Reassessing clinical presentations of emamectin benzoate poisoning: A comprehensive study.

BACKGROUND: The mechanism of emamectin benzoate (EMB-a macrocyclic lactone insecticide like abamectin) action involves the disruption of glutamate-gated chloride channels and GABA receptors in insects, leading to paralysis and death. EMB overdose can breach the blood-brain barrier, resulting in severe poisoning and altered consciousness. AIM: Review EMB poisoning presentations in patients and reevaluate clinical manifestations. MATERIALS AND METHODS: This retrospective study reviewed (August 31, 2008-August 31, 2023) medical university hospital records. We analyzed symptoms, patient characteristics, vital signs, Glasgow Coma Scale scores, laboratory findings, and outcomes. RESULTS: Ten patients (males: 6, females: 4, median age = 64.5 years) experienced EMB poisoning. Common symptoms included sore throat, gastrointestinal distress, dyspnea, and altered consciousness; two patients showed laryngeal corrosive injuries. Management involved activated charcoal administration, gastric lavage, and intensive care unit admission. DISCUSSION: Sore throat and corrosive injuries were distinctive presentations of EMB poisoning, warranting vigilance. Potential mechanisms of corrosive injury include skin and eye irritation effects of EMB, the solvents of which might exert corrosive action. CONCLUSION: EMB poisoning manifests as diverse symptoms, including sore throat, gastrointestinal symptoms, central nervous system depression, and potential aspiration pneumonia. Recognizing and promptly managing EMB poisoning are crucial for enhancing patient outcomes and minimizing complications.

Energetically Favored 2D to 3D Transition: Why Silicene Cannot Be Grown on Ag(111).

Silicene, a two-dimensional (2D) Si monolayer with properties similar to those of graphene, has attracted considerable attention because of its compatibility with existing technology. Most growth efforts to date have focused on the Ag(111) substrate, with a 3 × 3 phase widely reported below one monolayer (ML). As the coverage increases, a √3 × âˆš3 pattern frequently emerges, which has been proposed by various experimental investigations as a Si(111)-3×3-Ag reconstructed structure. We report first-principles calculations to understand this series of observations. A major finding from our energetics studies is that Si growth on Ag(111) beyond one ML will switch to the Volmer-Weber mode, forming three-dimensional sp3 films. Combining with the condition that the 3 × 3 monolayer on Ag(111) does not have the correct buckling pattern of freestanding silicene, we conclude that silicene cannot be grown on Ag(111) and that a 2D to 3D transition is energetically favored beyond one ML.

[Brain Fog: A Concept Analysis].

Brain fog is a symptom that has gained increasing attention worldwide since the start of the COVID-19 pandemic, as patients affected by COVID-19 may experience cognitive dysfunction, colloquially known as brain fog, for a period of time after recovery. Brain fog affects activities of daily living and work performance and has the potential to negatively impact society and the economy. However, a clear definition and concept analysis of brain fog is lacking in the literature. In this article, a concept analysis of brain fog is conducted using Walker and Avant's concept analysis steps to verify the source and definition of brain fog, clarify related concepts similar to brain fog, and establish the defining attributes, antecedents, and consequences of this condition. Model, borderline, contrary, and related cases are listed to illustrate and provide related empirical references in the literature. The authors hope this article will provide a clearer understanding of brain fog, which then may be applied in nursing clinical practice and future research to develop strategies and care methods for improving brain fog symptoms.

Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. METHODS: Animal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1ß were detected by western blotting. Serum IL-1ß, IL-6 and S100ß were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1ß were detected by western blotting and the content of IL-1ß in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. RESULTS: Splenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1ß due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. CONCLUSIONS: Our findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

Can We Do Breast-Conserving Surgery Without Intraoperative Frozen Section of Margin?

PURPOSE: This study was a retrospective and nonrandomized study to assess the safety and reliability of identifying the surgical margin in breast cancer breast-conserving surgery (BCS) by using intraoperative ultrasonic location and specimen mammography instead of traditional intraoperative frozen pathological section. METHODS: Among the patients who underwent BCS from May 2019 to October 2021, according to the different methods of evaluating the intraoperative margin, 104 breast cancer patients were included in the frozen edge group, 53 breast cancer patients were included in the freeze-free group, and the surgeon judged whether extended resection was needed based on the results of pathological section or evaluation of intraoperative ultrasound and mammography. The surgical margins of the two groups were judged by postoperative pathological results as the gold standard. RESULTS: The median waiting pathology results time in the frozen edge group was 64 minutes, while the waiting time in the freeze-free group was 30 minutes, and the difference was statistically significant (P < .0001). The postoperative pathological results showed that the positive rate of the surgical margin in the frozen edge group was 0.96%. The coincidence rate of intraoperative frozen and postoperative pathological results was 99.04%. The coincidence rate between intraoperative mammography and postoperative pathological results was 100%. CONCLUSIONS: In BCS, the method of using intraoperative staining markers combined with mammography to evaluate the resection margin is highly accurate, reliable, economical and convenient, and at the same time reduces the waiting time of the operator during the operation. However, this was not a randomized controlled study, and there was patient selection bias, and its safety needs to be confirmed by long-term follow-up. In the future, it is expected to become the mainstream means of evaluating.

Effects of dietary supplementation of fish oil plus vitamin D3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial.

We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.

Surufatinib combined camrelizumab as a valuable third-line rescue therapy for a patient with extensive-stage for small-cell lung cancer: a case report and literature review.

Lung cancer is one of the most common malignant tumors with the highest incidence. Gene mutations are rare in small-cell lung carcinoma (SCLC), resulting in targeted therapy being only a third-line recommendation. Surufatinib (Sulanda) is an oral angio-immune kinase inhibitor used to treat solid tumors. We report a case of SCLC treated with surufatinib combined with camrelizumab, with good therapeutic results in our department. The patient experienced over 18 months of progression-free survival and over 28 months of overall survival. This suggests that surufatinib combined with camrelizumab is an effective third-line treatment for SCLC patients. However, the response rate to surufatinib treatment in all patients with SCLC remains unknown and needs to be determined in a large population.

Association of seafood consumption with cardiovascular disease among adults in Qingdao, China.

BACKGROUND AND AIMS: The relationship between seafood consumption and cardiovascular disease (CVD) is controversial, and studies have not considered competing risk events. Our study examined the association between a full range of seafood consumption and CVD incidence and mortality based on the Qingdao Diabetes Prevention Program. METHODS AND RESULTS: We followed up 5285 participants without CVD at baseline until December 31, 2021. CVD cases and deaths were identified through record linkage with the Qingdao CVD Surveillance System and the Qingdao Death Surveillance System, respectively. Information on seafood consumption was obtained using a food frequency questionnaire. We used the Cox proportional hazard model and the competing risk model to evaluate the association between all types of seafood consumption and CVD incidence and mortality. During a median follow-up of 11.4 years, 122 CVD cases and 75 deaths occurred. After adjustment for potential confounders, compared with nonconsumers, seafood consumption of 300-500 and > 500 g/week was associated with a lower risk of CVD incidence [hazards ratio and 95 % confidence interval (CI): 0.54 (0.29-0.99) and 0.49 (0.26-0.91), respectively]. However, seafood consumption of >500 g/week had a significantly lower risk of CVD mortality [subdistribution hazard ratio and 95 % CI: 0.40 (0.17-0.95)], but it was insignificant in other groups. CONCLUSION: Seafood consumption of 300-500 g/week and >500 g/week was associated with a lower CVD incidence and mortality. Our findings provide evidence of the recommendations of the 2022 Dietary Guidelines for Chinese residents and may guide the promotion of strategies for CVD prevention.

Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer.

Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

The excitatory transmission from basolateral nuclues of amygdala to nucleus accumbens shell regulates propofol self-administration through AMPA receptors.

Propofol addictive properties have been demonstrated in humans and rats. The glutamatergic transmission from basolateral nucleus of amygdala (BLA) to the nucleus accumbens (NAc) modulates reward-seeking behaviour; especially, NAc shell (NAsh) is implicated in reward-seeking response. Previous studies indicated the interactions between AMPA receptors (AMPARs) and dopamine D1 receptor (D1R) in NAc mediated drug addiction, but whether the circuit of BLA-to-NAsh and AMPARs regulate propofol addiction remains unclear. We trained adult male Sprague-Dawley rats for propofol self-administration to examine the changes of action potentials (APs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the NAsh. Thereafter, optogenetic stimulation with adeno-associated viral vectors microinjections in BLA was used to explore the effect of BLA-to-NAsh on propofol self-administration behaviour (1.7 mg/kg/injection). The pretreatment effects with NBQX (0.25-1.0 µg/0.3 µl/site) or vehicle in the NAsh on propofol self-administration behaviour, the expressions of AMPARs subunits and D1R/ERK/CREB signalling pathway in the NAc were detected. The results showed that the number of APs, amplitude and frequency of sEPSCs were enhanced in propofol self-administrated rats. Propofol self-administration was inhibited in the NpHR3.0-EYFP group, but in the ChR2-EYFP group, there was a promoting effect, which could be weakened by NBQX pretreatment. NBQX pretreatment also significantly decreased the expressions of GluA2 subunit and D1R in the NAc but did not change the expressions of GluA1 and ERK/CREB signalling pathway. The evidence supports a vital role of BLA-to-NAsh circuit in regulating propofol self-administration and suggests this central reward processing may function through the interaction between AMPARs and D1R in the NAsh.

Pathologic collision of urinary bladder urothelial carcinoma with small cell carcinoma: a case report.

BACKGROUND: Urothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings. CASE PRESENTATION: Here, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023. DISCUSSION: We hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present. CONCLUSIONS: We recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients.

Effect of Low Protein Diet Supplemented with Ketoanalogs on Endothelial Function and Protein-Bound Uremic Toxins in Patients with Chronic Kidney Disease.

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3-5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b-4 patients on LPD (0.6-0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t-test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD (p < 0.001) and a decrease in FPCS (p = 0.012) and TIS (p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.

The Prospective Associations of Egg Consumption with the Risk of Total Cerebrovascular Disease Morbidity among Chinese Adults.

BACKGROUND: Studies investigating the relationship between egg consumption and the risk of cerebrovascular disease (CED) have yielded inconsistent results. This study evaluated the association between egg consumption and the risk of CED among Chinese adults. METHODS: Data were obtained from China Kadoorie Biobank, Qingdao. A computerised questionnaire was used to collect information regarding egg consumption frequency. CED events were tracked through linkage with the Disease Surveillance Point System and the new national health insurance databases. Cox proportional hazards regression analyses were used to evaluate associations between egg consumption and CED risk controlling for potential confounders. RESULTS: After a median follow-up of 9.2 years, 865 and 1083 CED events among men and women, respectively, were documented. More than 50% of participants consumed eggs daily with an average age of 52.0 (10.4) years at baseline. No association between egg consumption and CED were identified in the whole cohort and women. However, a 28% lower risk of CED was observed in those who consumed eggs at a higher frequency (HR = 0.72, 95% CI: 0.55-0.95) and a significant trend for the association (p for trend = 0.012) in a multivariable model in men. CONCLUSION: Higher frequency of egg consumption was associated with a lower risk of total CED events among men but not women in Chinese adults. The beneficial effect on women warrants further investigations.

Radiation prevents tumor progression by inhibiting the miR­93­5p/EphA4/NF­κB pathway in triple­negative breast cancer.

Breast cancer (BC) is the most common type of cancer in women. Triple­negative BC (TNBC) constitutes 10­15% of all BC cases and is associated with a poor prognosis. It has previously been reported that microRNA (miR)­93­5p is dysregulated in plasma exosomes from patients with BC and that miR­93­5p improves radiosensitivity in BC cells. The present study identified EphA4 as a potential target gene of miR­93­5p and investigated the pathway related to miR­93­5p in TNBC. Cell transfection and nude mouse experiments were performed to verify the role of the miR­93­5p/EphA4/NF­κB pathway. Moreover, miR­93­5p, EphA4 and NF­κB were detected in clinical patients. The results revealed that EphA4 and NF­κB were downregulated in the miR­93­5p overexpression group. By contrast, EphA4 and NF­κB expression levels were not significantly altered in the miR­93­5p overexpression + radiation group compared with those in the radiation group. Furthermore, overexpression of miR­93­5p with concomitant radiation therapy significantly decreased the growth of TNBC tumors in vivo. In conclusion, the present study revealed that miR­93­5p targeted EphA4 in TNBC through the NF­κB pathway. However, radiation therapy prevented tumor progression by inhibiting the miR­93­5p/EphA4/NF­κB pathway. Therefore, it would be interesting to elucidate the role of miR­93­5p in clinical research.

Prediction of Intradialytic Blood Pressure Variation Based on Big Data.

INTRODUCTION: Cardiovascular (CV) events are the major cause of morbidity and mortality associated with blood pressure (BP) in hemodialysis (HD) patients. BP varies significantly during HD treatment, and the dramatic variation in BP is a well-recognized risk factor for increased mortality. The development of an intelligent system capable of predicting BP profiles for real-time monitoring is important. Our aim was to build a web-based system to predict changes in systolic BP (SBP) during HD. METHODS: In this study, dialysis equipment connected to the Vital Info Portal gateway collected HD parameters that were linked to demographic data stored in the hospital information system. There were 3 types of patients: training, test, and new. A multiple linear regression model was built using the training group with SBP change as the dependent variable and dialysis parameters as the independent variables. We tested the model's performance on test and new patient groups using coverage rates with different thresholds. The model's performance was visualized using a web-based interactive system. RESULTS: A total of 542,424 BP records were used for model building. The accuracy was greater than 80% in the prediction error range of 15%, and 20 mm Hg of true SBP in the test and new patient groups for the model of SBP changes suggested the good performance of our prediction model. In the analysis of absolute SBP values (5, 10, 15, 20, and 25 mm Hg), the accuracy of the SBP prediction increased as the threshold value increased. DISCUSSION: This databae supported our prediction model in reducing the frequency of intradialytic SBP variability, which may help in clinical decision-making when a new patient receives HD treatment. Further investigations are needed to determine whether the introduction of the intelligent SBP prediction system decreases the incidence of CV events in HD patients.

Creating a Nanoscale Lateral Junction in a Semiconductor Monolayer with a Large Built-in Potential.

The ability to engineer atomically thin nanoscale lateral junctions is critical to lay the foundation for future two-dimensional (2D) device technology. However, the traditional approach to creating a heterojunction by direct growth of a heterostructure of two different materials constrains the available band offsets, and it is still unclear if large built-in potentials are attainable for 2D materials. The electronic properties of atomically thin semiconducting transition metal dichalcogenides (TMDs) are not static, and their exciton binding energy and quasiparticle band gap depend strongly on the proximal environment. Recent studies have shown that this effect can be harnessed to engineer the lateral band profile of a monolayer TMD to create a lateral electronic junction. Here we demonstrate the synthesis of a nanoscale lateral junction in monolayer MoSe2 by intercalating Se at the interface of an hBN/Ru(0001) substrate. The Se intercalation creates a spatially abrupt modulation of the local hBN/Ru work function, which is imprinted directly onto an overlying MoSe2 monolayer to create a lateral junction with a large built-in potential of 0.83 ± 0.06 eV. We spatially resolve the MoSe2 band profile and work function using scanning tunneling spectroscopy to map out the nanoscale depletion region. The Se intercalation also modifies the dielectric environment, influencing the local band gap renormalization and increasing the MoSe2 band gap by ∼0.26 ± 0.1 eV. This work illustrates that environmental proximity engineering provides a robust method to indirectly manipulate the band profile of 2D materials outside the limits of their intrinsic properties.

Mutant NPM1 maintains RASGRP3 protein stability via interaction with MID1 to promote acute myeloid leukemia cell proliferation and autophagy.

Acute myeloid leukemia is a heterogeneous hematologic malignancy with high mortality in the world. NPM1 gene mutations are a frequent occurrence in acute myeloid leukemia, leading to abnormal autophagy, while the mechanism of NPM1 mutation-driven acute myeloid leukemia pathogenesis remains to be fully elucidated. GEO microarrays were used to screen for dysregulated autophagy-related genes in NPM1-mutant acute myeloid leukemia and analysis of RASGRP3 expression and prognosis. Next, we explored the potential molecular mechanisms relationship between RASGRP3 and NPM1 through utilizing immunoprecipitation, Western blot, and cycloheximide assay. Further, CCK8, EdU staining, immunofluorescence, and Western blot were performed to explore the effect of RASGRP3 on cell proliferation and apoptosis in NPM1-mutated acute myeloid leukemia. Finally, Western blot was used to study the mechanism of action of RASGRP3. RASGRP3 expression was upregulated in NPM1-mutated acute myeloid leukemia. Mislocalized NPM1-mA in the cytoplasm could bind to E3 ubiquitin-protein ligase MID1 to block degradation of the RASGRP3 protein. RASGRP3 could also activate the EGFR-STAT3 axis to promote proliferation and autophagy in acute myeloid leukemia. In conclusion, our results identified RASGRP3 as a proto-oncogene in NPM1-mutated acute myeloid leukemia. The RASGRP3-EGFR/STAT3 axis may be a promising therapeutic target for this unique leukemic subtype.

Development and systematic characterization of GelMA/alginate/PEGDMA/xanthan gum hydrogel bioink system for extrusion bioprinting.

Gelatin methacryloyl (GelMA)/alginate-based hydrogels have shown great promise in bioprinting, but their printability is limited at room temperature. In this paper, we present our development of a room temperature printable hydrogel bioink by introducing polyethylene glycol dimethacrylate (PEGDMA) and xanthan gum into the GelMA/alginate system. The inclusion of PEGDMA facilitates tuning of the hydrogel's mechanical property, while xanthan gum improves the viscosity of the hydrogel system and allows easy extrusion at room temperature. To fine-tune the mechanical and degradation properties, methacrylated xanthan gum was synthesized and chemically crosslinked to the system. We systematically characterized this hydrogel with attention to printability, strut size, mechanical property, degradation and cytocompatibility, and achieved a broad range of compression modulus (∼10-100 kPa) and degradation profile (100% degradation by 24 h-40% by 2 weeks). Moreover, xanthan gum demonstrated solubility in ionic solutions such as cell culture medium, which is essential for biocompatibility. Live/dead staining showed that cell viability in the printed hydrogels was over 90% for 7 days. Metabolic activity analysis demonstrated excellent cell proliferation and survival within 4 weeks of incubation. In summary, the newly developed hydrogel system has demonstrated distinct features including extrusion printability, widely tunable mechanical property and degradation, ionic solubility, and cytocompatibility. It offers great flexibility in bioprinting and tissue engineering.

Long Non-coding RNA LINC01224 Promotes the Malignant Behaviors of Triple Negative Breast Cancer Cells via Regulating the miR-193a-5p/NUP210 Axis.

Triple negative breast cancer (TNBC) is a prevalent malignant tumor in women and is characterized by high incidence and mortality. Current evidence has suggested that multiple long noncoding RNAs (lncRNAs) play regulatory roles in TNBC, while the specific mechanism of LINC01224 in TNBC remains unclear. In this study, LINC01224 was highly expressed in TNBC cells. Moreover, LINC01224 downregulation inhibited TNBC cell proliferation, migration, and invasion, and promoted cell apoptosis. Additionally, LINC01224 stabilized NUP210 mRNA through interaction with miR-193a-5p, thereby aggravating the malignant phenotypes of TNBC. Overall, LINC01224 functions as a tumor promoter for TNBC.