Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides.

A three-component strategy was developed to enable hydrodefluoroamination of ß-trifluoromethyl enones by selectively activating two C(sp3)-F bonds in the trifluoromethyl group. The method involved a sequence of carbonyl reduction, hydrodefluorination, and defluoroamination under transition-metal-free conditions. Synthetically useful (E)-stereospecific α-fluoroenamides were obtained in good yields with diverse functional group tolerance, which could be easily transformed into valuable organofluorides and heterocycles. The carbonyl auxiliary exerts both electronic and steric impacts on the CF3-alkenes, allowing for controllable and selective defluorination.

Tailoring the spectro-temporal mode of photon pairs generated from interspatial-mode four-wave mixing.

We investigate the spectro-temporal mode property of the photon pairs generated via interspatial-mode spontaneous four-wave mixing (FWM) in a few-mode fiber (FMF) that supports two linearly polarized spatial modes in the 1550 nm telecom band. The two pulsed pumps for the process are in distinct spatial modes, while the created signal and idler photon pairs are also occupying different spatial modes. By exploiting the unique inter-mode phase matching condition in the FMF, we can tailor the spectro-temporal mode structure of the photon pairs by changing the pulse duration (spectral bandwidth) of the two pumps. Especially, photon pairs with a nearly round-shaped factorable joint spectrum are experimentally realized. The techniques are valuable for generating and manipulating quantum states in multi-mode waveguides and exploiting the spatial degree of freedom in quantum information processing.

Panoramic tumor microenvironment in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance to various treatment modalities. The genetic heterogeneity of PDAC, coupled with the presence of a desmoplastic stroma within the tumor microenvironment (TME), contributes to an unfavorable prognosis. The mechanisms and consequences of interactions among different cell types, along with spatial variations influencing cellular function, potentially play a role in the pathogenesis of PDAC. Understanding the diverse compositions of the TME and elucidating the functions of microscopic neighborhoods may contribute to understanding the immune microenvironment status in pancreatic cancer. As we delve into the spatial biology of the microscopic neighborhoods within the TME, aiding in deciphering the factors that orchestrate this intricate ecosystem. This overview delineates the fundamental constituents and the structural arrangement of the PDAC microenvironment, highlighting their impact on cancer cell biology.

Growth of Carbon Nanofibers and Carbon Nanotubes by Chemical Vapour Deposition on Half-Heusler Alloys: A Computationally Driven Experimental Investigation.

The possibility of directly growing carbon nanofibers (CNFs) and carbon nanotubes (CNTs) on half-Heusler alloys by Chemical Vapour Deposition (CVD) is investigated for the first time, without using additional catalysts, since the half-Heusler alloys per se may function as catalytic substrates, according to the findings of the current study. As a carbon source, acetylene is used in the temperature range of 700-750 °C. The n-type half-Heusler compound Zr0.4Ti0.60.33Ni0.33Sn0.98Sb0.020.33 is utilized as the catalytic substrate. At first, a computational model is developed for the CVD reactor, aiming to optimize the experimental process design and setup. The experimental process conditions are simulated to investigate the reactive species concentrations within the reactor chamber and the activation of certain reactions. SEM analysis confirms the growth of CNFs with diameters ranging from 450 nm to 1 µm. Raman spectroscopy implies that the formed carbon structures resemble CNFs rather than CNTs, and that amorphous carbon also co-exists in the deposited samples. From the characterization results, it may be concluded that a short reaction time and a low acetylene flow rate lead to the formation of a uniform CNF coating on the surface of half-Heusler alloys. The purpose of depositing carbon nanostructures onto half-Heusler alloys is to improve the current transfer, generated from these thermoelectric compounds, by forming a conductive coating on their surface.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Mn(II)-Aloe-Emodin Nanoscale Coordination Polymer Enhances Ferroptosis by Synergistically Enhancing Reactive Oxygen Species Generation via the Nrf2-GPX4 Axis.

Ferroptosis induction is particularly promising for cancer therapy when the apoptosis pathway is compromised. Current strategies in nanomedicine for inducing ferroptosis primarily focus on promoting the accumulation of reactive oxygen species (ROS). However, the presence of intracellular antioxidants, such as nuclear factor erythroid 2-related factor 2 (Nrf2), can limit the effectiveness of such therapy by activating detoxification systems and eliminating ROS. To overcome this challenge, we developed a synergistic ferroptosis-inducing agent by modifying manganese (Mn2+)-1,8-dihydroxy-3-hydroxymethyl-anthraquinone (aloe-emodin, AE) with polyvinyl pyrrolidone (PVP) to create nanoparticles (MAP NPs). In the tumor microenvironment, these NPs degraded and released AE and Mn(II), facilitating the generation of ROS and Mn(IV) through a Fenton-like reaction between hydrogen peroxide (H2O2) and Mn(II). Mn(IV) subsequently interacts with glutathione (GSH) to induce a cyclic catalytic effect, and the depletion of GSH diminished the activation of glutathione-dependent peroxidase 4 (GPX4). Furthermore, AE inhibits the activity of Nrf2 and depleted GSH, thereby synergistically enhancing antitumor efficacy. Here it is demonstrated that MAP NPs effectively generate a robust ROS storm within tumor cells, suggesting that high-performance ferroptosis therapy is effective. Additionally, the inclusion of Mn(II) in the MAP NPs enables real-time monitoring of therapeutic efficacy via magnetic resonance T1-weighted contrast imaging.

Genotypic and phenotypic characteristics of sodium channel-associated epilepsy in Chinese population.

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

Seed physiological traits and environmental factors influence seedling establishment of vegetable soybean (Glycine max L.).

Edamame (Glycine max (L.) Merr.), a specialty soybean prized for its nutritional value and taste, has witnessed a surge in demand within the U.S. However, subpar seedling stands have hindered its production potential, necessitating increased inputs for farmers. This study aims to uncover potential physiological factors contributing to low seedling emergence in edamame. We conducted comprehensive assessments on thirteen prominent edamame genotypes alongside two food-grade and two grain-type soybean genotypes, focusing on germination and emergence speed in both laboratory and field settings. Additionally, we employed single electrical conductivity tests and identified and quantified seed leachate components to distinguish among soybean types. Furthermore, using a LabField™ simulation table, we examined seed emergence across a wide soil temperature range (5°C to 45°C) for edamame and other soybean types. All seeds were produced under the same environmental conditions, harvested in Fall 2020, and stored under uniform conditions to minimize quality variations. Our findings revealed minimal divergence in emergence percentages among the seventeen genotypes, with over 95% germination and emergence in laboratory conditions and over 70% emergence in the field. Nonetheless, edamame genotypes typically exhibited slower germination speeds and higher leachate exudates containing higher soluble sugars and amino acids. Seed size did not significantly impact total emergence but was negatively correlated with germination and emergence speed, although this effect could be mitigated under complex field conditions. Furthermore, this study proposed differences that distinguish edamame from other soybean types regarding ideal and base temperatures, as well as thermal time. The finds offer valuable insights into edamame establishment, potentially paving the way for supporting local edamame production in the U.S.

Tailoring Stress-Relieved Structure for SnSe Toward High Performance Potassium Ion Batteries.

Metal chalcogenides as an ideal family of anode materials demonstrate a high theoretical specific capacity for potassium ion batteries (PIBs), but the huge volume variance and poor cyclic stability hinder their practical applications. In this study, a design of a stress self-adaptive structure with ultrafine SnSe nanoparticles embedded in carbon nanofiber (SnSe@CNF) via the electrospinning technology is presented. Such an architecture delivers a record high specific capacity (272 mAh g-1 at 50 mA g-1) and high-rate performance (125 mAh g-1 at 1 A g-1) as a PIB anode. It is decoded that the fundamental understanding for this great performance is that the ultrafine SnSe particles enhance the full utilization of the active material and achieve stress relief as the stored strain energy from cycling is insufficient to drive crack propagation and thus alleviates the intrinsic chemo-mechanical degradation of metal chalcogenides.

miR-181d targets BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to Cryptosporidium parvum infection via the intrinsic apoptosis pathway.

Cryptosporidium parvum is an important zoonotic pathogen that is studied worldwide. MicroRNAs (miRNAs) act as post-transcriptional regulators and may play a key role in modulating host epithelial responses following Cryptosporidium infection. Our previous study has shown that C. parvum downregulates the expression of miR-181d through the p50-dependent TLRs/NF-κB pathway. However, the mechanism by which miR-181d regulates host cells in response to C. parvum infection remains unclear. The present study found that miR-181d downregulation inhibited cell apoptosis and increased parasite burden in HCT-8 cells after C. parvum infection. Bioinformatics analysis and luciferase reporter assays have shown that BCL2 was a target gene for miR-181d. Moreover, BCL2 overexpression and miR-181d downregulation had similar results. To further investigate the mechanism by which miR-181d regulated HCT-8 cell apoptosis during C. parvum infection, the expression of molecules involved in the intrinsic apoptosis pathway was detected. Bax, caspase-9, and caspase-3 expression was decreased at 4, 8, 12, and 24 hpi and upregulated at 36 and 48 hpi. Interfering with the expression of miR-181d or BCL2 significantly affected the expression of molecules in the intrinsic apoptosis pathway. These data indicated that miR-181d targeted BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to C. parvum infection via the intrinsic apoptosis pathway. These results allowed us to further understand the regulatory mechanisms of host miRNAs during Cryptosporidium infection, and provided a theoretical foundation for the design and development of anti-cryptosporidiosis drugs.

Correction: A Multilabel Text Classifier of Cancer Literature at the Publication Level: Methods Study of Medical Text Classification.

[This corrects the article DOI: 10.2196/44892.].

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Dietary intervention rescues a bone porosity phenotype in a murine model of Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a complex genetic disorder that affects a range of tissues including muscle and bone. Recent preclinical and clinical studies have shown that Nf1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. These can be subsequently rescued by dietary interventions aimed at modulating lipid availability and metabolism. It was speculated that the modified diet may rescue defects in cortical bone as NF1 deficiency has been reported to affect genes involved with lipid metabolism. Bone specimens were analyzed from wild type control mice as well as Nf1Prx1-/- (limb-targeted Nf1 knockout mice) fed standard chow versus a range of modified chows hypothesized to influence lipid metabolism. Mice were fed from 4 weeks to 12 weeks of age. MicroCT analysis was performed on the cortical bone to examine standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae, and larger open pores). Nf1Prx1-/- bones were found to have inferior bone properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. These measures were rescued by dietary interventions including a L-carnitine + medium-chain fatty acid supplemented chow previously shown to improve muscle histology function. Histological staining visualized these changes in bone porosity. These data support the concept that lipid metabolism may have a mechanistic impact on bone porosity and quality in NF1.

The Development of Novel Cu/GO Nano-Composite Coatings by Brush Plating with High Wear Resistance for Potential Brass Sliding Bearing Application.

Low friction and high wear resistance are critical properties for sliding bearings. In this research, advanced Cu/GO nanocomposite coatings have been developed by a brush plating method to improve the tribological performance of brass-based sliding bearings. A series of brush plating studies under voltages from 2 to 6 V with different GO concentrations (0.2-0.8 g/L) was conducted, and the coating microstructures were characterised by SEM, EDX, GDOES and XRD and the tribological behaviour of the Cu/GO composite coatings were evaluated using dry ball-on-plane tribological tests The experimental results have demonstrated that GO can be successfully introduced into the whole composite coating layer; the Cu/GO composite coatings can reduce the friction of brass and increase its wear resistance by two orders of magnitude, mainly due to the self-lubricating GO added into the coatings.

Silver-promoted ceramic conversion treatment of Ti6Al4V alloy and its mechanical performance.

In this paper, the Ti6Al4V alloy surface was modified via ceramic conversion treatment (CCT) with or without a pre-deposited silver layer. After characterizing the surface morphologies, microstructure and phase constituents of the ceramic oxide layer formed at 620 °C, we investigated the surface hardness and the cross-sectional nano-hardness profile under the oxide layer. The static load-bearing capacity of the oxide layers was examined by applying discrete loads via a Vickers indenter and observing the indentations. A scratch test was used to evaluate the load-bearing capacity and the adhesion/cohesion of the oxide layers. The wettability of the surface changed due to the incorporation of silver and the change of surface morphology. Reciprocating friction and wear test was used to assess the tribological properties. Small and dispersed silver nanoparticles and clusters were found in the oxide layer of the Ag pre-deposited Ti6Al4V samples, and they had much better tribological properties in terms of reduced coefficient of friction and wear volume. With the assistance of silver, the efficiency of the CCT was significantly improved.

Prediction and analysis of risk factors for diabetic retinopathy based on machine learning and interpretable models.

Objective: Diabetic retinopathy is one of the major complications of diabetes. In this study, a diabetic retinopathy risk prediction model integrating machine learning models and SHAP was established to increase the accuracy of risk prediction for diabetic retinopathy, explain the rationality of the findings from model prediction and improve the reliability of prediction results. Methods: Data were preprocessed for missing values and outliers, features selected through information gain, a diabetic retinopathy risk prediction model established using the CatBoost and the outputs of the mode interpreted using the SHAP model. Results: One thousand early warning data of diabetes complications derived from diabetes complication early warning dataset from the National Clinical Medical Sciences Data Center were used in this study. The CatBoost-based model for diabetic retinopathy prediction performed the best in the comparative model test. ALB_CR, HbA1c, UPR_24, NEPHROPATHY and SCR were positively correlated with diabetic retinopathy, while CP, HB, ALB, DBILI and CRP were negatively correlated with diabetic retinopathy. The relationships between HEIGHT, WEIGHT and ESR characteristics and diabetic retinopathy were not significant. Conclusion: The risk factors for diabetic retinopathy include poor renal function, elevated blood glucose level, liver disease, hematonosis and dysarteriotony, among others. Diabetic retinopathy can be prevented by monitoring and effectively controlling relevant indices. In this study, the influence relationships between the features were also analyzed to further explore the potential factors of diabetic retinopathy, which can provide new methods and new ideas for the early prevention and clinical diagnosis of subsequent diabetic retinopathy.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study.

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination.

Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.

Xanthohumol Promotes Skp2 Ubiquitination Leading to the Inhibition of Glycolysis and Tumorigenesis in Ovarian Cancer.

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.