HIF-1α/METTL1/m7G axis is involved in CRC response to hypoxia.

BACKGROUND: In recent years, many studies have confirmed that hypoxia and hypoxia inducible factor (HIF)-1α drive the development of colorectal cancer (CRC). HIF-1α also modulates epitranscriptomic remodeling to regulate cancer development. However, the mechanism by which RNA methylation is altered under hypoxic conditions and the underlying regulatory mechanisms in CRC remain unclear. METHODS: Here, seven common types of modifications of mRNA and tRNA were quantitated using liquid chromatography-tandem mass spectrometry. To validate the robustness of the profiling data, modifications that were consistently altered across the three CRC cell lines under hypoxia were validated via dot blot analysis. Then, 10 enzymes that could regulate the abundance of three RNA modifications in tRNA were measured in CRC cells after hypoxia treatment using quantitative real-time polymerase chain reaction. Furthermore, the regulatory role of HIF-1α in the expression of methyltransferase 1 (METTL1) under hypoxic conditions was confirmed using METTL1 promoter activity assays and HIF-1α small interfering RNA (siRNA). The binding capacity of HIF-1α to each hypoxia response element (HRE) in the promoter of METTL1 was investigated by performing Chromatin immunoprecipitation assay (ChIP). RESULTS: Abundance of RNA modifications was altered more consistently and significantly in tRNA than in mRNA under hypoxic conditions. In addition, the abundance of N7-methyleguanosine (m7G) modification in tRNA decreased significantly under hypoxic conditions. As a methyltransferase of the m7G modification in tRNA, the expression of METTL1 mRNA was drastically downregulated under hypoxic conditions. Mechanistically, suppression of HIF-1α by siRNA upregulated the METTL1 promoter activity. Furthermore, ChIP showed that HIF-1α could bind with an HRE in the promoter region of METTL1, indicating that METTL1 is a direct target of HIF-1α in CRC cells under hypoxic conditions. CONCLUSIONS: Our study revealed that the abundance of the m7G modification in tRNA was drastically reduced in CRC cells dependent on the HIF-1α-mediated inhibition of METTL1 transcription under hypoxic conditions.

Focal ischemic myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), ischemic myocardial fibrosis assessed by late gadolinium enhancement (I-LGE) using cardiovascular magnetic resonance (CMR) have been reported. However, the clinical significance of I-LGE has not been completely understood. We aim to evaluate the I-LGE differ phenotypically from HCM without LGE or nonischemic myocardial fibrosis assessed by late gadolinium enhancement (NI-LGE) in the left ventricle (LV). METHODS: The patients with HCM whom was underwent CMR were enrolled, using cine cardiac magnetic resonance to evaluate LV function and LGE to detect the myocardial fibrosis. Three groups were assorted: 1) HCM without LGE; 2) HCM with LGE involved the subendocardial layer was defined as I-LGE; 3) HCM with LGE not involved the subendocardial layer was defined as NI-LGE. RESULTS: We enrolled 122 patients with HCM in the present study. LGE was detected in 58 of 122 (48%) patients with HCM, and 22 (18%) of patients reported I-LGE. HCM with I-LGE had increased higher left ventricular mass index (LVMI) (P < 0.0001) than HCM with NI-LGE or without LGE. In addition, HCM with I-LGE had a larger LV end- systolic volume (P = 0.045), lower LV ejection fraction (LVEF) (P = 0.026), higher LV myocardial mass (P < 0.001) and thicker LV wall (P < 0.001) more than HCM without LGE alone. The I-LGE were significantly associated with LVEF (OR: 0.961; P = 0.016), LV mass (OR: 1.028; P < 0.001), and maximal end-diastolic LVWT (OR: 1.567; P < 0.001). On multivariate analysis, LVEF (OR: 0.948; P = 0.013) and maximal end-diastolic LVWT (OR: 1.548; P = 0.001) were associated with higher risk for I-LGE compared to HCM without LGE. Noticeably, the maximal end-diastolic LVWT (OR: 1.316; P = 0.011) was the only associated with NI-LGE compared to HCM without LGE. CONCLUSIONS: I-LGE is not uncommon in patients with HCM. HCM with I-LGE was associated with significant LV hypertrophy, extensive LGE and poor LV ejection fraction. We should consider focal ischemic myocardial fibrosis when applying LGE to risk stratification for HCM.

Design method for engineering the initial structure of a spectrometer.

A well-considered initial structure plays a key role in the design of an exceptional spectrometer. Previously, the design method for the optical initial structure (MOIS) that has only focused on the optical properties based on simple imaging formulas and coma-free conditions has been extensively researched. However, as the shape and size of any optical component are not considered for the MOIS, the optical parameters before and after optimization are very different, which results in a loss of reference value of the initial structure. In order to address the aforementioned issues, a more efficient design method for engineering initial structure (MEIS) of the spectrometer is proposed, where not only the above optical properties are considered but also the relative position and size of any optical component in order to avoid the interference between the optical components. For the MEIS, three important anti-interference conditions between components are deduced through ray tracing, and the relevant imaging formulas are derived by geometric optics, which leads to the rapid calculation of component parameters and the acquisition of an initial structure satisfying the corresponding design requirements by setting reasonable spacing margins. To verify the validity of the MEIS, a wide-band high-resolution spectrometer system with a large CCD Toucan 216 is designed within a wavelength range of 700-1000 nm and a resolution of 0.5 nm. Compared with the MOIS, the positions of each component in the MEIS are more rationalized, which significantly eliminates the complex optimization processes. For the MEIS, changes only in the position of the image plane occur with minimal variations in the axial and vertical wheelbase (less than 0.5 mm) as well as the deflection angle (only 0.5°), with favorable evaluation indices. The MEIS has an important reference value for the rapid and efficient design of excellent spectrometers.

Fear of cancer recurrence in adolescent patients with malignant bone tumors: a cross-section survey.

BACKGROUND: Adolescent malignant-bone tumor patients' fear of cancer recurrence is a significant psychological issue, and exploring the influencing factors associated with fear of cancer recurrence in this population is important for developing effective interventions. This study is to investigate the current status and factors influencing fear of cancer recurrence (FCR) related to malignant bone-tumors in adolescent patients, providing evidence for future targeted mental health support and interventions. DESIGN: A cross-sectional survey. METHODS: In total, 269 adolescent malignant-bone tumor cases were treated at two hospitals in Zhejiang Province, China from January 2023 to December 2023. Patients completed a General Information Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Family Hardiness Index (FHI), and a Simple Coping Style Questionnaire (SCSQ). Univariate and multivariable logistic regressions analysis were used to assess fear of cancer recurrence. RESULTS: A total of 122 (45.4%) patients experienced FCR (FoP-Q-SF ≥ 34). Logistic regression analysis analyses showed that per capita-monthly family income, tumor stage, communication between the treating physician and the patient, patient's family relationships, family hardiness a positive coping score, and a negative coping score were the main factors influencing FCR in these patients (P < 0.05). CONCLUSIONS: FCR in malignant-bone tumor adolescent patients is profound. Healthcare professionals should develop targeted interventional strategies based on the identified factors, which affect these patients; helping patients increase family hardiness, helping patients to positively adapt, and avoid negative coping styles.

Two-sample Mendelian randomization analysis of the relationship between periodontitis and risk of upper gastrointestinal cancers.

PURPOSE: The aim of the present study is to explore the possible association between periodontitis and upper gastrointestinal (UGI) cancers, including esophageal and gastric cancers, utilizing the Mendelian randomization method. METHODS: In this research, we utilized the Mendelian randomization method to examine the causal association between periodontitis and UGI cancers. Genome-wide association studies data for periodontitis were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium, while UGI cancers' data were accessed from FinnGen's Biobank. After rigorously screening instrumental variables for periodontitis, we analyzed them with UGI cancers primarily using the inverse variance weighted. Finally, to identify outliers, the results were subjected to a leave-one-out sensitivity analysis. RESULTS: Inverse variance weighted (fixed effect) results revealed that periodontitis is a risk factor for gastric cancer (OR = 1.7735, 95% CI: 1.1576 to 2.7170, P = 0.0085). As for esophageal cancer, no statistically significant correlation was observed. Furthermore, no outliers were detected in any of the results. CONCLUSION: Our two-sample Mendelian randomization study obviously demonstrates a significant positive association between periodontitis and gastric cancer, while no statistically significant correlation was found for esophageal cancer.

Cu-Catalyzed Methylenation of Alcohols with N-Methyl Amide as a Sustainable Methylene Reagent.

Herein, we report a new approach to methylenation of alcohols using N-methyl amide as a sustainable methylene reagent; the N-methyl delivers the methylene group. This new reagent is easily prepared and stable to both air and moisture. Furthermore, the final byproduct of this methylene reagent can be recycled in excellent yields and then reused in methylenation reactions upon treating with CH3I.

Purinergic signaling in thyroid disease.

It is known that thyroid hormones play pivotal roles in a wide variety of pathological and physiological events. Thyroid diseases, mainly including hyperthyroidism, hypothyroidism, and thyroid cancer, are highly prevalent worldwide health problems and frequently associated with severe clinical manifestations. However, etiology of hyperthyroidism, hypothyroidism, and thyroid cancer is not fully understood. Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the recognition and degradation of extracellular nucleotides and adenosine. It has been established that purinergic signaling modulates pathways in a wide range of physiopathological conditions including hypertension, diabetes, hepatic diseases, psychiatric and neurodegeneration, rheumatic immune diseases, and cancer. More recently, the purinergic system is found to exist in thyroid gland and play an important role in the pathophysiology of thyroid diseases. Therefore, throughout this review, we focus on elaborating the changes in purinergic receptors, extracellular enzymes, and extracellular nucleotides and adenosine in hyperthyroidism, hypothyroidism, and thyroid cancer. Profound understanding of the relationship between the purinergic signaling with thyroid diseases provides a promising research area for insights into the molecular basis of thyroid diseases and also develops new and exciting insights into the treatment of thyroid diseases, especially thyroid cancer.

Identification of key genes in sepsis by WGCNA.

When the body damages its own tissues in response to an infection, sepsis develops. Medical treatments are limited. It's important to understand the molecular mechanism behind sepsis pathogenesis and identify potential molecular treatment targets. We made two modules based on how genes work together by using WGCNA analysis. The light-green GSE131761 module and the blue GSE137342 module had the strongest links to sepsis. A gene ontology (GO) analysis showed that most of the genes in the lightgreen module were involved in the inflammatory response, specific granule, and immune receptor activity. Most of the genes in the blue module were significantly more likely to have the GO terms proteasomal protein catabolic process, ubiquitin ligase complex, and ubiquitin-like protein transferase activity. The KEGG analysis showed that the genes in module lightgreen were mostly involved in the TNF signaling pathway, while the genes in module blue were mostly involved in the Prion disease pathway. There were two hub genes that were found. In the end, ANKRD22 and VNN1 were singled out as crucial genes. This study used WGCNA to investigate sepsis-associated susceptibility modules and genes. Our study identified two modules and two key genes as essential components in sepsis etiology, which may improve our understanding of its molecular mechanisms.

Trophic Transfer of Halogenated Organic Pollutants in a Wetland Food Web: Insights from Compound-Specific Nitrogen Isotope of Amino Acids and Food Source Analysis.

A trophic position (TP) model (TPmix model) that simultaneously considered trophic discrimination factor and ßGlu/Phe variations was developed in this study and was first applied to investigate the trophic transfer of halogenated organic pollutants (HOPs) in wetland food webs. The TPmix model characterized the structure of the wetland food web more accurately and significantly improved the reliability of TMF compared to the TPbulk, TPAAs, and TPsimmr models, which were calculated based on the methods of stable nitrogen isotope analysis of bulk, traditional AAs-N-CSIA, and weighted ßGlu/Phe, respectively. Food source analysis revealed three interlocking food webs (kingfisher, crab, and frogs) in this wetland. The highest HOP biomagnification capacities (TMFmix) were found in the kingfisher food web (0.24-82.0), followed by the frog (0.08-34.0) and crab (0.56-11.7) food webs. The parabolic trends of TMFmix across combinations of log KOW in the frog food web were distinct from those of aquatic food webs (kingfisher and crab), which may be related to differences in food web composition and HOP bioaccumulation behaviors between aquatic and terrestrial organisms. This study provides a new tool to accurately study the trophic transfer of contaminants in wetlands and terrestrial food webs with diverse species and complex feeding relationships.

Effect of mechanical ventilation under intubation on respiratory tract change of bacterial count and alteration of bacterial flora.

Background: The most common 'second strike' in mechanically ventilated patients is a pulmonary infection caused by the ease with which bacteria can invade and colonize the lungs due to mechanical ventilation. At the same time, metastasis of lower airway microbiota may have significant implications in developing intubation mechanical ventilation lung inflammation. Thus, we establish a rat model of tracheal intubation with mechanical ventilation and explore the effects of mechanical ventilation on lung injury and microbiological changes in rats. To provide a reference for preventing and treating bacterial flora imbalance and pulmonary infection injury caused by mechanical ventilation of tracheal intubation. Methods: Sprague-Dawley rats were randomly divided into Control, Mechanical ventilation under intubation (1, 3, 6 h) groups, and Spontaneously breathing under intubation (1, 3, 6 h). Lung histopathological injury scores were evaluated. 16SrDNA sequencing was performed to explore respiratory microbiota changes, especially, changes of bacterial count and alteration of bacterial flora. Results: Compared to groups C and SV, critical pathological changes in pulmonary lesions occurred in the MV group after 6 h (p < 0.05). The Alpha diversity and Beta diversity of lower respiratory tract microbiota in MV6, SV6, and C groups were statistically significant (p < 0.05). The main dominant bacterial phyla in the respiratory tract of rats were Proteobacteria, Firmicutes, Bacteroidetes, and Cyanobacteria. Acinetobacter radioresistens in group C was significant, Megaonas in group MV6 was significantly increased, and Parvibacter in group SV6 was significantly increased. Anaerobic, biofilm formation, and Gram-negative bacteria-related functional genes were altered during mechanical ventilation with endotracheal intubation. Conclusion: Mechanical ventilation under intubation may cause dysregulation of lower respiratory microbiota in rats.

Structural diversity and biological activities of indole-diterpenoids from Penicillium janthinellum by co-culture with Paecilomyces formosus.

Co-culturing the marine-derived fungi Penicillium janthinellium with Paecilomyces formosus led to the isolation of nine new indole-diterpenes, janthinellumines A-I (1-9), along with twelve known analogues (10-21). The chemical structures including their absolute configurations of them were assigned by the analysis of extensive spectroscopic data and calculated ECD and VCD methods. These indole-diterpenoids displayed extensive biological activities, including anti-influenza A virus, protein tyrosine phosphatase (PTP) inhibitory, and anti-Vibrio activities. Among them, the anti-influenza mechanism of compounds 1, 2, and 7 was further investigated using neuraminidase inhibitory assay, molecular docking, and reverse genetics methods, suggesting that 1, 2, and 7 could interact with Arg371 of the viral neuraminidase. The structure-activity relationship (SAR) of PTPs inhibitory activity for indole-diterpene derivatives (1, 2, 4, 5, 9-16, and 19-21) was also summarized.

Opportunities and challenges of trilateral South‒South cooperation for transforming development assistance for health: evidence from a DRC-UNICEF-China maternal, newborn, and child health project.

BACKGROUND: Trilateral South‒South cooperation is envisioned as an equal and empowering partnership model but still faces certain challenges. This study addresses whether and how trilateral South‒South cooperation can transform traditional development assistance for health (DAH) and explores the opportunities and challenges of trilateral South‒South cooperation for transforming future DAH, in the theme of "the emerging development partner's DAH transformation facilitated by a multilateral organization". METHODS: We evaluate a maternal, newborn, and child health (MNCH) project involving the Democratic Republic of Congo (DRC), the United Nations Children's Fund (UNICEF), and China (hereinafter referred to as the "DRC-UNICEF-China project"). We analyze data from project documents and seventeen semi-structured interviews using a pragmatic analytical framework based on the DAH program logic model and the OECD's trilateral cooperation framework. RESULTS: Evidence from the DRC-UNICEF-China MNCH project suggests that trilateral South‒South cooperation facilitated by a multilateral organization can provide transformative opportunities for emerging development partners' DAH to generate and deliver context-based, demand-oriented solutions, harmonize rules and procedures, institutionalize mutual learning and knowledge sharing, and increase the visibility of emerging development partners as sources for South‒South development experience transfer. However, the project revealed some challenges, including the neglect of key stakeholders in the complex governance structure, the high transaction costs needed to ensure transparency, and the harm local absence of the emerging development partner poses to long-term DAH engagement. CONCLUSIONS: This study echoes some of the findings in trilateral SSC literature that claim power structures and philanthropic, normative justification for health equity are often juxtaposed in trilateral SSC partnerships. The opportunities offered by the DRC-UNICEF-China project align with China's cognitive learning process for strengthening international engagement and global image building. However, challenges may arise as a result of complex governance structures and the entrustment of facilitating partners, which can threaten the effectiveness of trilateral cooperation. We call for strengthening the beneficiary partner's ownership at all levels, engaging the emerging development partner to better understand the beneficiary partner's local context(s) and needs, and ensuring available resources to support programmatic activities and long-term partnerships for the health and well-being of the beneficiaries.

Deep learning-assisted diagnosis of parotid gland tumors by using contrast-enhanced CT imaging.

OBJECTIVES: Imaging interpretation of the benignancy or malignancy of parotid gland tumors (PGTs) is a critical consideration prior to surgery in view of therapeutic and prognostic values of such discrimination. This study investigates the application of a deep learning-based method for preoperative stratification of PGTs. MATERIALS AND METHODS: Using the 3D DenseNet-121 architecture and a dataset consisting of 117 volumetric arterial-phase contrast-enhanced CT scans, we developed a binary classifier for PGT distinction and tested it. We compared the discriminative performance of the model on the test set to that of 12 junior and 12 senior head and neck clinicians. Besides, potential clinical utility of the model was evaluated by measuring changes in unassisted and model-assisted performance of junior clinicians. RESULTS: The model finally reached the sensitivity, specificity, PPV, NPV, F1-score of 0.955 (95% CI 0.751-0.998), 0.667 (95% CI 0.241-0.940), 0.913 (95% CI 0.705-0.985), 0.800 (95% CI 0.299-0.989) and 0.933, respectively, comparable to that of practicing clinicians. Furthermore, there were statistically significant increases in junior clinicians' specificity, PPV, NPV and F1-score in differentiating benign from malignant PGTs when unassisted and model-assisted performance of junior clinicians were compared. CONCLUSION: Our results provide evidence that deep learning-based method may offer assistance for PGT's binary distinction.

Advances in the differential diagnosis of transient hyperthyroidism in pregnancy and Graves' disease.

BACKGROUND: The occurrence of thyrotoxicosis during pregnancy is mainly attributed to gestational transient thyrotoxicosis (GTT) and Graves' disease (GD). It is important to distinguish between GTT and Graves' disease because the two diseases are treated very differently. However, a gold standard for the differential diagnosis of the two diseases is currently lacking, and the most common method of differentiation is based on past medical history and clinical presentation combined with thyroid-related antibodies. METHODS: A literature search of the electronic databases PubMed, Embase, Medline, Google Scholar, Cochrane Library, China Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Full Text Database and China Biomedical CD-ROM was performed. The search period ranged from journal inception until 2022. We used the following search terms in "All fields": {["thyroid" (common field) OR "thyroid" (subject line)] OR "hyperthyroidism" (common field)} AND {["pregnancy" (title) OR "pregnancy" (title)] AND "one over" (common field)} OR {["pregnancy" (common field) OR "pregnancy" (common field) OR "pregnancy" (subject line)] AND "Graves'" (common field)}. RESULTS: In recent years, some clinical studies at home and abroad have proposed other meaningful differential indicators, such as thyroid stimulating hormone, chorionic gonadotropin, thyroid hormone levels and thyroid ultrasound. CONCLUSION: The differential diagnostic significance of each of these indicators is summarised here with the goal of providing a better reference for the differential diagnosis of hyperthyroidism during pregnancy in clinical practice.

Scissor-like Au4Cu2 Cluster with Phosphorescent Mechanochromism and Thermochromism.

Reaction of [Au(tht)2](ClO4) (tht = tetrahydrothiophene), [Cu(CH3CN)4](ClO4), 3,6-di-tert-butyl-1,8-diethynyl-9H-carbazole (H3decz), and bis(2-diphenylphosphinophenyl)ether (POP) in the presence of triethylamine (NEt3) gave the cluster complex Au4Cu2(decz)2(POP)2 as yellow crystals. As revealed by X-ray crystallography, the Au4Cu2 cluster exhibits scissor-like structure sustained by two decz and two POP ligands and stabilized by Au-Cu and Au-Au interactions. The Au4Cu2 cluster shows bright yellow to orange photoluminescence upon irradiation at >300 nm, arising from 3[π (decz)→5d (Au)] 3LMCT (ligand-to-metal charge transfer) and 3[π→π* (decz)] 3IL (intraligand) triplet states as revealed by theoretical and computational studies. When it is mechanically ground, reversible phosphorescence conversion from yellow to red is observed owing to more compact molecular packing and thus stronger intermetallic interaction. Variable-temperature luminescence studies reveal that it displays distinct red-shifts of the emission whether the temperature is elevated or lowered from ambient temperature, suggestive of exceptional thermochromic phosphorescence characteristics.

Electrochemical Activation of Nitromethane to Construct Isoxazoline Aldoximes.

Activation of nitromethane to endow new reactivity is an interesting and meaningful but also challenging topic. Herein, we report an electrochemical activation of nitromethane to serve as both the heterocyclic skeleton and oxime sources for the construction of isoxazoline aldoximes. The isoxazoline aldoximes that are prepared by four steps with the reported strategy are synthesized in a single step from low-cost and readily available nitromethane and olefins with moderate to excellent yields under our electrochemical conditions. The reaction also takes advantage of high atom-economy and E-selectivity. Moreover, the mechanism is studied by control experiments, a kinetic isotope effect (KIE) study, cyclic voltammogram (CV) experiments, and density functional theory (DFT) calculations. The mechanistic results reveal that nitromethane may be activated under electrochemical conditions to deliver a 1,2,5-oxadiazole 2-oxide intermediate, which undergoes [3+2] cycloaddition with olefins to yield isoxazoline aldoximes.

Tubular epithelial cell-derived extracellular vesicles induce macrophage glycolysis by stabilizing HIF-1α in diabetic kidney disease.

BACKGROUND: Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. METHODS: Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. RESULTS: Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. CONCLUSION: Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria.

AQDS Activates Extracellular Synergistic Biodetoxification of Copper and Selenite via Altering the Coordination Environment of Outer-Membrane Proteins.

The biotransformation of heavy metals in the environment is usually affected by co-existing pollutants like selenium (Se), which may lower the ecotoxicity of heavy metals, but the underlying mechanisms remain unclear. Here, we shed light on the pathways of copper (Cu2+) and selenite (SeO32-) synergistic biodetoxification by Shewanella oneidensis MR-1 and illustrate how such processes are affected by anthraquinone-2,6-disulfonate (AQDS), an analogue of humic substances. We observed the formation of copper selenide nanoparticles (Cu2-xSe) from synergistic detoxification of Cu2+ and SeO32- in the periplasm. Interestingly, adding AQDS triggered a fundamental transition from periplasmic to extracellular reaction, enabling 14.7-fold faster Cu2+ biodetoxification (via mediated electron transfer) and 11.4-fold faster SeO32- detoxification (via direct electron transfer). This is mainly attributed to the slightly raised redox potential of the heme center of AQDS-coordinated outer-membrane proteins that accelerates electron efflux from the cells. Our work offers a fundamental understanding of the synergistic detoxification of heavy metals and Se in a complicated environmental matrix and unveils an unexpected role of AQDS beyond electron mediation, which may guide the development of more efficient environmental remediation and resource recovery biotechnologies.

A visual and reversible nanoprobe for rapid and on-site determination of hexavalent chromium and lysine based on dual-emission carbon quantum dots coupled with smartphone.

A straightforward, largely instrument-free, smartphone-based analytical strategy for hexavalent chromium and lysine (Lys) on-site detection via exploitation of dual-emission carbon quantum dots (DECQDs) has been demonstrated. DECQDs show dual-emission peaks at 439 and 630 nm with the excitation at 375 nm. As a dual-mode detection probe, the fluorescence and ultraviolet adsorption spectra of DECQDs vary with hexavalent chromium concentrations. Most importantly, Lys can restore the fluorescence of the hexavalent chromium added DECQD nanoprobe and change the color of the probe under natural light. At the same time, based on the participation of smartphones, the prepared DECQD probes favor the establishment of visual smart sensors that can also be used for the in-situ detection of targets. The on-site quantitative analysis exhibited a linear range of 5.3-320 µM with a detection limit of 1.6 µM towards Cr(VI) and the differentiation of Lys variation from 1 to 75 mM with a detection limit of 0.3 mM. The probe has been applied for the first time to enable vision-based colorimetric in complex samples such as water, milk and egg. The recoveries of Cr(VI) and Lys in real samples were between 90 and 104%, and the relative standard deviation (RSD) was as low as 0.4%. This work offers new perspectives for fundamental understanding and new design of functional luminescent materials that are applicable for food-safety and rapid and intelligent inspection. A straightforward, large instrument-free, smartphone-based analytical strategy with dual-emission carbon quantum dots was developed for hexavalent chromium and Lys on-site detection via fluorescent and colorimetric twofold readout measure.

MdPP2C24/37, Protein Phosphatase Type 2Cs from Apple, Interact with MdPYL2/12 to Negatively Regulate ABA Signaling in Transgenic Arabidopsis.

The phytohormone abscisic acid (ABA) plays an important role in the ability of plants to cope with drought stress. As core members of the ABA signaling pathway, protein phosphatase type 2Cs (PP2Cs) have been reported in many species. However, the functions of MdPP2Cs in apple (Malus domestica) are unclear. In this study, we identified two PP2C-encoding genes, MdPP2C24/37, with conserved PP2C catalytic domains, using sequence alignment. The nucleus-located MdPP2C24/37 genes were induced by ABA or mannitol in apple. Genetic analysis revealed that overexpression of MdPP2C24/37 in Arabidopsis thaliana led to plant insensitivity to ABA or mannitol treatment, in terms of inhibiting seed germination and overall seedling establishment. The expression of stress marker genes was upregulated in MdPP2C24/37 transgenic lines. At the same time, MdPP2C24/37 transgenic lines displayed inhibited ABA-mediated stomatal closure, which led to higher water loss rates. Moreover, when exposed to drought stress, chlorophyll levels decreased and MDA and H2O2 levels accumulated in the MdPP2C24/37 transgenic lines. Further, MdPP2C24/37 interacted with MdPYL2/12 in vitro and vivo. The results indicate that MdPP2C24/37 act as negative regulators in response to ABA-mediated drought resistance.