Dynamics and thermochemistry of the negatively charged clusters in a 2-hydroxyethylhydrazinium nitrate ionic liquid system.

The formation and fragmentation of negatively charged 2-hydroxyethylhydrazinium nitrate ([HOCH2CH2NH2NH2]+NO3-, HEHN) ionic liquid clusters were examined using a guided-ion beam tandem mass spectrometer furnished with collision-induced dissociation of selected ions with Xe atoms. Measurements included the compositions of cluster ions formed in the ionization source, and the dissociation products, cross sections, and 0 K threshold energies for individually selected cluster ions. To identify the structures of the main cluster ion series [(HEHN)n(HNO3)0-1NO3]- formed, molecular dynamics simulations were employed to create initial geometry guesses, followed by optimization at the ωB97XD/6-31+G(d,p) level of theory, from which global minimum structures were identified for reaction thermodynamics analyses. A comparison was made between the cluster formation and fragmentation in the negatively charged 2-hydroxyethylhydrazinium nitrate with those in the positive mode (reported by W. Zhou et al., Phys. Chem. Chem. Phys., 2023, 25, 17370). In both modes, the cluster ions were predominantly composed of m/z below 350; loss of a neutral 2-hydroxyethylhydrazinium nitrate ion pair represents the most important cluster fragmentation pathway, followed by intra-ion pair proton transfer-mediated 2-hydroxyethylhydrazine and HNO3 elimination; and all clusters started to dissociate at threshold energies less than 1.5 eV. The overwhelming similarities in the formation and fragmentation chemistry of positively vs. negatively charged 2-hydroxyethylhydrazinium nitrate clusters may be attributed to their inherent ionic nature and high electric conductivities.

G-quadruplex-Based Artificial Transmembrane Channels Induce Cancer Cell Apoptosis by Perturbing Potassium Ion Homeostasis.

Transmembrane ion transport modality has received a widespread attention due to its apoptotic activation toward anticancer cell activities. In this study, G-quadruplex-based potassium-specific transmembrane channels have been developed to facilitate the intracellular K+ efflux, which perturbs the cellular ion homeostasis thereby inducing cancer cell apoptosis. Cholesterol-tag, a lipophilic anchor moiety, serves as a rudiment for the G-quadruplex immobilization onto the membrane, while G-quadruplex channel structure as a transport module permits ion binding and migration along the channels. A c-Myc sequence tagged with two-cholesterol is designed as a representative lipophilic G-quadruplex, which forms intramolecular parallel G-quadruplex with three stacks of G-quartets (Ch2-Para3). Fluorescence transport assay demonstrates Ch2-Para3 a high transport activity (EC50 = 10.9 × 10-6 m) and an ion selectivity (K+/Na+ selectivity ratio of 84). Ch2-Para3 mediated K+ efflux in cancer cells is revealed to purge cancer cells through K+ efflux-mediated cell apoptosis, which is confirmed by monitoring the changes in membrane potential of mitochondria, leakage of cytochrome c, reactive oxygen species yield, as well as activation of a family of caspases. The lipophilic G-quadruplex exhibits obvious antitumor activity in vivo without systemic toxicity. This study provides a functional scheme aimed at generating DNA-based selective artificial membrane channels for the purpose of regulating cellular processes and inducing cell apoptosis, which shows a great promising for anticancer therapy in the future.

Determination of the effective dose of remimazolam combined with sufentanil for inhibiting body movement during surgical abortion: An up-and-down sequential allocation trial.

BACKGROUND: Remimazolam, a recently developed anesthetic characterized by its rapid and ultra-short-acting properties, exhibits pharmacological attributes that make it potentially suitable for painless surgical abortion procedures. The objective of this study was to determine the effective dose of remimazolam when administered in combination with sufentanil, with the intention of inhibiting body movement during surgical abortion. Additionally, a secondary objective was to assess the recovery profile from general anesthesia. METHODS: The study enrolled a total of 25 healthy women aged 20 to 40, with a body mass index between 18 and 28 kg/m2, in their first trimester of pregnancy (up to 12 weeks), and American Society of Anesthesiologists status I and II. Anesthesia induction was initiated by administering sufentanil at a dose of 0.1 µg/kg. The modified Dixon up-and-down method was employed to determine the induction dose of remimazolam for each patient. RESULTS: The 50% and 95% effective dose of remimazolam for inhibitory effects of body movement was estimated using centered isotonic regression to be 0.145 mg/kg (95% CI: 0.115, 0.207), and 0.242 mg/kg (95% CI: 0.232, 0.620), respectively. Five out of 25 (20%) experienced hiccups, with 1 patient having persistent hiccups until the end of the surgery. The mean time to first eye-opening was 51.4 ±â€…20.5 seconds, and the time to obey verbal command was 54.5 ±â€…20.6 seconds. Upon arrival at the postanesthesia care unit, 95.7% of the patients achieved a Modified Aldrete score ≥ 9. CONCLUSIONS: The 50% and 95% effective dose of remimazolam for inhibiting body movement during surgical abortion when used in combination with 0.1 µg/kg of sufentanil were 0.145 mg/kg and 0.242 mg/kg, respectively.

n-Bu4NI/K2S2O8-MEDIATED C-N COUPLING BETWEEN ALDEHYDES AND AMIDES.

n-Bu4NI/K2S2O8 mediated C-N coupling between aldehydes and amides is reported. A strong electronic effect is observed on the aromatic aldehyde substrates. The transformylation from aldehyde to amide takes place exclusively when an aromatic aldehyde bears electron-donating groups at either the ortho or para position of the formyl group, while the cross-dehydrogenative coupling dominates in the absence of these groups. Both the density functional theory (DFT) thermochemistry calculations and experimental data support the proposed single electron transfer mechanism with the formation of an acyl radical intermediate in the cross-dehydrogenative coupling. The n-Bu4NI/K2S2O8 mediated oxidative cyclization between 2-aminobenzamide and aldehydes is also reported, with four quinazolin-4(3H)-ones prepared in 65-99% yields.

Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications.

Erythrocytes, also known as red blood cells (RBCs), have garnered considerable attention as potential carriers for drug delivery, owing to their inherent properties such as biocompatibility, biodegradability, and prolonged circulation half-life. This paper presents a comprehensive overview of the role of erythrocytes in drug delivery, elucidating recent advancements in delivering a diverse array of therapeutic agents, including small molecules, nucleic acids, antibodies, protein enzymes, and nanoparticles. Two primary strategies for encapsulating drugs within erythrocytes are systematically discussed: internal loading and surface loading. Each strategy offers distinct advantages in terms of drug stability and release kinetics. Notably, the utilization of erythrocyte membrane camouflaged nanocarriers holds promise for enhancing the biocompatibility of conventional nanoparticles and facilitating targeted drug delivery. Furthermore, the broad spectrum of biomedical applications of erythrocyte-based drug delivery systems are examined, ranging from cancer treatment to diabetes management, thrombosis prevention, and immunotherapy. This review provides a comprehensive evaluation of current technologies in erythrocyte-loaded drug delivery, highlighting the strengths, weaknesses, and future directions for advancing therapeutic interventions in various disease contexts.

CuInS2/Red Phosphorus Nanosheet Interleaved Heterostructures with Improved Interfacial Charge Transfer for Photoelectrochemical Aptasensing.

Accelerating the migration of interfacial carriers in heterojunctions is crucial for achieving highly sensitive photoelectrochemical (PEC) sensing. In this study, we developed three-dimensional (3D)/two-dimensional (2D) CuInS2/red phosphorus nanosheet (CuInS2/RP NS) n-n heterojunction functional materials with enhanced interfacial charge transfer capabilities for PEC sensing. The 3D CuInS2 serves as a conductive layer, providing excellent electronic conductivity and superior electron absorption and transport properties. In contrast, the ultrathin RP NS acts as a transport layer that enhances carrier mobility. The 3D/2D heterojunction ensures a large interface contact surface, shortening the carrier transport distance. A well-aligned band position generates a substantial built-in electric field, providing a significant driving force for efficient carrier separation and migration, thereby improving response sensitivity. A PEC aptamer sensor was constructed based on the synthesized heterostructure for ciprofloxacin detection. The detection limit of the CuInS2/RP NS aptamer sensor for ciprofloxacin is 2.03 × 10-15 mg·mL-1, with a linear range from 1.0 × 10-14 to 1.0 × 10-5 mg·mL-1. This work presents a strategy for enhancing the photoelectric response by modulating the interface structure of heterojunctions, thereby opening new prospects for the application of highly sensitive PEC sensors in antibiotic detection.

Association between childhood emotional abuse and non-suicidal self-injury among Guangxi adolescents in China: A moderated mediation model.

BACKGROUND: Childhood Emotional Abuse (CEA) is a known risk factor for Non Suicidal Self-injury (NSSI), which could have devastating repercussions. This study aimed to establish whether Parent-Child Attachment (PCA) and depressive symptoms mediated the CEA-NSSI relationship, as well as whether school connectedness moderated both the direct and indirect relationships between CEA and NSSI. METHODS: Between November and December 2022, 7447 Chinese adolescents in high schools were surveyed through multi-stage cluster random sampling. The participants completed self-reported questionnaires that assessed CEA, PCA, depressive symptoms, school connectedness, and NSSI. Relationships between these variables were examined through moderated mediation analysis using SPSS macro-PROCESS. RESULTS: After controlling for sociodemographic variables, we found that CEA correlated positively with NSSI through two different pathways: the mediating role of depressive symptoms and the chain-mediating role of both PCA and depressive symptoms. Moreover, school connectedness could moderate the direct and indirect relationships between CEA and NSSI. LIMITATIONS: The study's cross-sectional design does not allow for causal inferences. CONCLUSIONS: Overall, PCA, depressive symptoms, and school connectedness could affect the CEA-NSSI relationship.

SLC4A4 as a novel biomarker involved in immune system response and lung adenocarcinoma progression.

BACKGROUND: Altered expression and activity of solute carrier family 4 member 4 (SLC4A4) could affect the growth, survival and metastasis of tumor cells. Currently, the role of SLC4A4 in lung adenocarcinoma (LUAD) immunotherapy and prognosis was not entirely clear. METHODS: We analyzed SLC4A4 expression in LUAD tissues and cell lines using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. The effects of SLC4A4 overexpression on angiogenesis, cell migration, invasion, and epithelial-mesenchymal transition were examined. Public databases helped construct a risk model evaluating SLC4A4's expression on LUAD prognosis and immunotherapy response. Additionally, a xenograft model, flow cytometry, and enzyme-linked immunosorbent assay further explored SLC4A4's role in tumor immune microenvironment infiltration. RESULTS: Upregulation of SLC4A4 promoted apoptosis in the LUAD cell line and significantly inhibited the migration and invasive ability of cancer cells (P<0.01). A total of 10 key genes (including SIGLEC6, RHOV, PIR, MOB3B, MIR3135B, LPAR6, KRT8, ITGA2, CPS1, and C6) were screened according to SLC4A4 expression, immune score and stromal score, and a prognostic model with good outcome was constructed (AUC values of which in the training cohort at 1,3, and 5 years reached 0.73, 0.73, and 0.72, respectively). Importantly, we demonstrated that high expression of SLC4A4 was able to increase the proliferation level and cytokine secretion of CD8+ T cells for the purpose of promoting the immune system response to LUAD. CONCLUSION: Our study revealed that SLC4A4 can serve as a prognostic indicator for LUAD, providing new insights into the treatment and diagnosis of LUAD.

n-Bu4NI/K2S2O8 Mediated Csp2-Csp2 Bond Cleavage - Transformylation from p-Anisaldehyde to Primary Amides.

n-Bu4NI/K2S2O8 mediated transformylation from p-anisaldehyde to primary amides is reported. The mechanistic studies suggest the reaction occurs via a single electron transfer pathway. Based on the DFT electronic structure calculations of various reaction pathways, the most plausible mechanism involves the formation of a phenyl radical cation and an arenium ion as the key intermediates. It represents the first example where p-anisaldehyde is employed as a formyl source via a non-metal mediated Csp2-Csp2 bond cleavage.

New phenols and one aminobenzoic acid derivative isolated from the roots of Rhus chinensis Mill.

Four new phenols and one new aminobenzoic acid derivative, with five known phenols were isolated from the roots of Rhus chinensis Mill. Their structures were elucidated by UV, IR, HRESIMS, 1D and 2D NMR spectra, as well as optical rotations. Compound 4 significantly inhibited mouse ear inflammation (inhibitory rate of 44.03%), and significantly extended the time of pain response (extension rate of 48.55%), showing significant anti-inflammatory and analgesic effects in vivo.

Reduction of precious metal ions in aqueous solutions by contact-electro-catalysis.

Precious metals are core assets for the development of modern technologies in various fields. Their scarcity poses the question of their cost, life cycle and reuse. Recently, an emerging catalysis employing contact-electrification (CE) at water-solid interfaces to drive redox reaction, called contact-electro-catalysis (CEC), has been used to develop metal free mechano-catalytic methods to efficiently degrade refractory organic compounds, produce hydrogen peroxide, or leach metals from spent Li-Ion batteries. Here, we show ultrasonic CEC can successfully drive the reduction of Ag(ac), Rh3+, [PtCl4]2-, Ag+, Hg2+, Pd2+, [AuCl4]-, and Ir3+, in both anaerobic and aerobic conditions. The effect of oxygen on the reaction is studied by electron paramagnetic resonance (EPR) spectroscopy and ab-initio simulation. Combining measurements of charge transfers during water-solid CE, EPR spectroscopy and gold extraction experiments help show the link between CE and CEC. What's more, this method based on water-solid CE is capable of extracting gold from synthetic solutions with concentrations ranging from as low as 0.196 ppm up to 196 ppm, reaching in 3 h extraction capacities ranging from 0.756 to 722.5 mg g-1 in 3 h. Finally, we showed CEC is employed to design a metal-free, selective, and recyclable catalytic gold extraction methods from e-waste aqueous leachates.

The Relationship Between Perceived Stress, Impulsivity, Executive Dysfunction and Non-Suicidal Self-Injury Thoughts Among Chinese College Students: A Gender Difference Study.

Background: The present study aimed to investigate the potential role of perceived stress, impulsivity trait, executive dysfunction in non-suicidal self-injury (NSSI) thoughts among college students, as well as the gender differences. Methods: A sample of 890 university students completed self-report measures of NSSI thoughts in the past month, the level of perceived stress, impulsivity traits, and executive dysfunction. Results: Compared to those with low level of perceived stress, participants with high level of perceived stress reported significant higher levels of impulsivity trait and executive dysfunction, and higher frequency of NSSI thoughts, and there were no gender differences. Male participants with NSSI thoughts, compared to males without NSSI thoughts, reported significant higher levels of perceived stress and executive dysfunction. Female participants with NSSI thoughts, compared to females without NSSI thoughts, reported significant higher levels of perceived stress, impulsivity trait, and executive dysfunction. Hierarchical regression analysis revealed only executive dysfunction was associated with NSSI thoughts in males, while only perceived stress was associated with NSSI thoughts in females. Conclusion: This study revealed different influence factors for NSSI thoughts in male and female college students. NSSI thoughts in males were more likely associated with executive dysfunction while in females were due to recently perceived stress.

Development of an aptamer capable of multidrug resistance reversal for tumor combination chemotherapy.

Multidrug resistance (MDR) is a major factor in the failure of many forms of tumor chemotherapy. Development of a specific ligand for MDR-reversal would enhance the intracellular accumulation of therapeutic agents and effectively improve the tumor treatments. Here, an aptamer was screened against a doxorubicin (DOX)-resistant human hepatocellular carcinoma cell line (HepG2/DOX) via cell-based systematic evolution of ligands by exponential enrichment. A 50 nt truncated sequence termed d3 was obtained with high affinity and specificity for HepG2/DOX cells. Multidrug resistance protein 1 (MDR1) is determined to be a possible recognition target of the selected aptamer. Aptamer d3 binding was revealed to block the MDR of the tumor cells and increase the accumulation of intracellular anticancer drugs, including DOX, vincristine, and paclitaxel, which led to a boost to the cell killing of the anticancer drugs and lowering their survival of the tumor cells. The aptamer d3-mediated MDR-reversal for effective chemotherapy was further verified in an in vivo animal model, and combination of aptamer d3 with DOX significantly improved the suppression of tumor growth by treating a xenograft HepG2/DOX tumor in vivo. This work demonstrates the feasibility of a therapeutic DNA aptamer as a tumor MDR-reversal agent, and combination of the selected aptamer with chemotherapeutic drugs shows great potential for liver cancer treatments.

The dynamics of nocturnal sap flow components of a typical revegetation shrub species on the semiarid Loess Plateau, China.

Introduction: The components of nighttime sap flux (En), which include transpiration (Qn) and stem water recharge (Rn), play important roles in water balance and drought adaptation in plant communities in water-limited regions. However, the quantitative and controlling factors of En components are unclear. Methods: This study used the heat balance method to measure sap flow density in Vitex negundo on the Loess Plateau for a normal precipitation year (2021) and a wetter year (2022). Results: The results showed that the mean values were 1.04 and 2.34 g h-1 cm-2 for Qn, 0.19 and 0.45 g h-1 cm-2 for Rn in 2021 and 2022, respectively, and both variables were greater in the wetter year. The mean contributions of Qn to En were 79.76% and 83.91% in 2021 and 2022, respectively, indicating that the En was mostly used for Qn. Although the vapor pressure deficit (VPD), air temperature (Ta) and soil water content (SWC) were significantly correlated with Qn and Rn on an hourly time scale, they explained a small fraction of the variance in Qn on a daily time scale. The main driving factor was SWC between 40-200 cm on a monthly time scale for the Qn and Rn variations. Rn was little affected by meteorological and SWC factors on a daily scale. During the diurnal course, Qn and Rn initially both declined after sundown because of decreasing VPD and Ta, and Qn was significantly greater than Rn, whereas the two variables increased when VPD was nearly zero and Ta decreased, and Rn was greater than Qn. Discussion: These results provided a new understanding of ecophysiological responses and adaptation of V. negundo plantations to increasing drought severity and duration under climate changes.

Synthetic Cells from Droplet-Based Microfluidics for Biosensing and Biomedical Applications.

Synthetic cells function as biological mimics of natural cells by mimicking salient features of cells such as metabolism, response to stimuli, gene expression, direct metabolism, and high stability. Droplet-based microfluidic technology presents the opportunity for encapsulating biological functional components in uni-lamellar liposome or polymer droplets. Verified by its success in the fabrication of synthetic cells, microfluidic technology is widely replacing conventional labor-intensive, expensive, and sophisticated techniques justified by its ability to miniaturize and perform batch production operations. In this review, an overview of recent research on the preparation of synthetic cells through droplet-based microfluidics is provided. Different synthetic cells including lipid vesicles (liposome), polymer vesicles (polymersome), coacervate microdroplets, and colloidosomes, are systematically discussed. Efforts are then made to discuss the design of a variety of microfluidic chips for synthetic cell preparation since the combination of microfluidics with bottom-up synthetic biology allows for reproductive and tunable construction of batches of synthetic cell models from simple structures to higher hierarchical structures. The recent advances aimed at exploiting them in biosensors and other biomedical applications are then discussed. Finally, some perspectives on the challenges and future developments of synthetic cell research with microfluidics for biomimetic science and biomedical applications are provided.

Difluorocarbene Enables Access to 2,2-Difluorohydrobenzofurans and 2-Fluorobenzofurans from ortho-Vinylphenols.

2-Fluorobenzofurans are the backbone structures of many drug molecules and have many potential therapeutic bioactivities. Despite the potential applications in medicinal chemistry, practical and efficient synthetic methods for the construction of 2-fluorobenzofuran are very limited. Herein, we report an efficient and general method for the construction of 2-fluorobenzofurans. Contrary to the previous functionalizations of the existing backbone of benzofuran, our strategy directly constructs benzofuran scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4 + 1] cyclization from readily accessible ortho-vinylphenols and difluorocarbene. In our strategy, ClCF2H decomposes into difluorocarbene in the presence of base, which is further captured by the oxygen anion from the hydroxy group in ortho-hydroxychalcones; subsequent intramolecular Michael addition to the α, ß-unsaturated system leads to 2,2-difluorohydrobenzofurans, and further fluorine elimination renders 2-fluorobenzofurans by forming one C-O bond and one C-C double bond. Of note, various complex 2,2-difluorohydrobenzofurans and 2-fluorobenzofurans could be readily accessed through our protocol via the late-stage elaborations.

Sulfonium-Stapled Peptides-Based Neoantigen Delivery System for Personalized Tumor Immunotherapy and Prevention.

Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross-presentation, the progress with neoantigen peptide-based vaccines has obviously lagged in clinical trials. Here, a stapling peptide-based nano-vaccine is developed, comprising a self-assembly nanoparticle driven by the nucleic acid adjuvant-antigen conjugate. This nano-vaccine stimulates a strong tumor-specific T cell response by activating antigen presentation and toll-like receptor signaling pathways. By markedly improving the efficiency of antigen/adjuvant co-delivery to the draining lymph nodes, the nano-vaccine leads to 100% tumor prevention for up to 11 months and without tumor recurrence, heralding the generation of long-term anti-tumor memory. Moreover, the injection of nano-vaccine with signal neoantigen eliminates the established MC-38 tumor (a cell line of murine carcinoma of the colon without exogenous OVA protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling peptide-based nano-vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti-tumor immune response for the neoantigen peptide-based personalized tumor immunotherapy.

Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat.

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

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Childhood trauma refers to trauma experiences encountered during childhood and adolescence. Maternal childhood trauma experiences have a lasting impact on the next generation, affecting their physical and mental well-being. The mechanisms involved include the hypothalamic-pituitary-adrenal axis, inflammatory factors, brain structure and function, gene interactions, and parenting styles. This paper systematically reviews the mechanisms of the impact of maternal childhood trauma on intergenerational transmission, providing insights for the prevention of intergenerational transmission of childhood trauma.

Isolation and characterization of dihydrohomoisoflavonoids from Portulaca oleracea L.

Eight pairs of dihydrohomoisoflavonoids (1-8), including four pairs of enantiomeric aglycones [(R,S)-portulacanones B (1) and C (2) and (R,S)-oleracones C (3) and Q (4)] and four pairs of epimeric glycosides [portulacasides A-D and epiportulacasides A-D (5-8)], were obtained from Portulaca oleracea L. Among them, (R,S)-oleracone Q (4) and four pairs of epimeric glycosides (5-8) were reported for the first time. The 50% EtOH fraction from the 70% EtOH extract prevented HepG2 human liver cancer cell damage induced by N-acetyl-p-aminophenol (APAP), and the cell survival rate was 62.3%. Portulacaside B (6a), which was isolated from the 50% EtOH fraction, exhibited hepatoprotective and anti-inflammatory effects. The compound increased the survival rate of APAP-damaged HepG2 human liver cancer cells from 40.0% to 51.2% and reduced nitric oxide production in RAW 264.7 macrophages, resulting in an inhibitory rate of 46.8%.