Development of novel lysosome-related signatures and their potential target drugs based on bulk RNA-seq and scRNA-seq for diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcers (DFU) is the most serious complication of diabetes mellitus, which has become a global health problem due to its high morbidity and disability rates and the poor efficacy of conventional treatments. Thus, it is urgent to identify novel molecular targets to improve the prognosis and reduce disability rate in DFU patients. RESULTS: In the present study, bulk RNA-seq and scRNA-seq associated with DFU were downloaded from the GEO database. We identified 1393 DFU-related DEGs by differential analysis and WGCNA analysis together, and GO/KEGG analysis showed that these genes were associated with lysosomal and immune/inflammatory responses. Immediately thereafter, we identified CLU, RABGEF1 and ENPEP as DLGs for DFU using three machine learning algorithms (Randomforest, SVM-RFE and LASSO) and validated their diagnostic performance in a validation cohort independent of this study. Subsequently, we constructed a novel artificial neural network model for molecular diagnosis of DFU based on DLGs, and the diagnostic performance in the training and validation cohorts was sound. In single-cell sequencing, the heterogeneous expression of DLGs also provided favorable evidence for them to be potential diagnostic targets. In addition, the results of immune infiltration analysis showed that the abundance of mainstream immune cells, including B/T cells, was down-regulated in DFUs and significantly correlated with the expression of DLGs. Finally, we found latamoxef, parthenolide, meclofenoxate, and lomustine to be promising anti-DFU drugs by targeting DLGs. CONCLUSIONS: CLU, RABGEF1 and ENPEP can be used as novel lysosomal molecular signatures of DFU, and by targeting them, latamoxef, parthenolide, meclofenoxate and lomustine were identified as promising anti-DFU drugs. The present study provides new perspectives for the diagnosis and treatment of DFU and for improving the prognosis of DFU patients.

MYB2 and MYB108 regulate lateral root development by interacting with LBD29 in Arabidopsis thaliana.

AUXIN RESPONSE FACTOR 7 (ARF7)-mediated auxin signaling plays a key role in lateral root (LR) development by regulating downstream LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor genes, including LBD16, LBD18, and LBD29. LBD proteins are believed to regulate the transcription of downstream genes as homodimers or heterodimers. However, whether LBD29 forms dimers with other proteins to regulate LR development remains unknown. Here, we determined that the Arabidopsis thaliana (L.) Heynh. MYB transcription factors MYB2 and MYB108 interact with LBD29 and regulate auxin-induced LR development. Both MYB2 and MYB108 were induced by auxin in an ARF7-dependent manner. Disruption of MYB2 by fusion with an SRDX domain severely affected auxin-induced LR formation and the ability of LBD29 to induce LR development. By contrast, overexpression of MYB2 or MYB108 resulted in greater LR numbers, except in the lbd29 mutant background. These findings underscore the interdependence and importance of MYB2, MYB108, and LBD29 in regulating LR development. In addition, MYB2-LBD29 and MYB108-LBD29 complexes promoted the expression of CUTICLE DESTRUCTING FACTOR 1 (CDEF1), a member of the GDSL (Gly-Asp-Ser-Leu) lipase/esterase family involved in LR development. In summary, this study identified MYB2-LBD29 and MYB108-LBD29 regulatory modules that act downstream of ARF7 and intricately control auxin-mediated LR development.

Enhancing storage and gastroprotective viability of Lactiplantibacillus plantarum encapsulated by sodium caseinate-inulin-soy protein isolates composites carried within carboxymethyl cellulose hydrogel.

Probiotics are subjected to various edible coatings, especially proteins and polysaccharides, which serve as the predominant wall materials, with ultrasound, a sustainable green technology. Herein, sodium caseinate, inulin, and soy protein isolate composites were produced using multi-frequency ultrasound and utilized to encapsulateLactiplantibacillus plantarumto enhance its storage, thermal, and gastrointestinal viability. The physicochemical analyses revealed that the composites with 5 % soy protein isolate treated with ultrasound at 50 kHz exhibited enough repulsion forces to maintain stability, pH resistance, and the ability to encapsulate larger particles and possessed the highest encapsulation efficiency (95.95 %). The structural analyses showed changes in the composite structure at CC, CH, CO, and amino acid residual levels. Rheology, texture, and water-holding capacity demonstrated the production of soft hydrogels with mild chewing and gummy properties, carried the microcapsules without coagulation or sedimentation. Moreover, the viability attributes ofL. plantarumevinced superior encapsulation, protecting them for at least eight weeks and against heat (63 °C), reactive oxidative species (H2O2), and GI conditions.

Microwave-Assisted Pyrolysis-A New Way for the Sustainable Recycling and Upgrading of Plastic and Biomass: A Review.

The efficient utilization of organic solid waste resources can help reducing the consumption of conventional fossil fuels, mitigating environmental pollution, and achieving green sustainable development. Due to its dual nature of being both a resource and a source of pollution, it is crucial to implement suitable recycling technologies throughout the recycling and upgrading processes for plastics and biomass, which are organic solid wastes with complex mixture of components. The conventional pyrolysis and hydropyrolysis were summarized for recycling plastics and biomass into high-value fuels, chemicals, and materials. To enhance reaction efficiency and improve product selectivity, microwave-assisted pyrolysis was introduced to the upgrading of plastics and biomass through efficient energy supply especially with the aid of catalysts and microwave absorbers. This review provides a detail summary of microwave-assisted pyrolysis for plastics and biomass from the technical, applied, and mechanistic perspectives. Based on the recent technological advances, the future directions for the development of microwave-assisted pyrolysis technologies are predicted.

Minimal residual disease monitoring in childhood Philadelphia chromosome-positive acute lymphoblastic leukemia: prognostic significance and correlation between multiparameter flow cytometry and real-time quantitative polymerase chain reaction

Not available.

Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

ERSegDiff: a diffusion-based model for edge reshaping in medical image segmentation.

Medical image segmentation is a crucial field of computer vision. Obtaining correct pathological areas can help clinicians analyze patient conditions more precisely. We have observed that both CNN-based and attention-based neural networks often produce rough segmentation results around the edges of the regions of interest. This significantly impacts the accuracy of obtaining the pathological areas. Without altering the original data and model architecture, further refining the initial segmentation outcomes can effectively address this issue and lead to more satisfactory results. Recently, diffusion models have demonstrated outstanding results in image generation, showcasing their powerful ability to model distributions. We believe that this ability can greatly enhance the accuracy of the reshaping results. This research proposes ERSegDiff, a neural network based on the diffusion model for reshaping segmentation borders. The diffusion model is trained to fit the distribution of the target edge area and is then used to modify the segmentation edge to produce more accurate segmentation results. By incorporating prior knowledge into the diffusion model, we can help it more accurately simulate the edge probability distribution of the samples. Moreover, we introduce the edge concern module, which leverages attention mechanisms to produce feature weights and further refine the segmentation outcomes. To validate our approach, we employed the COVID-19 and ISIC-2018 datasets for lung segmentation and skin cancer segmentation tasks, respectively. Compared with the baseline model, ERSegDiff improved the dice score by 3%-4% and 2%-4%, respectively, and achieved state-of-the-art scores compared to several mainstream neural networks, such as swinUNETR.

Fluorinated Lipid Nanoparticles for Enhancing mRNA Delivery Efficiency.

Lipid nanoparticles (LNPs), a nonviral nucleic acid delivery system, have shown vast potential for vaccine development and disease treatment. LNPs assist mRNA to cross physiological barriers such as cell membranes and endosomes/lysosomes, promoting the intracellular presentation of mRNA. However, the endosome escape efficiency and biosafety of currently commercialized LNPs are still unsatisfactory, resulting in underutilization of mRNA. Herein, we report that fluorinated modification of the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-2000 (PEG-DSPE), termed as FPD, in the LNPs can improve the delivery efficiency of mRNA. FPD accounts for only 1.5% of lipids in LNPs but could mediate a 5-fold and nearly 2-fold enhancement of mRNA expression efficiency in B16F10 tumor cells and primary dendritic cells, respectively. Mechanism studies reveal that FPD promotes the cellular internalization of LNPs as well as endosome escape. In vivo studies substantiate that FPD can augment overall mRNA expression at least 3-fold, either by intravenous or intraperitoneal injection, compared to LNPs prepared with nonfluorinated PEG-lipids at a relatively low mRNA dose. Besides, with the introduction of FPD, mRNA expression in the spleen augmented compared to that of the DMG-PEG commercial formulations. Benefiting from a prudent dosage of fluorine, the fluorinated LNPs display favorable biosafety profiles at cellular and zoological levels.

Effective dose of propofol combined with intravenous esketamine for smooth flexible laryngeal mask airway insertion in two distinct age groups of preschool children.

BACKGROUND: There is limited research on the combined use of propofol and esketamine for anesthesia induction during flexible laryngeal mask airway (FLMA) in pediatric patients, and the effective dosage of propofol for FLMA smooth insertion remains unclear. We explored the effective dose of propofol combined with intravenous esketamine for the smooth insertion of FLMA in two distinct age groups of preschool children. METHODS: This is a prospective, observer-blind, interventional clinical study. Based on age, preschool children scheduled for elective surgery were divided into group A (aged 1-3 years) and group B (aged 3-6 years). Anesthesia induction was started with intravenous administration of esketamine (1.0 mg.kg- 1) followed by propofol administration. The FLMA was inserted 2 min after propofol administration at the target dose. The initial dose of propofol in group A and group B was 3.0 mg.kg- 1 and 2.5 mg.kg- 1, respectively. The target dose of propofol was determined with Dixon's up-and-down method, and the dosing interval of propofol was 0.5 mg.kg- 1. If there was smooth insertion of FLMA in the previous patient, the target dose of propofol for the next patient was reduced by 0.5 mg.kg- 1; otherwise, it was increased by 0.5 mg.kg- 1. The median 50% effective dose (ED50) for propofol was estimated using Dixon's up-and-down method and Probit analysis, while the 95% effective dose (ED95) was estimated through Probit analysis. Vital signs and adverse events during induction were recorded. RESULTS: Each group included 24 pediatric patients. Using Dixon's up-and-down method, the ED50 of propofol combined with esketamine for smooth insertion of FLMA in group A was 2.67 mg.kg- 1 (95%CI: 1.63-3.72), which was higher than that in group B (2.10 mg. kg- 1, 95%CI: 1.36-2.84) (p = 0.04). Using Probit analysis, the ED50 of propofol was calculated as 2.44 (95% CI: 1.02-3.15) mg.kg- 1 in group A and 1.93 (95% CI: 1.39-2.32) mg.kg- 1 in group B. The ED95 of propofol was 3.72 (95%CI: 3.07-15.18) mg.kg- 1 in group A and 2.74 (95%CI: 2.34-5.54) mg.kg- 1 in group B. In Group B, one pediatric patient experienced laryngospasm. CONCLUSION: The effective dose of propofol when combined with intravenous esketamine for smooth insertion of FLMA in children aged 1-3 years is 2.67 mg.kg- 1, which is higher than that in children aged 3-6 years (2.10 mg. kg- 1). TRIAL REGISTRATION: Chinese Clinical Trial Registry Center (Registration Number: ChiCTR2100044317; Registration Date: 2021/03/16).

The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs.

Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.

A PilZ domain protein interacts with the transcriptional regulator HinK to regulate type VI secretion system in Pseudomonas aeruginosa.

Type VI secretion systems (T6SS) are bacterial macromolecular complexes that secrete effectors into target cells or the extracellular environment, leading to the demise of adjacent cells and providing a survival advantage. Although studies have shown that the T6SS in Pseudomonas aeruginosa is regulated by the Quorum Sensing system and second messenger c-di-GMP, the underlying molecular mechanism remains largely unknown. In this study, we discovered that the c-di-GMP-binding adaptor protein PA0012 has a repressive effect on the expression of the T6SS HSI-I genes in P. aeruginosa PAO1. To probe the mechanism by which PA0012 (renamed TssZ, Type Six Secretion System -associated PilZ protein) regulates the expression of HSI-I genes, we conducted yeast two-hybrid screening and identified HinK, a LasR-type transcriptional regulator, as the binding partner of TssZ. The protein-protein interaction between HinK and TssZ was confirmed through co-immunoprecipitation assays. Further analysis suggested that the HinK-TssZ interaction was weakened at high c-di-GMP concentrations, contrary to the current paradigm wherein c-di-GMP enhances the interaction between PilZ proteins and their partners. Electrophoretic mobility shift assays revealed that the non-c-di-GMP-binding mutant TssZR5A/R9A interacts directly with HinK and prevents it from binding to the promoter of the quorum-sensing regulator pqsR. The functional connection between TssZ and HinK is further supported by observations that TssZ and HinK impact the swarming motility, pyocyanin production, and T6SS-mediated bacterial killing activity of P. aeruginosa in a PqsR-dependent manner. Together, these results unveil a novel regulatory mechanism wherein TssZ functions as an inhibitor that interacts with HinK to control gene expression.

FlgI Is a Sec-Dependent Effector of Candidatus Liberibacter asiaticus That Can Be Blocked by Small Molecules Identified Using a Yeast Screen.

Huanglongbing (HLB) is one of the most devastating diseases of citrus worldwide. The phloem-restricted bacterium Candidatus Liberibacter asiaticus (CLas) is considered to be the main pathogen responsible for HLB. There is currently no effective practical strategy for the control of HLB. Our understanding of how pathogens cause HLB is limited because CLas has not been artificially cultured. In this study, 15 potential virulence factors were predicted from the proteome of CLas through DeepVF and PHI-base searches. One among them, FlgI, was found to inhibit yeast growth when expressed in Saccharomyces cerevisiae. The expression of the signal peptide of FlgI fused with PhoA in Escherichia coli resulted in the discovery that FlgI was a novel Sec-dependent secretory protein. We further found that the carboxyl-terminal HA-tagged FlgI was secreted via outer membrane vesicles in Sinorhizobium meliloti. Fluoresence localization of transient expression FlgI-GFP in Nicotiana benthamiana revealed that FlgI is mainly localized in the cytoplasm, cell periphery, and nuclear periphery of tobacco cells. In addition, our experimental results suggest that FlgI has a strong ability to induce callose deposition and cell necrosis in N. benthamiana. Finally, by screening a large library of compounds in a high-throughput format, we found that cyclosporin A restored the growth of FlgI-expressing yeast. These results confirm that FlgI is a novel Sec-dependent effector, enriching our understanding of CLas pathogenicity and helping to develop new and more effective strategies to manage HLB.

Tenapanor in Chinese ESRD patients with hyperphosphatemia on haemodialysis: a randomised, phase 3 trial.

Background: The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD). Methods: This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug. Results: Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment (n = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo (n = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, P < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor. Conclusions: Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.

[Matrix solid-phase dispersion extraction of organophosphorus flame retardants in soil based on response surface methodology].

Organophosphorus flame retardants (OPFRs) are widely used in commercial products owing to their exceptional flame-retarding and plasticizing properties. However, OPFRs are also well recognized as emerging persistent organic pollutants (POPs) because of their environmental persistence, biological concentration, and potential toxicity. Thus, the accurate detection of OPFRs in environmental media is critical for analyzing their fate, transport, and ecological risk. However, very few OPFR detection methods are currently available, and the types of OPFRs detected may vary from site to site. In this study, matrix solid-phase dispersion extraction (MSPD), a simple, rapid, and versatile technique for preparing solid, semisolid, liquid, and viscous samples, was combined for the first time with gas chromatography-tandem mass spectrometry (GC-MS/MS) to analyze 10 OPFRs in soil, namely, tripropyl phosphate (TPrP), tri-n-butyl phosphate (TnBP), tri-iso-butyl phosphate (TiBP), tris(2-chloroisopropyl) phosphate (TCIPP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP), triphenylphosphine oxide (TPPO), and trimethylphenyl phosphate (TCP). The GC-MS/MS system was equipped with a Bruker-5MS capillary column coupled with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode. Prior to detection, a mixed standard solution was fortified with 10 ng of13C-PCB208 as an internal standard. The optimal conditions under which MSPD could achieve high selectivity for OPFRs were determined. In addition, single-factor analysis was used to examine the influence of the sorbent (i. e., C18, PSA, Florisil, GCB, and multiwalled carbon nanotubes (MWCNTs)) as well as the dosage, type, and volume of the eluent on the extraction efficiency of the method for the 10 OPFRs. When GCB and ethyl acetate were used as the adsorbent and solvent, respectively, during elution, high extraction recoveries for the OPFRs were achieved. Optimization via response surface methodology (RSM) was adopted to further analyze the impact of three key factors, namely, the adsorbent dosage, eluent volume, and grinding time, as well as their interactions, on OPFR recoveries. Under the optimal conditions of 0.3 g of GCB as the adsorbent, 10 mL of ethyl acetate as the eluent, and 5 min of grinding time, the relative average recovery of the OPFRs was 87.5%. Furthermore, the 10 OPFRs showed good linear relationships under five concentration gradients, with correlation coefficients greater than 0.998. The limits of detection (LODs) and quantification (LOQs) were calculated as signal-to-noise ratios (S/N) of 3 and 10, respectively, and found to be in the ranges of 0.006-0.161 and 0.020-0.531 ng/g, respectively. The performance of the proposed method was verified by determining the recoveries and relative standard deviations (RSDs) of the OPFRs in soils spiked at low, medium, and high levels (10, 20, and 100 ng/g, respectively). The recoveries of the OPFRs ranged from 70.4% to 115.4%, with RSDs ranging from 0.7% to 6.7%. Compared with the conventional accelerated solvent extraction (ASE) method, MSPD presents higher efficiency, simpler operation, and less solvent requirements. The developed method was applied to determine OPFRs in soil samples collected from different sites in Suzhou, including an electronics factory, an auto-repair factory, a paddy field, and a school field. The results revealed that the contents of OPFRs in the soils from the electronics and auto-repair factories were significantly higher than those in the soils from the paddy and school fields. The main pollutants in the soil samples collected from the electronics and auto-repair factories were TCIPP, TPPO, TCEP, and TDCPP. Moreover, the contents of these compounds were 5.30, 4.44, 4.54, and 4.20 ng/g, in soils from the electronics factory and 2.70, 3.93, 7.60, and 5.04 ng/g, in soils from the auto-repair factory. To the best of our knowledge, this study is the first to determine high concentrations of TPPO in industrial soils. Thus, the combination of MSPD and GC-MS/MS adopted in this study can provide useful insights into the detection of the 10 OPFRs in soil.

A dual-emitting fluoroprobe fabricated by aloe leaf-based N-doped carbon quantum dots and copper nanoclusters for nitenpyram detection in waters by virtue of inner filter effect and static quenching principles.

Fluorescence sensing technique has been used in environmental analysis due to its simplicity, low cost, and visualization. Although the fruit pulp-based biomass carbon quantum dots (CQDs) have excellent luminescent properties, aloe leaves possess the superiority of being easily accessible in all seasons compared to fruit pulp. Thus, we fabricated Aloe carazo leaf-based nitrogen doping-CQDs (N-CQDs) using a facile hydrothermal approach, which emitted bright blue fluorescence with a quantum yield of 21.4 %. By comparison, the glutathione-encapsulated copper nanoclusters (GSH-CuNCs) displayed strong red fluorescence. A blue/red dual emission based on the N-CQDs/CuNCs mixture was established for nitenpyram detection. At the 350-nm excitation, the N-CQD/CuNCs system produced dual-wavelength emitting peaks at 440 and 660 nm, respectively. Moreover, when nitenpyram was introduced into the system, the fluorescence intensities (FIs) of N-CQDs significantly decreased, whereas the FIs of GSH-CuNCs varied slightly; simultaneously, the solution color changed from bright blue to dark red. Both the spectral overlapping between nitenpyram's UV-Vis absorption and N-CQDs' excitation and almost unchanged fluorescence lifetimes indicated the occurrence of inner-filtering effect (IFE) in the dual-emitting fluoroprobe. In addition, the Stern-Volmer constant (Ksv = 6.92 × 103 M-1), temperature effect, as well as UV-Vis absorption of N-CQD/CuNCs before and after the addition of nitenpyram corroborated the static-quenching behavior. Consequently, the fluorescence-quenching of N-CQDs by nitenpyram was attributable to the joint IFE and static-quenching principles. A good linearity existed between the F660/F440 values and nitenpyram concentrations (0.5-200 µM) with a method detection limit of 0.15 µM. The dual-emitting fluoroprobe provided the satisfactory recoveries (95.0%-107.0 %) for nitenpyram detection in real-world waters, which were comparable with the results of traditional liquid chromatography coupled to tandem mass spectrometry method. Owing to its simple operations, low-cost, and adaptability for on-site outdoor monitoring, the newly developed dual-emitting fluoroprobe possesses great potential applications in routine monitoring of nitenpyram under field conditions.

Thermally activated persulfate (TAP)-enhanced tris(2-chloroethyl) phosphate removal in real-world waters based on a response-surface approach as well as toxicological evaluation on its degradation products.

As a typical organophosphorus flame retardant, tris(2-chloroethyl) phosphate (TCEP) is refractory in aqueous environment. The application of TAP is a promising method for removing pollutants. Herein, the removal of TCEP using TAP was rigorously investigated, and the effects of some key variables were optimized by the one-factor-at-a-time approach. To further evaluate the interactions among variables, the response surface methodology (RSM) based on central composite design was employed. Under optimized conditions (pH 5, [PS]0: [TCEP]0 = 500:1), the maximum removal efficiency (RE) of TCEP reached up to 90.6%. In real-world waters, the RE of TCEP spanned the range of 56%- 65% in river water, pond water, lake water and sanitary sewage. The low-concentration Cl- (0.1 mM) promoted TCEP degradation, but the contrary case occurred when the high-concentration Cl-, NO3-, CO32-, HCO3-, HPO42-, H2PO4-, NH4+ and humic acid were present owing to their prominently quenching effects on SO4•-. Both EPR and scavenger experiments revealed that the main radicals in the TAP system were SO4•- and •OH, in which SO4•- played the most crucial role in TCEP degradation. GC-MS/MS analysis disclosed that two degradation products appeared, sourcing from the replacement, oxidation, hydroxylation and water-molecule elimination reactions. The other two products were inferred from the comprehensive literature. As for acute toxicity to fish, daphnid and green algae, product A displayed the slightly higher toxicity, whereas other three products exhibited the declining toxicity as compared to their parent molecule. These findings offer a theoretical/practical reference for high-efficiency removal of TCEP and its ecotoxicological risk evaluation.

Hydrophobization of Ribonucleic Acids for Facile Systemic Delivery and Multifaceted Cancer Immunotherapy.

Ribonucleic acids (RNAs) enable disease-related gene inhibition, expression, and editing and represent promising therapeutics in various diseases. The efficacy of RNA relies heavily on the presence of a secure and effective delivery system. Herein, we found that RNA could be hydrophobized by cationic lipid and ionizable lipid and conveniently coassemble with amphiphilic polymer to achieve micelle-like nanoparticles (MNP). The results of the study indicate that MNP exhibits a high level of efficiency in delivering RNA. Besides, the MNP encapsulating siRNA that targets CD47 and PD-L1 remarkably blocked these immune checkpoints in a melanoma tumor model and elicited a robust immune response. Moreover, the MNP encapsulating the mRNA of OVA achieved antigen translation and presentation, leading to an effective antitumor immunoprophylaxis outcome against OVA-expressing melanoma model. Our findings suggest that RNA hydrophobization could serve as a viable approach for delivering RNA, thereby facilitating the exploration of RNA therapy in disease treatment.

Protein post-translational modifications in auxin signaling.

Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating protein stability, activity, subcellular localization, and binding with cofactors. Such modifications remarkably increase the variety and complexity of proteomes, which are essential for regulating numerous cellular and physiological processes. The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development. Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations. Thus, a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes. This review discusses the progress of protein ubiquitination, phosphorylation, histone acetylation and methylation, SUMOylation, and S-nitrosylation in the regulation of auxin signaling.

Activating Tumor-Selective Liquid Metal Nanomedicine through Galvanic Replacement.

Advanced chemotherapeutic strategies including prodrug and nanocatalytic medicine have significantly advanced tumor-selective theranostics, but delicate prodrug screening, tedious synthesis, low degradability/biocompatibility of inorganic components, and unsatisfied reaction activity complicate treatment efficacies. Here, the intrinsic anticancer bioactivity of liquid metal nanodroplets (LMNDs) is explored through galvanic replacement. By utilizing a mechano-degradable ligand, the resultant size of the aqueous LMND is unexpectedly controlled as small as ≈20 nm (LMND20). It is demonstrated that LMND20 presents excellent tumor penetration and biocompatibility and activates tumor-selective carrier-to-drug conversion, synchronously depleting Cu2+ ions and producing Ga3+ ions through galvanic replacement. Together with abundant generation of reactive oxygen species, multiple anticancer pathways lead to selective apoptosis and anti-angiogenesis of breast cancer cells. Compared to the preclinical/clinical anticancer drugs of tetrathiomolybdate and Ga(NO3 )3 , LMND20 administration significantly improves the therapeutic efficacy and survival in a BCap-37 xenograft mouse model, yet without obvious side effects.

Ginsenoside F2-Mediated Intestinal Microbiota and Its Metabolite Propionic Acid Positively Impact the Gut-Skin Axis in Atopic Dermatitis Mice.

Atopic dermatitis (AD) is a complex inflammatory skin disease induced by multiple factors. AD can also cause intestinal inflammation and disorders of the gut microbiota. Ginseng is a kind of edible and medicinal plant; its main active components are ginsenosides. Ginsenosides have a variety of anti-inflammatory effects and regulate the gut microbiota; however, their role in AD and the underlying mechanisms are unclear. In this study, we found that intragastric administration of ginsenoside F2 improved AD-like skin symptoms and reduced inflammatory cell infiltration, serum immunoglobulin E levels, and mRNA expression of inflammatory cytokines in AD mice. 16s rRNA sequencing analysis showed that ginsenoside F2 altered the intestinal microbiota structure and enriched the short-chain fatty acid-producing microbiota in AD mice. Metabolomic analysis revealed that ginsenoside F2 significantly increased the propionic acid (Pa) content of feces and serum in AD mice, which was positively correlated with significant enrichment of Parabacteroides goldsteinii and Lactobacillus plantarum in the intestines. Pa inhibits inflammatory responses in the gut and skin of AD mice through the G-protein-coupled receptor43/NF-κB pathway, thereby improving skin AD symptoms. These results revealed, for the first time, the mechanism by which ginsenoside F2 improves AD through the Pa (a metabolite of intestinal microbiota)-gut-skin axis.