Gold nanodendrites (AuNDs) are grown along silver nanowires (AgNWs) on flexible polydimethylsiloxane (PDMS) support. The AuNDs/AgNWs/PDMS electrode affords an oxidative peak current density of 50 mA cm-2 for ethanol electrooxidation, a value ≈20 times higher than those in the literature do. Electrochemical impedance spectroscopy (EIS) demonstrates the significant contribution of the AgNWs to reduce impedance. The peak current densities for ethanol electrooxidation are decreased 7.5-fold when the AgNWs are electrolytically corroded. By in situ surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT) simulation, it is validated that the ethanol electrooxidation favors the production of acetic acid with undetectable CO, resulting in a more complete oxidation and long-term stability, while the AgNWs corrosion greatly decreases acetic acid production. This novel strategy for fabricating nanomaterial electrodes using AgNWs as a charge transfer conduit may stimulate insights into the design of nanomaterial electrodes.

Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

TP53 to mediate immune escape in tumor microenvironment: an overview of the research progress.

Increasing evidence suggests that key cancer-causing driver genes continue to exert a sustained influence on the tumor microenvironment (TME), highlighting the importance of immunotherapeutic targeting of gene mutations in governing tumor progression. TP53 is a prominent tumor suppressor that encodes the p53 protein, which controls the initiation and progression of different tumor types. Wild-type p53 maintains cell homeostasis and genomic instability through complex pathways, and mutant p53 (Mut p53) promotes tumor occurrence and development by regulating the TME. To date, it has been wildly considered that TP53 is able to mediate tumor immune escape. Herein, we summarized the relationship between TP53 gene and tumors, discussed the mechanism of Mut p53 mediated tumor immune escape, and summarized the progress of applying p53 protein in immunotherapy. This study will provide a basic basis for further exploration of therapeutic strategies targeting p53 protein.

Exploring the relationship between malnutrition and the systemic immune-inflammation index in older inpatients: a study based on comprehensive geriatric assessment.

BACKGROUND: Malnutrition is a prevalent and major challenge among senior citizens, possibly due to the continual low-grade inflammatory state of the body. A novel inflammatory parameter, the systemic immune-inflammation index (SII), is highly valuable in evaluating and predicting the prognosis of a wide range of diseases. This study aims to explore the significance of the SII in assessing malnutrition in older inpatients. METHODS: This retrospective study included 500 senior hospitalized patients who met the inclusion and exclusion criteria from the Comprehensive Geriatric Assessment database of the First Hospital of Jilin University. The Mini-Nutritional Assessment (MNA) questionnaire was used to evaluate the nutritional status of patients. The SII was calculated using complete blood counts, and we performed natural logarithm transformation of the SII [ln(SII)]. Multivariable logistic regression analysis was used to identify the association between ln(SII) and malnutrition. To ensure the stability of the findings, a sensitivity analysis was conducted. RESULTS: The 500 patients had a mean age of 77.29 ± 9.85 years, and 68.6% were male. In accordance with the MNA, 30.4% of the patients were malnourished or at risk of malnutrition, and patients in this group had considerably greater levels of ln(SII) than patients with adequate nutrition (P < 0.001). The optimum ln(SII) cutoff value for patients with malnutrition or at risk of malnutrition was 6.46 (SII = 635.87) with 46.7% sensitivity and 80.2% specificity [95% CI: 0.613-0.721, AUC: 0.667, P < 0.001]. Multivariable logistic regression demonstrated that ln(SII) was an independent risk factor for the risk of malnutrition or malnutrition in older individuals (OR 3.984, 95% CI: 2.426-6.543, P < 0.001). Other metrics from the geriatric comprehensive assessment, including body mass index, calf circumference, fat ratio, activities of daily living and instrumental activities of daily living, and geriatric depression scale scores, were also independently correlated with nutritional status. CONCLUSIONS: According to our research, a high SII is an independent predictor of older inpatient malnutrition, and the SII aids in screening for malnutrition and may be a potential target for intervention. Comprehensive geriatric assessment parameters such as BMI, calf circumference, fat ratio, activities of daily living and depression were also linked to malnutrition.

High-efficient nutrient removal in a single-stage electrolysis-integrated sequencing batch biofilm reactor (E-SBBR) for low C/N sanitary sewage treatment.

To efficiently remove nutrients from low C/N sanitary sewage by conventional biological process is challenging due to the lack of sufficient electron donors. A novel electrolysis-integrated sequencing batch biofilm reactor (E-SBBR) was established to promote nitrogen and phosphorus removal for sanitary sewage with low C/N ratios (3.5-1.5). Highly efficient removal of nitrogen (>79%) and phosphorus (>97%) was achieved in the E-SBBR operating under alternating anoxic/electrolysis-anoxic/aerobic conditions. The coexistence of autotrophic nitrifiers, electron transfer-related bacteria, and heterotrophic and autohydrogenotrophic denitrifiers indicated synergistic nitrogen removal via multiple nitrogen-removing pathways. Electrolysis application induced microbial anoxic ammonia oxidation, autohydrogenotrophic denitrification and electrocoagulation processes. Deinococcus enriched on the electrodes were likely to mediate the electricity-driven ammonia oxidation which promoted ammonia removal. PICRUSt2 indicated that the relative abundances of key genes (hyaA and hyaB) associated with hydrogen oxidation significantly increased with the decreasing C/N ratios. The high autohydrogenotrophic denitrification rates during the electrolysis-anoxic period could compensate for the decreased heterotrophic rates resulting from insufficient carbon sources and nitrate removal was dramatically enhanced. Electrocoagulation with iron anode was responsible for phosphorus removal. This study provides insights into mechanisms by which electrochemically assisted biological systems enhance nutrient removal for low C/N sanitary sewage.

Response of nutrients removal efficiency, enzyme activities and microbial community to current and voltage in a bio-electrical anammox system.

The effects of different current intensities and voltage levels on nutrient removal performance and microbial community evolution in a Bio-Electrical Anammox (BEA) membrane bioreactor (MBR) were evaluated. The nitrogen removal efficiency increased with the current intensity within the range of 64-83 mA, but this improvement was limited at the current further increased. The phosphorus removal in the BEA MBR was attributed to the release of Fe2+, which was closely associated with the applied current to the electrodes. Heme c concentration, enzyme activities, and specific anammox activity exhibited a decreasing trend, while the functional denitrification genes showed a positive correlation with rising voltage. The nitrogen removal efficiency of the BEA system initially increased and then decreased with the voltage rose from 1.5V to 3.5V, peaking at 2.0V of 94.02% ± 1.19%. Transmission electron microscopy and flow cytometry results indicated that accelerated cell apoptosis/lysis led to an irreversible collapse of the biological nitrogen removal system at 3.5V. Candidatus Brocadia was the predominant anammox bacteria in the BEA system. In contrast, closely related Candidatus Kuenenia and Chloroflexi bacteria were gradually eliminated in electrolytic environment. The abundances of Proteobacteria-affiliated denitrifiers were increased with the voltage rising since the organic matter released by the cell apoptosis/lysis was accelerated at a high voltage level.

Evaluation of mandibular motion in adolescents with skeletal class II division 1 malocclusion during mandibular advancement using clear functional aligners: a prospective study.

BACKGROUND: This study aimed to evaluate the characteristics of mandibular protrusive condylar trajectory in adolescents with skeletal Class II Division 1 malocclusion and the changes of condylar trajectory during mandibular advancement (MA) treatment using clear functional aligners. METHODS: This prospective study consisted of a cross-sectional study and a longitudinal study. In cross-sectional study, sixty-one adolescents were divided into two groups: Class I (n = 30) and Class II Division 1 (n = 31). The condylar trajectory was measured and compared using the Mann-Whitney U test. The longitudinal study was the MA treatment group using clear functional aligner and consisted of 16 participants from Class II Division 1group. The condylar trajectory was collected at three-time points: pre-treatment (T1), during MA treatment at approximately 3 months (T2, 105.6 days average), and at the end of MA treatment (T3, 237.6 days average). The changes at T1, T2, and T3, as well as the symmetry between the left and right condyles across all groups, were examined using the Wilcoxon paired test. RESULTS: A greater increase in the anteroposterior displacement and space displacement during protrusive movements was observed in the Class II Division 1 group compared with that in the Class I group, with a large difference being observed in the left and right condylar movements. The condylar anteroposterior displacement and space displacement decreased significantly at T2 and increased significantly at T3; however, no significant difference was observed between T1 and T3. A significant difference was observed between the condylar movement on the left and right sides at T1; however, no significant difference was observed at T2 and T3. CONCLUSIONS: Adolescents with Class II Division 1 malocclusion had higher protrusive capacity than those with Class I. Moreover, their left and right condylar motion was more asymmetric. The range of condyle motion decreased first and then increased during MA therapy, and the left and right condyle movement became more symmetrical, which may be the adaptive response of neuromuscular function to the changes in jaw position.

Lnc-PKNOX1-1 inhibits tumor progression in cutaneous malignant melanoma by regulating NF-κB/IL-8 axis.

Cutaneous malignant melanoma is one of the most lethal cutaneous malignancies. Accumulating evidence has demonstrated the potential influence of long non-coding RNAs (lncRNAs) in biological behaviors of melanoma. Herein, we reported a novel lncRNA, lnc-PKNOX1-1 and systematically studied its functions and possible molecular mechanisms in melanoma. Reverse transcription-quantitative PCR assay showed that lnc-PKNOX1-1 was significantly decreased in melanoma cells and tissues. Low lnc-PKNOX1-1 expression was significantly correlated with invasive pathological type and Breslow thickness of melanoma. In vitro and in vivo experiments showed lnc-PKNOX1-1 dramatically inhibited melanoma cell proliferation, migration and invasion. Mechanically, protein microarray analysis suggested that interleukin-8 (IL-8) was negatively regulated by lnc-PKNOX1-1 in melanoma, which was confirmed by western blot and ELISA. Western blot analysis also showed that lnc-PKNOX1-1 could promote p65 phosphorylation at Ser536 in melanoma. Subsequent rescue assays proved IL-8 overexpression could partly reverse the tumor-suppressing function of lnc-PKNOX1-1 overexpression in melanoma cells, indicating that lnc-PKNOX1-1 suppressed the development of melanoma by regulating IL-8. Taken together, our study demonstrated the tumor-suppressing ability of lnc-PKNOX1-1 in melanoma, suggesting its potential as a novel diagnostic biomarker and therapeutic target for melanoma.

Near-field antenna measurement based on Rydberg-atom probe.

Current near-field antenna measurement methods are commonly based on metal probes, with the accuracy limited and hard to be optimized due to the drawbacks they suffered, such as large volume, severe metal reflection/interference and complex circuit signal processing in parameter extracting. In this work, a novel method is proposed based on Rydberg atom in the near-field antenna measurement, which can offer a higher accuracy due to its intrinsic character of traceability to electric field. Replacing the metal probe in near-field measurement system by Rydberg atoms contained in a vapor cell (probe), amplitude- and phase- measurements on a 2.389 GHz signal launched out from a standard gain horn antenna are conducted on a near-field plane. They are transformed to far-field pattern and agree well with simulated results and measured results by using a traditional metal probe method. A high precision in longitudinal phase testing with an error below 1.7% can be achieved.

Tunable frequency of a microwave mixed receiver based on Rydberg atoms under the Zeeman effect.

Researchers are interested in the sensor based on Rydberg atoms because of its broad testing frequency range and outstanding sensitivity. However, the discrete frequency detection limits its further employment. We expand the frequency range of microwaves using Rydberg atoms under the Zeeman effect. In such a scheme, the magnetic field is employed as a tool to split and modify adjacent Rydberg level intervals to realize tunable frequency measurement over 100 MHz under 0-31.5 Gauss magnetic field. In this frequency range, the microwave has a linear dynamic variation range of 63 dB, and has achieved a sensitivity of 11.72 µV cm-1Hz-1/2 with the minimum detectable field strength of 17.2 µV/cm.. Compared to the no magnetic field scenario, the sensitivity would not decrease. By theoretical analysis, in a strong magnetic field, the tunable frequency range can be much larger than 100 MHz. The proposed method for achieving tunable frequency measurement provides a crucial tool in radars and communication.

Non-specific LIPID TRANSFER PROTEIN 1 enhances immunity against tobacco mosaic virus in Nicotiana benthamiana.

Plant non-specific lipid transfer proteins (nsLTPs) are small, cysteine-rich proteins that play significant roles in biotic and abiotic stress responses; however, the molecular mechanism of their functions against viral infections remains unclear. In this study, we employed virus-induced gene-silencing and transgenic overexpression to functionally analyse a type-I nsLTP in Nicotiana benthamiana, NbLTP1, in the immunity response against tobacco mosaic virus (TMV). NbLTP1 was inducible by TMV infection, and its silencing increased TMV-induced oxidative damage and the production of reactive oxygen species (ROS), compromised local and systemic resistance to TMV, and inactivated the biosynthesis of salicylic acid (SA) and its downstream signaling pathway. The effects of NbLTP1-silencing were partially restored by application of exogenous SA. Overexpressing NbLTP1 activated genes related to ROS scavenging to increase cell membrane stability and maintain redox homeostasis, confirming that an early ROS burst followed by ROS suppression at the later phases of pathogenesis is essential for resistance to TMV infection. The cell-wall localization of NbLTP1 was beneficial to viral resistance. Overall, our results showed that NbLTP1 positively regulates plant immunity against viral infection through up-regulating SA biosynthesis and its downstream signaling component, NONEXPRESSOR OF PATHOGENESIS-RELATED 1 (NPR1), which in turn activates pathogenesis-related genes, and by suppressing ROS accumulation at the later phases of viral pathogenesis.

Exosomal ACADM sensitizes gemcitabine-resistance through modulating fatty acid metabolism and ferroptosis in pancreatic cancer.

This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms through RNA-sequencing and mass spectrometry. We sought to understand the connection between the exosomal Medium-chain acyl-CoA dehydrogenase (ACADM) level and the reaction to gemcitabine in vivo and in patients with PC. We employed loss-of-function, gain-of-function, metabolome mass spectrometry, and xenograft models to investigate the effect of exosomal ACADM in chemoresistance in PC. Our results showed that the molecules involved in lipid metabolism in exosomes vary between PC cells with different gemcitabine sensitivity. Exosomal ACADM (Exo-ACADM) was strongly correlated with gemcitabine sensitivity in vivo, which can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. Moreover, ACADM was found to regulate the gemcitabine response by affecting ferroptosis through Glutathione peroxidase 4 (GPX4) and mevalonate pathways. It was also observed that ACADM increased the consumption of unsaturated fatty acids and decreased intracellular lipid peroxides and reactive oxygen species (ROS) levels. In conclusion, this research suggests that Exo-ACADM may be a viable biomarker for predicting the responsiveness of patients to chemotherapy.

Quantification of ectopic fat storage in the liver and pancreas using six-point Dixon MRI and its association with insulin sensitivity and ß-cell function in patients with central obesity.

OBJECTIVES: To assess the association of ectopic fat deposition in the liver and pancreas quantified by Dixon magnetic resonance imaging (MRI) with insulin sensitivity and ß-cell function in patients with central obesity. MATERIALS AND METHODS: A cross-sectional study of 143 patients with central obesity with normal glucose tolerance (NGT), prediabetes (PreD), and untreated type 2 diabetes mellitus (T2DM) was conducted between December 2019 and March 2022. All participants underwent routine medical history taking, anthropometric measurements, and laboratory tests, including a standard glucose tolerance test to quantify insulin sensitivity and ß-cell function. The fat content in the liver and pancreas was measured with MRI using the six-point Dixon technique. RESULTS: Patients with T2DM and PreD had a higher liver fat fraction (LFF) than those with NGT, while those with T2DM had a higher pancreatic fat fraction (PFF) than those with PreD and NGT. LFF was positively correlated with homeostatic model assessment of insulin resistance (HOMA-IR), while PFF was negatively correlated with homeostatic model assessment of insulin secretion (HOMA-ß). Furthermore, using a structured equation model, we found LFF and PFF to be positively associated with glycosylated hemoglobin via HOMA-IR and HOMA-ß, respectively. CONCLUSIONS: In patients with central obesity, the effects of LFF and PFF on glucose metabolism. were associated with HOMA-IR and HOMA-ß, respectively. Ectopic fat storage in the liver and pancreas quantified by MR Dixon imaging potentially plays a notable role in the onset ofT2DM. CLINICAL RELEVANCE STATEMENT: We highlight the potential role of ectopic fat deposition in the liver and pancreas in the development of type 2 diabetes in patients with central obesity, providing valuable insights into the pathogenesis of the disease and potential targets for intervention. KEY POINTS: • Ectopic fat deposition in the liver and pancreas is associated with T2DM. • T2DM and prediabetes patients had higher liver and pancreatic fat fractions than normal individuals. • The results provide valuable insights into pathogenesis of T2DM and potential targets for intervention.

Ginseng-derived nanoparticles potentiate immune checkpoint antibody efficacy by reprogramming the cold tumor microenvironment.

Cold tumor microenvironment (TME) marked with low effector T cell infiltration leads to weak response to immune checkpoint inhibitor (ICI) treatment. Thus, switching cold to hot TME is critical to improve potent ICI therapy. Previously, we reported extracellular vesicle (EV)-like ginseng-derived nanoparticles (GDNPs) that were isolated from Panax ginseng C.A. Mey and can alter M2 polarization to delay the hot tumor B16F10 progression. However, the cold tumor is more common and challenging in the real world. Here, we explored a combinatorial strategy with both GDNPs and PD-1 (programmed cell death protein-1) monoclonal antibody (mAb), which exhibited the ability to alter cold TME and subsequently induce a durable systemic anti-tumor immunity in multiple murine tumor models. GDNPs enhanced PD-1 mAb anti-tumor efficacy in activating tumor-infiltrated T lymphocytes. Our results demonstrated that GDNPs could reprogram tumor-associated macrophages (TAMs) to increase CCL5 and CXCL9 secretion for recruiting CD8+ T cells into the tumor bed, which have the synergism to PD-1 mAb therapy with no detected systemic toxicity. In situ activation of TAMs by GDNPs may broadly serve as a facile platform to modulate the suppressive cold TME and optimize the PD-1 mAb immunotherapy in future clinical application.

Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer.

Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3). siSTAT3 loaded KEVs (STAT3/KEVs) could be easily endowed with EGFR targeting ability (STAT3/EKEVs) and fluorescence by surface modification with tailor-making aptamer through hydrophobic interaction. STAT3/EKEVs with a controlled size of 186 nm displayed excellent stability, high specificity and good cytotoxicity towards EGFR over-expressing and mutant PC9-GR4-AZD1 cells. Intriguingly, the systemic administration of STAT3/EKEVs significantly suppressed subcutaneous PC9-GR4-AZD1 tumor xenografts in nude mice by STAT3 mediated apoptosis. This safe and robust KEVs has emerged as the next generation of gene delivery platform for NSCLC therapy after multiple drug-resistance.

Sludge biodrying coupled with photocatalysis improves the degradation of extracellular polymeric substances.

The efficiency of sludge dewatering is limited by extracellular polymeric substances (EPS) during biodrying. This study investigated the effect of photocatalysis-mediated EPS degradation on sludge dewatering performance during the sludge biodrying process. The photocatalysis of municipal sludge was first carried out to choose a cost-efficient catalyst. Then sludge biodrying tests were performed using TiO2-coated amendment (TCA) and uncoated amendment (TUCA) as the control. Municipal sludge photocatalysis results showed that using TiO2 could efficiently degrade carbohydrates and proteins in the EPS within 60 min. After 20-day biodrying, photocatalysis significantly promoted a reduction in the moisture content and EPS by 17.64% and 6.88%, respectively. The surface-enhanced Raman scattering (SERS) intensities of the C-C-O symmetric stretching vibration peak of D-lactose and the C-S stretching vibration peak of cysteine were significantly decreased by approximately 33.19% and 44.76%, respectively, indicating that photocatalysis indeed promoted the reduction of polysaccharides and cysteine in the EPS, especially after the thermophilic phase. The hydrophilic amino acid content decreased by 23.02%, verifying that photocatalysis could improve EPS hydrophobicity. Consequently, municipal sludge biodrying coupled with photocatalysis promotes sludge EPS degradation and enhances sludge dewaterability, improving the efficiency of sludge biodrying.

Decorating Channel Walls in Metal-Organic Frameworks with Crown Ethers for Efficient and Selective Separation of Radioactive Strontium(II).

Nuclear accidents and the improper disposal of nuclear wastes have led to serious environmental radioactive pollutions. The rational design of adsorbents for the highly efficient separation of strontium(II) is essential in treating nuclear waste and recovering radioactive strontium resources. Metal-organic frameworks (MOFs) are potential materials for the separation of aqueous metal ions owing to their designable structure and tunable functionality. Herein, a novel 3D MOF material MOF-18Cr6, in which 1D channels are formed using 18-crown-6-ether-containing ligands as channel walls, is fabricated for strontium(II) separation. In contrast to traditional MOFs designed by grafting functional groups in the framework pores, MOF-18Cr6 possesses regular 18-crown-6-ether cavities on the channel walls, which not only can transport and intake strontium(II) via the channels, but also prevent blockage of the channels after the binding of strontium(II). Consequently, the functional sites are fully utilized to achieve a high strontium(II) removal rate of 99.73 % in simulated nuclear wastewater. This study fabricates a highly promising adsorbent for the separation of aqueous radioactive strontium(II), and more importantly, can provide a new strategy for the rational design of high-performance MOF adsorbents for separating target substances from complex aqueous environments.

Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.