Examination of primary aromatic amines content in polylactic acid straws and migration into food simulants using SERS with LC-MS.

Polylactic acid (PLA) straws hold eco-friendly potential; however, residual diisocyanates used to enhance the mechanical strength can generate carcinogenic primary aromatic amines (PAAs), posing health risks. Herein, we present a rapid, comprehensive strategy to detecting PAAs in 18 brands of food-grade PLA straws and assessing their migration into diverse food simulants. Surface-enhanced Raman spectroscopy was conducted to rapidly screen straws for PAAs. Subsequently, qualitative determination of migrating PAAs into various food simulants (4 % acetic acid, 10 % ethanol, 50 % ethanol) occurred at 70 °C for 2 h using liquid chromatography-mass spectrometry. Three PAAs including 4,4'-methylenedianiline, 2,4'-methylenedianiline, and 2,4-diaminotoluene were detected in all straws. Specifically, 2,4-diaminotoluene in 50 % ethanol exceeded specific migration limit of 2 µg/kg, raising safety concerns. Notably, PAAs migration to 10 % and 50 % ethanol surpassed that to 4 % acetic acid within a short 2-hour period. Moreover, PLA straws underwent varying degrees of shape changes before and after migration. Straws with poly(butylene succinate) resisted deformation compared to those without, indicating enhanced heat resistance, while poly(butyleneadipate-co-terephthalate) improved hydrolysis resistance. Importantly, swelling study unveiled swelling effect wasn't the primary factor contributing to the increased PAAs migration in ethanol food simulant, as there was no significant disparity in swelling degrees across different food simulants. FT-IR and DSC analysis revealed higher PAAs content in 50 % ethanol were due to highly concentrated polar ethanol disrupting hydrogen bonds and van der Waal forces holding PLA molecules together. Overall, minimizing contact between PLA straws and alcoholic foods is crucial to avoid potential safety risks posed by PAAs.

Jmjd2c maintains the ALDHbri+ cancer stemness with transcription factor SOX2 in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LSCC) is a deadly cancer in the world. Histone demethylase Jmjd2c is a key epigenetic regulator in various tumors, while the molecular mechanism underlying Jmjd2c regulatory in LSCC is still unclear. We used the aldehyde dehydrogenasebright (ALDHbri+) subtype as a research model for cancer stem cells (CSCs) in LSCC and detected the sphere formation ability and the proportion of ALDHbri+ CSCs with Jmjd2c interference and caffeic acid (CA) treatment. Additionally, we carried out bioinformatic analysis on the expression file of Jmjd2c RNAi mice and performed western blotting, qRT-PCR, Co-IP and GST pull-down assays to confirm the bioinformatic findings. Moreover, we generated Jmjd2c-silenced and Jmjd2c-SOX2-silenced ALDHbri+ tumor-bearing BALB/c nude mice to detect the effects on tumor progression. The results showed that Jmjd2c downregulation inhibited the sphere formation and the proportion of ALDHbri+ CSCs. The SOX2 decreased expression significantly in Jmjd2c RNAi mice, and they were positively co-expressed according to the bioinformatic analysis. In addition, SOX2 expression decreased in Jmjd2c shRNA ALDHbri+ CSCs, Jmjd2c and SOX2 proteins interacted with each other. Furthermore, Jmjd2c interference revealed significant blocking effect, and Jmjd2c-SOX2 interference contributed even stronger inhibition on ALDHbri+ tumor progression. The Jmjd2c and SOX2 levels were closely related to the development and prognosis of LSCC patients. This study indicated that Jmjd2c played key roles on maintaining ALDHbri+ CSC activity in LSCC by interacting with transcription factor SOX2. Jmjd2c might be a novel molecule for therapeutic targets and biomarkers in the diagnosis and clinical treatment of lung cancer.

Paradoxical herniation associated with hyperbaric oxygen therapy after decompressive craniectomy: A case report.

BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.

South and Southeast Asia controls black carbon characteristics of Meili Snow Mountains in southeast Tibetan Plateau.

South and Southeast Asia (SSA) emitted black carbon (BC) exerts potential effects on glacier and snow melting and regional climate change in the Tibetan Plateau. In this study, online BC measurements were conducted for 1 year at a remote village located at the terminus of the Mingyong Glacier below the Meili Snow Mountains. The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) was used to investigate the contribution and potential effect of SSA-emitted BC. In addition, variations in the light absorption characteristics of BC and brown carbon (BrC) were examined. The results indicated that the annual mean concentration of BC was 415 ± 372 ngm-3, with the highest concentration observed in April (monthly mean: 930 ± 484 ngm-3). BC exhibited a similar diurnal variation throughout the year, with two peaks observed in the morning (from 8:00 to 9:00 AM) and in the afternoon (from 4:00 to 5:00 PM), with even lower values at nighttime. At a short wavelength of 370 nm, the absorption coefficient (babs) reached its maximum value, and the majority of babs values were < 20 Mm-1, indicating that the atmosphere was not overloaded with BC. At the same wavelength, BrC substantially contributed to babs, with an annual mean of 25.2 % ± 12.8 %. SSA was the largest contributor of BC (annual mean: 51.1 %) in the study area, particularly in spring (65.6 %). However, its contributions reached 20.2 % in summer, indicating non-negligible emissions from activities in other regions. In the atmosphere, the SSA BC-induced radiative forcing (RF) over the study region was positive. While at the near surface, the RF exhibited a significant seasonal variation, with the larger RF values occurring in winter and spring. Overall, our findings highlight the importance of controlling BC emissions from SSA to protect the Tibetan Plateau against pollution-related glacier and snow cover melting.

NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer.

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

Targeting MutT Homolog 1 (MTH1) for Breast Cancer Suppression by Using a Novel MTH1 Inhibitor MA-24 with Tumor-Selective Toxicity.

BACKGROUND: Breast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells need MTH1 for survival. Pharmacological inhibition of MTH1 may be potentially beneficial in the treatment of breast cancer. METHODS: MA-24 was screened by malachite green colorimetric assay for MTH1 inhibitors and the kinetic characteristics of MA-24 were assessed. The features of MA-24's binding with MTH1 were ascertained through molecular docking, and the cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay, and Western blot confirmed the intracellular target and mechanism of MA-24. RESULTS: MA-24 shows potent antitumor bioactivity both in vitro and in vivo. MA-24 competitively inhibited the MTH1 and further induced DNA strand breaks, leading to increased apoptosis of cancer cells depending on the upregulation of the cleaved-caspase 3-cleaved-PARP axis. In particular, MA-24 exhibited a powerful efficacy and safety in vivo (tumor growth inhibition rate: 61.8%). CONCLUSIONS: MA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great potential for the further development MA-24 as an anti-cancer drug.

Flexible microfluidic co-recognition coupled with magnetic enrichment and silent SERS sensing for simultaneous analysis of bacteria in food.

Food safety represents a critical global public health issue, with safety challenges posed by foodborne pathogens garnering extensive attention. Therefore, we introduce a co-recognition, enrichment and sensing (CES) all-in-one strategy for analysis of bacteria with low background and high specificity. This method employs antimicrobial peptide (AMP) functionalized magnetic nanoparticles (MNPs) to enrich bacteria and uses aptamer@Au@PBA (KxMFe(CN)6 (M = Pb and Ni)) NPs as silent SERS tags. When both S. aureus and E. coli O157:H7 are present, the silent SERS probes could specifically label the target bacteria, forming a sandwich-like structure. This binding induces silent Raman shifts (2139 cm-1 and 2197 cm-1), enabling quantification of two bacteria. Coupling with the modular flexible microfluidics and magnetic control slider device, this platform facilitates rapid switching between magnetic loading and elution. The CES SERS method demonstrated linear relationships for both S. aureus and E. coli O157:H7 at 50-1600 cfu mL-1, with detection limits of 14 and 18 cfu mL-1, respectively. The method achieved recovery rates of 85.6-112% and relative standard deviations of 1.5-8.6%. Validation using the ELISA method revealed relative errors between -7.5 and 4.3%. The CES approach has potential applications in food safety, environmental monitoring, and biomedical diagnosis.

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bifunctional Mo2N Nanoparticles with Nanozyme and SERS Activity: A Versatile Platform for Sensitive Detection of Biomarkers in Serum Samples.

The combined application of nanozymes and surface-enhanced Raman scattering (SERS) provides a promising approach to obtain label-free detection. However, developing nanomaterials with both highly efficient enzyme-like activity and excellent SERS sensitivity remains a huge challenge. Herein, we proposed one-step synthesis of Mo2N nanoparticles (NPs) as a "two-in-one" substrate, which exhibits both excellent peroxidase (POD)-like activity and high SERS activity. Its mimetic POD activity can catalyze the 3,3',5,5'-tetramethylbenzidine (TMB) molecule to SERS-active oxidized TMB (ox-TMB) with high efficiency. Furthermore, combining experimental profiling with theory, the mechanism of POD-like activity and SERS enhancement of Mo2N NPs was explored in depth. Benefiting from the outstanding properties of Mo2N NPs, a versatile platform for indirect SERS detection of biomarkers was developed based on the Mo2N NPs-catalyzed product ox-TMB, which acts as the SERS signal readout. The feasibility of this platform was validated using glutathione (GSH) and target antigens alpha-fetoprotein antigen (AFP) and carcinoembryonic antigen (CEA) as representatives of small molecules with a hydroxyl radical (·OH) scavenging effect and proteins with a low Raman scattering cross-section, respectively. The limits of detection of GSH, AFP, and CEA were as low as 0.1 µmol/L, 89.1, and 74.6 pg/mL, respectively. Significantly, it also showed application in human serum samples with recoveries ranging from 96.0 to 101%. The acquired values based on this platform were compared with the standard electrochemiluminescence method, and the relative error was less than ±7.3. This work not only provides a strategy for developing highly active bifunctional nanomaterials but also manifests their widespread application for multiple biomarkers analysis.

HIF­1 and macrophage activation signalling pathways are potential biomarkers of invasive aspergillosis.

Invasive aspergillosis (IA) is a severe disease, the pathogenesis of which remains unclear. The present study aimed to determine the molecular mechanism of IA and to identify potential biomarkers using bioinformatics analysis. The GSE78000 dataset, which includes data from patients with IA and healthy individuals, was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the IA and control groups were identified with the 'affy' package in R software. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases were then used to analyse the function and pathway enrichment of DEGs. The protein-protein interaction network was analysed with the Search Tool for the Retrieval of Interacting Genes (STRING) website. In addition, DEGs were confirmed using reverse transcription-quantitative PCR and western blotting in samples with IA (n=6) and control samples (n=6) collected from the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Henan University of Science and Technology (Luoyang, China). The present study identified 735 DEGs, including 312 upregulated and 423 downregulated genes. Through GO and KEGG analyses of the DEGs, macrophage activation and hypoxia-inducible factor 1 (HIF-1) signalling pathways were revealed to be significantly upregulated and downregulated, respectively, in patients with IA compared with that of the healthy individuals. Subsequently, correlation analysis of macrophage activation and HIF-1 signalling pathways was revealed using correlation as a distance metric for hierarchical clustering correlation analysis. However, there was no protein-protein interaction between the macrophage activity regulation and HIF-1 signalling pathways based on STRING analysis. In summary, the present study identified candidate genes and associated molecules that may be associated to IA and revealed potential biomarkers and therapeutic targets for IA.

Weakened black carbon trans-boundary transport to the Tibetan Plateau during the COVID-19 pandemic.

The lockdowns implemented during the coronavirus disease 2019 (COVID-19) pandemic provide a unique opportunity to investigate the impact of emission sources and meteorological conditions on the trans-boundary transportation of black carbon (BC) aerosols to the Tibetan Plateau (TP). In this study, we conducted an integrative analysis, including in-situ observational data, reanalysis datasets, and numerical simulations, and found a significant reduction in the trans-boundary transport of BC to the TP during the 2020 pre-monsoon season as a result of the lockdowns and restrictive measures. Specifically, we observed a decrease of 0.0211 µgm-3 in surface BC concentration over the TP compared to the 2016 pre-monsoon period. Of this reduction, approximately 6.04 % can be attributed to the decrease in emissions during the COVID-19 pandemic, surpassing the 4.47 % decrease caused by changes in meteorological conditions. Additionally, the emission reductions have weakened the trans-boundary transport of South Asia BC to the TP by 0.0179 µgm-2s-1; indicating that the recurring spring atmospheric pollution from South Asia to the TP will be alleviated through the reduction of anthropogenic emissions. Moreover, it is important to note that BC deposition on glaciers contributes significantly to glacier melting due to its enrichment, posing a threat to the water sustainability of the TP. Therefore, urgent measures are needed to reduce emissions from adjacent regions to preserve the TP as the "Asian Water Tower."

Synergetic Multichiral Covalent Organic Framework for Enantioselective Recognition and Separation.

In enantiomer recognition and separation, a highly enantioselective approach with universal applicability is urgently desired but hard to realize, especially in the case of chiral molecules. To resolve the trade-off between enantioselectivity and universality, a glutathione (GSH) and methylated cyclodextrins (MCD)-functionalized covalent organic framework (GSH-MCD COF) with porosity and abundant chiral surfaces is presented that was designed and synthesized for recognition and separation of various enantiomers. As expected, the GSH-MCD COF can be used as chiral stationary phases for the separation of various enantiomers, including aromatic alcohols, aromatic acids, amides, amino acids, and organic acids, with performance and versatility even superior to some widely used commercial chiral chromatographic columns. Furthermore, the synthesized GSH-MCD COF shows high enantioselectivity for the rapid recognition and identification of enantiomers and chiral metabolites when coupling to Raman spectroscopy. Molecular simulations suggest that the COF provides a confined microenvironment for cyclodextrins and peptides that dictates the separation and recognition capability. This work provides a strategy to synthesize synergetic multichiral COF and achieve separations and recognitions of enantiomers in complex samples.

Novel sulfate solid supported binary Ru-Ir oxides for superior electrocatalytic activity towards OER and CER.

Electrolysis for producing hydrogen powered by renewable electricity can be dramatically expanded by adapting different electrolytes (brine, seawater or pure water), which means the anode materials must stand up to complex electrolyte conditions. Here, a novel catalyst/support hybrid of binary Ru3.5Ir1Ox supported by barium strontium sulfate (BaSrSO4) was synthesized (RuIrOx/BSS) by exchanging the anion ligands of support. The as-synthesized RuIrOx/BSS exhibits compelling oxygen evolution (OER) and chlorine evolution (CER) performances, which affords to 10 mA cm-2 with only overpotential of 244 mV and 38 mV, respectively. The performed X-ray adsorption spectra clearly indicate the presence of an interface charge transfer effect, which results in the assignment of more electrons to the d orbitals of the Ru and Ir sites. The theoretical calculations demonstrated that the electronic structures of the catalytic active sites were modulated to give a lower overpotential, confirming the intrinsically high OER and CER catalytic activity.

Development of composite amine functionalized polyester microspheres for efficient CO2 capture.

In order to reduce the impact of greenhouse gases on the environment, the development of various new CO2 capture materials has become a hot spot. In this work, a novel composite amine solid adsorbent was prepared by simultaneously using tetraethylenepentamine (TEPA) and 2-[2-(dimethylamino) ethoxy] ethanol (DMAEE) for amine functionalization on the polyester microsphere carrier. The introduction of methyl methacrylate (MMA) with high glass transition temperature into the polyester carrier makes the carrier microspheres have high hardness. At the same time, the carrier also contains active epoxy groups and hydrophobic glycidyl methacrylate (GMA, which can undergo ring-opening reaction with composite amines to achieve high-load and low-energy chemical grafting of amines on the carrier. The composite aminated polyester microspheres were used as an efficient adsorbent for CO2 in simulated flue gas. The results show that the synergistic effect of TEPA-DMAEE composite amine system in the adsorbent is beneficial to the improvement of CO2 capture capacity. When the total amine content in the impregnating solution is 45 wt% and the composite amine ratio is TEPA: DMAEE = 6: 4, the CO2 adsorption capacity can reach the optimal value of 2.45 mmol/ g at 70 °C. In addition, the composite amine microsphere adsorbent has cyclic regeneration performance. Importantly, through kinetic fitting, the Avrami kinetic model fits the CO2 adsorption better than the quasi-first-order and quasi-second-order kinetic models, which proves that physical adsorption and chemical adsorption coexist in the adsorption process. This simple, long-term stable and excellent selective separation performance makes amine-functionalized adsorbents have potential application prospects in CO2 capture.