Entropy-Driven Strongly Confined Low-Toxicity Pure-Red Perovskite Quantum Dots for Spectrally Stable Light-Emitting Diodes.

Spectrally stable pure-red perovskite quantum dots (QDs) with low lead content are essential for high-definition displays but are difficult to synthesize due to QD self-purification. Here, we make use of entropy-driven quantum-confined pure-red perovskite QDs to fabricate light-emitting diodes (LEDs) that have low toxicity and are efficient and spectrum-stable. Based on experimental data and first-principles calculations, multiple element alloying results in a 60% reduction in lead content while improving QD entropy to promote crystal stability. Entropy-driven QDs exhibit photoluminescence with 100% quantum yields and single-exponential decay lifetimes without alteration of their morphology or crystal structure. The pure-red LEDs utilizing entropy-driven QDs have spectrally stable electroluminescence, achieving a brightness of 4932 cd/m2, a maximum external quantum efficiency of over 20%, and a 15-fold longer operational lifetime than the CsPbI3 QD-based LEDs. These achievements demonstrate that entropy-driven QDs can mitigate local compositional heterogeneity and ion migration.

Centrifugo-Pneumatic Reciprocating Flowing Coupled with a Spatial Confinement Strategy for an Ultrafast Multiplexed Immunoassay.

Immunoassays serve as powerful diagnostic tools for early disease screening, process monitoring, and precision treatment. However, the current methods are limited by high costs, prolonged processing times (>2 h), and operational complexities that hinder their widespread application in point-of-care testing. Here, we propose a novel centrifugo-pneumatic reciprocating flowing coupled with spatial confinement strategy, termed PRCM, for ultrafast multiplexed immunoassay of pathogens on a centrifugal microfluidic platform. Each chip consists of four replicated units; each unit allows simultaneous detection of three targets, thereby facilitating high-throughput parallel analysis of multiple targets. The PRCM platform enables sequential execution of critical steps such as solution mixing, reaction, and drainage by coordinating inherent parameters, including motor rotation speed, rotation direction, and acceleration/deceleration. By integrating centrifugal-mediated pneumatic reciprocating flow with spatial confinement strategies, we significantly reduce the duration of immune binding from 30 to 5 min, enabling completion of the entire testing process within 20 min. As proof of concept, we conducted a simultaneous comparative test on- and off-the-microfluidics using 12 negative and positive clinical samples. The outcomes yielded 100% accuracy in detecting the presence or absence of the SARS-CoV-2 virus, thus highlighting the potential of our PRCM system for multiplexed point-of-care immunoassays.

Drip-Dry Strategy Assisted Blu-Ray Disc Biosensor for Fast Point of Care Testing.

Discs and numerous other consumer products have been developed for point of care testing (POCT) to replace traditional large and expensive biochemical devices in certain scenarios. Herein, we propose a drip-dry strategy (2D strategy) assisted Blu-ray disc (BD) biosensor, termed BDB, for rapid and portable POCT within 30 min with the cost of a single test < $1. The platform utilizes the covered area formed by the deposition of the substance to be measured on the activated BD surface after the evaporation of water and realizes the quantitative detection of the target through the error readout of free disc quality diagnosis software. As a proof of concept, we first demonstrated the feasibility of direct quantitative detection of substances in solution in a single system through the detection of pure proteins avoiding colorimetric reagent used in traditional optical detection. For the complex mixed systems, we then innovatively utilize the principle that soluble targets promote/inhibit the dissolution of insoluble precipitates to achieve specific detection of targets and successfully apply BDB to the indirect quantitative detection of glutathione (GSH) with LOD of 0.447 mM in the range of 2-16 mM and organophosphorus pesticides (OPs) with LOD of 2.122 × 10-7 M in the range of 1.289 × 10-7-1.289 × 10-4 M. The BDB is widely applicable, easy to operate, and less time-consuming, which is anticipated to provide an alternative method for early, on-site detection or screening.

A positive feedback loop between miR-574-3p and HIF-1α in promoting angiogenesis under hypoxia.

In our previous report, we presented evidence supporting the role of miR-574-3p in downregulating the expression of cullin 2 (CUL2) in gastric cancer (GC) cells. Expanding on those findings, the present study aims to confirm the direct interaction between miR-574-3p and the 3' untranslated region (3'UTR) of CUL2, which leads to the suppression of CUL2 expression and destabilization of the VCBCR complex. Based on these discoveries, we propose a novel pathway involving miR-574-3p, HIF-1α, and VEGF that contributes to angiogenesis. Through a series of meticulous experiments, we successfully validate this hypothesis. Specifically, our observations indicate that overexpression of miR-574-3p in GC cells induces an upregulation of HIF-1α and VEGF, resulting in enhanced proliferation, migration, invasion, and tube formation of HUVEC cells. Furthermore, employing a mouse model, we demonstrate that miR-574-3p facilitates the recruitment of endothelial cells towards matrigel xenografts. Additionally, we note a parallel increase in miR-574-3p and HIF-1α levels across multiple cell lines (including AGS, SGC-7901, Hela, and 293T cells) subjected to hypoxic conditions (2 % O2 or CoCl2 treatment), as well as in the myocardial muscles of sodium nitrite-induced hypoxic mice. Further investigations reveal that HIF-1α upregulates miR-574-3p expression by directly binding to the miR-574 promoter. Collectively, these findings strongly support the existence of a positive feedback loop between miR-574-3p and HIF-1α, which facilitates angiogenesis under hypoxic conditions.

c-Myc protects hepatocellular carcinoma cell from ferroptosis induced by glutamine deprivation via upregulating GOT1 and Nrf2.

BACKGROUND: Glutamine metabolism is critical for development of hepatocellular carcinoma (HCC), which makes it a novel promising treatment target. However, clinical evidence suggested glutamine withdrawal therapy does not achieved the desired tumor suppression. Therefore, it is valuable to investigate the survival mechanisms of tumors with glutamine deprivation. METHODS: The HCC cells were cultured in glutamine-free medium or supplemented with glutamine metabolites or ferroptosis inhibitors. The parameters related to ferroptosis and the activity of GSH synthesis-related enzymes of the HCC cells were detected by corresponding kits. The expressions of glutamate oxaloacetate transaminase 1 (GOT1), c-Myc and Nrf2 were detected by western blot and qRT-PCR. The chromatin immunoprecipitation and luciferase reporter assays were performed to investigate the correlation between c-Myc and GOT1. The siRNAs of c-Myc and GOT1 were used to explore their roles in GSH (GSH) synthesis and ferroptosis in vitro and in vivo. RESULTS: Glutamine deprivation-induced ferroptosis did not completely inhibit HCC cells proliferation. Glutamine deprivation activated the expression of c-Myc, which promoted the transcription of GOT1 and Nrf2, consequently maintaining the GSH synthesis and inhibiting ferroptosis. In addition, combined inhibition of GOT1 with glutamine deprivation could result in better inhibition of HCC in vitro and in vivo. CONCLUSIONS: In our work, the results indicate that GOT1 induced by c-Myc may play an important role in combating ferroptosis due to glutamine deprivation, making it a significant target in glutamine withdrawal therapy. This study provides a theoretical foundation for the clinical targeted therapy for HCC.

Raddeanin A (RA) reduced acute inflammatory injury in mouse experimental cerebral hemorrhage by suppression of TLR4.

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.

AGC1-mediated Metabolic Reprogramming and Autophagy Sustain Survival of Hepatocellular Carcinoma Cells under Glutamine Deprivation.

The dependence of hepatocellular carcinoma (HCC) cells on glutamine suggests the feasibility of targeting glutamine metabolism for therapy. However, drugs inhibiting glutamine uptake and breakdown have not shown promising outcomes. Therefore, investigating the mechanism of glutamine metabolism reprogramming in HCC cells is crucial. We used bioinformatics approaches to investigate the metabolic flux of glutamine in HCC cells and validated it using qRT-PCR and western blotting. HCC cells were cultured in glutamine-deprived medium, and changes in glutamate and ATP levels were monitored. Western blotting was employed to assess the expression of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and autophagy-related proteins. The impact of Solute carrier family 25 member 12 (AGC1) on HCC cell proliferation was studied using CCK-8 and colony formation assays. Furthermore, the effects of AGC1 knockdown via siRNA on metabolic reprogramming and energy supply during glutamine deprivation in HCC were explored. During glutamine deprivation, HCC cells sustain cytosolic asparagine synthesis and ATP production through AGC1. Low ATP levels activate AMPK and inhibit mTOR activation, inducing autophagy to rescue HCC cell survival. Knockdown of AGC1 inhibits mitochondrial aspartate output and continuously activates autophagy, rendering HCC cells more sensitive to glutamine deprivation. AGC1 serves as a critical node in the reprogramming of glutamine metabolism and energy supply in HCC cells. This study provides theoretical support for overcoming resistance to drugs targeting glutamine metabolism.

A novel signature constructed by cuproptosis-related RNA methylation regulators suggesting downregulation of YTHDC2 may induce cuproptosis resistance in colorectal cancer.

BACKGROUND: A newly identified type of cell death due to intracellular copper accumulation is known as cuproptosis and RNA methylation is a post-transcriptional modification mechanism, both of which perform vital roles in the immune microenvironment of colorectal cancer (CRC), but the link between the two needs more research. METHODS: TCGA database provided RNA-seq data and details clinically of CRC samples. Cuproptosis-related RNA methylation regulators (CRRMRs) were identified by correlation analysis. We screened 6 CRRMRs for prognostic model construction by employing LASSO-Cox regression analysis and calculated risk scores by CRRMRs (CuMS). GSE39582 and GSE38832 cohort were used as external validation sets. This research concentrated on the connection between the prognostic model and somatic mutation, anti-cancer drug sensitivity, immune infiltration, immune checkpoint expression. In addition, we investigated the differential expression of YTHDC2 in epithelial cell subpopulations by single-cell analysis with GSE166555, calculated cuproptosis scores and performed pathway enrichment. In vitro experiments were performed to explore the consequences of knockdown of YTHDC2 on CRC cell proliferation and migration, as well as changes in CRC cell viability in response to elesclomol after knockdown of YTHDC2. In vivo experiments, we constructed the cell line-derived xenograft model to further validate the results of the in vitro experiments. RESULTS: The prognosis of CRC can be predicted by CuMS, which GSE39582 and GSE38832 confirmed. Two CuMS groups showed different tumor mutation burden (TMB) and immune infiltration. CuMS was connected to emerging immune checkpoints CD47 and PVR, therefore, it can be clinically complementary to TMB and microsatellite instability (MSI) status. In single-cell analysis, a subpopulation of epithelial cells with high YTHDC2 expression had a high cuproptosis score. In vitro experiments, knocking down YTHDC2 promoted cell proliferation and migration in CRC, and weaken the inhibitory effect of elesclomol and elesclomol-Cu on cell viability, which in vivo experiments validated. CONCLUSION: We developed a prognostic model constructed by 6 CRRMRs to assess overall survival and immune microenvironment of CRC patients. YTHDC2 might regulate cuproptosis in multiple ways.

Predictive factors for herpes simplex virus reactivation in patients with trigeminal neuralgia after surgery.

OBJECTIVE: This study aimed to investigate the predictive factors associated with the reactivation of herpes simplex virus (HSV) in patients with trigeminal neuralgia (TN) after surgery, and to determine whether there is a correlation between reactivation and surgical efficacy. METHODS: This study included 190 patients who underwent surgery between January 2020 and December 2021. Postoperative HSV reactivation was defined as the presence of perioral or gingival herpes and herpes labialis within 1 week postoperatively. Logistic regression analysis was used to evaluate clinical characteristics as potential predictors of HSV reactivation. Additionally, Spearman's rank correlation coefficient was used to determine any correlation between the postoperative barrow neurological institute (BNI) pain intensity score and HSV reactivation. RESULTS: Of the 190 patients, 56 (29.5%) experienced postoperative HSV reactivation. Both univariate and multivariate analyses identified several significant predictors of HSV reactivation, such as a history of HSV infection, previous trigeminal nerve-damaging surgery, the use of internal neurolysis (IN) as a surgical technique, and an operation time of ≥25 min. No significant correlation was found between HSV reactivation and pain relief, as measured by BNI scores. CONCLUSIONS: HSV reactivation was observed in a considerable proportion of patients with TN. Long operative times (≥25 min), the use of IN as a surgical technique, a history of HSV infection, and previous trigeminal nerve-damaging surgery were identified as risk factors. Further research is needed to optimize surgical procedures and develop targeted management protocols to reduce the risk of HSV reactivation.

Atmospheric Pressure Enhanced Self-Sealing Rotation-SlipChip with Programmable Concentration Gradient Generation for Microbiological Applications.

In microbiological research, traditional methods for bacterial screening and antibiotic susceptibility testing are resource-intensive. Microfluidics offers an efficient alternative with rapid results and minimal sample consumption, but the demand for cost-effective, user-friendly platforms persists in communities and hospitals. Inspired by the Magdeburg hemispheres, the strategy adapts to local conditions, leveraging omnipresent atmospheric pressure for self-sealing of Rotation-SlipChip (RSC) equipped with a 3D circular Christmas tree-like microfluidic concentration gradient generator. This innovative approach provides an accessible and adaptable platform for microbiological research and testing in diverse settings. The RSC can avoid leakage concerns during multiple concentration gradient generation, chip-rotating, and final long-term incubation reaction (≥24 h). Furtherly, RSC subtypes adapted to different reactions can be fabricated in less than 15 min with cost less than $1, the result can be read through designated observational windows by naked-eye. Moreover, the RSC demonstrates its capability for evaluating bacterial biomarker activity, enabling the rapid assessment of ß-galactosidase concentration and enzyme activity within 30 min, and the limit of detection can be reduced by 10-fold. It also rapidly determines the minimum antibiotic inhibitory concentration and antibiotic combined medications results within 4 h. Overall, these low-cost and user-friendly RSC make them invaluable tools in determinations at previously impractical environment.

Effect and mechanism of eugenol on storage quality of fresh-peeled Chinese water chestnuts.

The study aimed to investigate the effect and mechanism of eugenol treatment on fresh-peeled Chinese water chestnuts (CWCs). The results found that eugenol treatment maintained the appearance of fresh-peeled CWCs, accompanied by higher L* value, total solids and O2 contents, as well as lower browning degree, weight loss rate, CO2 content, a* and b* values. In addition, eugenol treatment significantly reduced the activities of peroxidase, phenylalanine ammonia-lyase, and polyphenol oxidase, as well as the total content of soluble quinone in fresh-peeled CWCs. Meanwhile, fresh-peeled CWCs treated with eugenol showed markedly lower content of total flavonoids, which may be related to yellowing. Furthermore, eugenol treatment suppressed the rates of O2·- and OH·- production as well as the contents of H2O2 and malondialdehyde in fresh-peeled CWCs. During the storage, eugenol treatment not only increased the activities of catalase, superoxide dismutase, ascorbate peroxidase and glutathione reductase as well as the DPPH free radical scavenging rate, but also increased the total phenolics, ascorbic acid and glutathione contents. In summary, eugenol treatment delayed the surface discoloration of fresh-peeled CWCs by improving the antioxidant capacity, inhibiting the phenolic compound metabolism and scavenging ROS, thus effectively maintaining the quality of fresh-peeled CWCs while extending their shelf life.

Pallidal versus subthalamic deep-brain stimulation for meige syndrome: a retrospective study.

Deep-brain stimulation (DBS) is an effective treatment for patients with Meige syndrome. The globus pallidus interna (GPi) and the subthalamic nucleus (STN) are accepted targets for this treatment. We compared 12-month outcomes for patients who had undergone bilateral stimulation of the GPi or STN. Forty-two Asian patients with primary Meige syndrome who underwent GPi or STN neurostimulation were recruited between September 2017 and September 2019 at the Department of Neurosurgery, Peking University People's Hospital. The primary outcome was the change in motor function, including the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) at 3 days before DBS (baseline) surgery and 1, 3, 6, and 12 months after surgery. Secondary outcomes included health-related quality of life, sleep quality status, depression severity, and anxiety severity at 3 days before and 12 months after DBS surgery. Adverse events during the 12 months were also recorded. Changes in BFMDRS-M and BFMDRS-D scores at 1, 3, 6, and 12 months with DBS and without medication did not significantly differ based on the stimulation target. There were also no significant differences in the changes in health-related quality of life (36-Item Short-Form General Health Survey) and sleep quality status (Pittsburgh Sleep Quality Index) at 12 months. However, there were larger improvements in the STN than the GPi group in mean score changes on the 17-item Hamilton depression rating scale (- 3.38 vs. - 0.33 points; P = 0.014) and 14-item Hamilton anxiety rating scale (- 3.43 vs. - 0.19 points; P < 0.001). There were no significant between-group differences in the frequency or type of serious adverse events. Patients with Meige syndrome had similar improvements in motor function, quality of life and sleep after either pallidal or subthalamic stimulation. Depression and anxiety factors may reasonably be included during the selection of DBS targets for Meige syndrome.

Safety and feasibility of low-dose fluorescein-guided resection of glioblastoma.

OBJECTIVES: The extent of resection is an independent predictor of prognosis in patients with glioblastomas. Although fluorescein sodium may enhance intraoperative visualization of tumor margin and increase the extent of glioblastoma, the dose related anaphylactic reaction is still a major concern. In the present study, we used allergy skin testing to exclude the patients susceptible to anaphylaxis preoperatively, and then investigated the feasibility of low-dose fluorescein sodium to guide glioblastoma resection intraoperatively, thereby to improve the safety of fluorescein-guided glioma resection. PATIENTS AND METHODS: Patients with suspected glioblastoma based on brain MRI were subjected to allergy skin intradermal tests for fluorescein sodium preoperatively. Only those with negative allergy skin tests received intravenous injection of low dose fluorescein sodium (1-2 mg/kg) during microsurgical tumor resection under dedicated Yellow 560 filter. The degree of fluorescent staining was documented and the extent of resection was evaluated by MRI scan. RESULTS: One patient with positive allergy skin test was excluded from fluorescein sodium administration and no anaphylactic reaction was found during fluorescein sodium guided surgery in the patients who were negative for allergy skin tests. The low dose fluorescein sodium (1-2 mg/kg) could provide enough visualization of tumors with sufficient discrimination from surrounding normal brain tissue and improve the resection extent of glioblastoma. CONCLUSION: Preoperative allergy skin test is a useful method to exclude the patients susceptible to anaphylaxis, together with intraoperative low dose fluorescein sodium administration, may facilitate glioblastoma resection by fluorescence guidance while avoid safety concern of dose-related anaphylaxis.