Reversal of Obesity by Enhancing Slow-wave Sleep via a Prokineticin Receptor Neural Circuit.

Obese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and exacerbates diet-induced obesity (DIO). However, the neural circuit and signaling mechanism underlying the reciprocal control of appetite and sleep is yet not elucidated. Here, we report a neural circuit where prokineticin receptor 2 (PROKR2)-expressing neurons within the parabrachial nucleus (PBN) of the brainstem received direct projections from neuropeptide Y receptor Y2 (NPY2R)-expressing neurons within the lateral preoptic area (LPO) of the hypothalamus. The RNA-Seq results revealed Prokr2 in the PBN is the most regulated GPCR signaling gene that is responsible for comorbidity of obesity and sleep dysfunction. Furthermore, those NPY2R LPO neurons are minimally active during NREM sleep and maximally active during wakefulness and REM sleep. Activation of the NPY2R LPO →PBN circuit or the postsynaptic PROKR2 PBN neurons suppressed feeding of a high-fat diet and abrogated morbid sleep patterns in DIO mice. Further studies showed that genetic ablation of the PROKR2 signaling within PROKR2 PBN neurons alleviated the hyperphagia and weight gain, and restored sleep dysfunction in DIO mice. We further discovered pterostilbene, a plant-derived stilbenoid, is a powerful anti-obesity and sleep-improving agent, robustly suppressed hyperphagia and promoted reconstruction of a healthier sleep architecture, thereby leading to significant weight loss. Collectively, our results unveil a neural mechanism for the reciprocal control of appetite and sleep, through which pterostilbene, along with a class of similarly structured compounds, may be developed as effective therapeutics for tackling obesity and sleep disorders.

Exploring the dynamic behaviors of five pesticides in lettuce: Implications for consumer health through field and modeling experiments.

Lettuce, a globally consumed nutritious vegetable, is often linked to concerns regarding pesticide residues. To address this issue, we conducted field trials and utilized dynamiCROP modeling to examine the uptake, distribution, translocation, and dissipation of five pesticides (λ-cyhalothrin, difenoconazole, acetamiprid, dimethomorph, and ß-cypermethrin) commonly detected in lettuce. At harvest, pesticides residues were below the maximum residue limits (MRLs) at 0.05, 0.39, 0.047, 0.72, and 0.072 mg kg-1, respectively. Simulation results elucidated distinct behaviors of the pesticides following application to lettuce foliage across various compartments. However, all pesticides exhibited a common dissipation trend, initially stabilizing or increasing before gradually declining. For all five pesticides, the largest contribution of residues on lettuce leaves came from the leaf surface during the early period after application, and from the soil in the long term. Health risk assessments indicated negligible risks associated with consuming lettuce containing these pesticides, both in the short and long term.

Wild-type IDH2 is a therapeutic target for triple-negative breast cancer.

Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

Photoelectric dual-mode triggered phase change materials for all-weather personal thermal management and shape memory.

To cope with the demand of more complex and variable applications, it is urgent to develop dual-mode triggered, breathable, and shape-memory wearable heaters for all-weather personal thermal management of composite phase change materials (PCMs). Herein, after high-temperature carbonization of ZnCo-MOF (metal-organic framework) nanosheet array grown in situ on flexible and breathable carbon cloth (CC) and subsequent encapsulation of polyethylene glycol (PEG), the as-prepared PEG/CC@Co/CNT (carbon nanotube) composite PCMs exhibited good breathability, mechanical strength (tensile strength of 9.15 MPa), thermal energy storage density (114.19 J/g), and shape memory due to the synergy of flexible CC skeleton and rigid PEG. More importantly, composite PCMs possessed excellent solar-thermal (93.7 %, 100 mW/cm2) and electro-thermals (94.5 %, 2.0 V) conversion and storage capacity, benefiting from the conjugation effect of high graphitized carbon/carbon heterostructure with fast electron/photon/phonon transmission and the localized surface plasmon resonance effect of Co nanoparticles. Therefore, the integration of solar heating and Joule heating into breathable composite PCMs can be accurately used for next-generation all-weather, all-season, dual-mode triggered personal thermal management, including indoor/outdoor, daytime/night, rainy/cloudy and other complex and changeable scenarios.

Personalized Music Therapy for Elderly Patients with Chronic Renal Failure to Improve their Quality of Life and Mental Health: A Retrospective Study.

BACKGROUND: Chronic renal failure (CRF) poses significant clinical risks. Therefore, attention should be paid to the daily nursing of such patients, and better clinical nursing programs should be provided. METHODS: The data of 120 patients with CRF at Yantai Yuhuangding Hospital from March 2020 to March 2022 were retrospectively analyzed. After 8 patients were excluded, 112 patients were finally included in this study. The included patients were divided into group A (58 patients receiving clinical routine nursing) and group B (54 patients receiving clinical routine nursing and personalized music) according to different nursing schemes. The anxiety level, depression level, quality of life (QOL), and clinical satisfaction of the patients in both groups were compared before and after nursing. RESULTS: Before the implementation of nursing, no significant difference existed in the levels of anxiety, depression, and QOL between the two groups (P > 0.05). After nursing, group B had significantly lower levels of anxiety and depression and significantly higher QOL than group A (P < 0.001). No significant difference in clinical nursing satisfaction was found between the two groups (P > 0.05). CONCLUSION: The implementation of personalized music can improve the QOL and psychological states of patients, with clinical application value.

Synchronous removal of gaseous toluene and benzene and degradation process shifts in microbial fuel cell-biotrickling filter system.

Illustrating the biodegradation processes of multi-component volatile organic compounds (VOCs) will expedite the implication of biotechnology in purifying industrial exhaust. Here, performance shifts of microbial fuel cell and biotrickling filter combined system (MFC-BTF) are investigated for removing single and dual components of toluene and benzene. Synchronous removal of toluene (95 %) and benzene (97 %) are achieved by MFC-BTF accompanied with the output current of 0.41 mA. Elevated content of extracellular polymeric substance facilitates the mass transfer of benzene with the presence of toluene. Strains of Bacteroidota, Proteobacteria and Chloroflexi contribute to the removal of dual components VOCs. Empty bed reaction time and the VOCs concentration are the important factors influencing their dissolution in the system. The biodegradation of toluene and benzene proceeds with 2-hydroxymuconic semialdehyde and o-hydroxybenzoic acid as the main intermediates. These results provide a comprehensive understanding of multi-component VOCs removal by MFC-BTF and guide the system design, optimization, and scale-up.

Research on helmet wearing detection method based on deep learning.

The vigorous development of the construction industry has also brought unprecedented safety risks. The wearing of safety helmets at the construction site can effectively reduce casualties. As a result, this paper suggests employing a deep learning-based approach for the real-time detection of safety helmet usage among construction workers. Based on the selected YOLOv5s network through experiments, this paper analyzes its training results. Considering its poor detection effect on small objects and occluded objects. Therefore, multiple attention mechanisms are used to improve the YOLOv5s network, the feature pyramid network is improved into a BiFPN bidirectional feature pyramid network, and the post-processing method NMS is improved into Soft-NMS. Based on the above-improved method, the loss function is improved to enhance the convergence speed of the model and improve the detection speed. We propose a network model called BiFEL-YOLOv5s, which combines the BiFPN network and Focal-EIoU Loss to improve YOLOv5s. The average precision of the model is increased by 0.9% the recall rate is increased by 2.8%, and the detection speed of the model does not decrease too much. It is better suited for real-time safety helmet object detection, addressing the requirements of helmet detection across various work scenarios.

Development of an immune-related diagnostic predictive model for oral lichen planus.

Oral lichen planus (OLP) was a chronic inflammatory disease of unknown etiology with a 1.4% chance of progressing to malignancy. However, it has been suggested in several studies that immune system disorders played a dominant role in the onset and progression of OLP. Therefore, this experiment aimed to develop a diagnostic prediction model for OLP based on immunopathogenesis to achieve early diagnosis and treatment and prevent cancer. In this study, 2 publicly available OLP datasets from the gene expression omnibus database were filtered. In the experimental group (GSE52130), the level of immune cell infiltration was assessed using MCPcounter and ssGSEA algorithms. Subsequently, differential expression analysis and gene set enrichment analysis were performed between the OLP and control groups. The resulting differentially expressed genes were intersected with immunologically relevant genes provided on the immunology database and analysis portal database (ImmPort) website to obtain differentially expressed immunologically relevant genes (DEIRGs). Furthermore, the gene ontology and kyoto encyclopedia of genes and genomes analyses were carried out. Finally, protein-protein interaction network and least absolute shrinkage and selection operator regression analyses constructed a model for OLP. Receiver operating characteristic curves for the experimental and validation datasets (GSE38616) were plotted separately to validate the model's credibility. In addition, real-time quantitative PCR experiment was performed to verify the expression level of the diagnostic genes. Immune cell infiltration analysis revealed a more significant degree of inflammatory infiltration in the OLP group compared to the control group. In addition, the gene set enrichment analysis results were mainly associated with keratinization, antibacterial and immune responses, etc. A total of 774 differentially expressed genes was obtained according to the screening criteria, of which 65 were differentially expressed immunologically relevant genes. Ultimately, an immune-related diagnostic prediction model for OLP, which was composed of 5 hub genes (BST2, RNASEL, PI3, DEFB4A, CX3CL1), was identified. The verification results showed that the model has good diagnostic ability. There was a significant correlation between the 5 hub diagnostic biomarkers and immune infiltrating cells. The development of this model gave a novel insight into the early diagnosis of OLP.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Effects of digital game-based learning on students' digital etiquette literacy, learning motivations, and engagement.

Recent years have seen a substantial rise in the number of children and teenagers surfing the Internet; however, not all use this resource responsibly. Digital etiquette, a core element of digital citizenship, contributes to proper Internet adoption and reduces inappropriate behavior in cyberspace. To protect children and teenagers from harm online, it is essential to familiarize them with digital etiquette literacy and codes of Internet conduct from an early age. Digital citizenship education is relatively rare in Chinese primary schools. Research on student performance in this regard is also lacking. Digital game-based learning (DGBL) has demonstrated potential to enhance students' learning, motivations, and engagement. In this paper, we designed and implemented a digital game-based course intended to foster students' digital etiquette literacy. A quasi-experiment in a primary school in Guangzhou revealed that compared with conventional learning, DGBL improved students' digital etiquette literacy while positively influencing their learning-related motivations and engagement. This study can serve as a reference for primary or secondary schools interested in teaching digital etiquette to support global digital citizenship education.

In-Situ Derived Defective Ru Particles Anchored on Ru-Ni Layered Double Hydroxides for Enhanced Alkaline Hydrogen Evolution.

Developing active, stable, and cost-efficient electrocatalysts to replace platinum for the alkaline hydrogen evolution reaction (HER) is highly desirable yet represents a great challenge. Here, it is reported on a facile one-pot synthesis of Rux Ni layered double hydroxides (Rux Ni-LDHs) that exhibit remarkable HER activity and stability after an in-situ activation treatment, surpassing most state-of-the-art Ru-based catalysts as well as commercial Ru/C and Pt/C catalysts. The structural and chemical changes triggered by in-situ activation are systematically investigated, and the results clearly show that the pristine, less-active Rux Ni-LDHs are transformed into a highly active catalyst characterized by raft-like, defect-rich Ru° particles decorated on the surface of Rux Ni-LDHs. Density functional theory (DFT) calculations reveal that the defective Ru sites can effectively optimize the reaction pathway and lower the free energies of the elemental steps involved, leading to enhanced intrinsic activity. This work highlights the importance of the currently understudied strategy of defect engineering in boosting the HER activity of Ru-based catalysts and offers an effective approach involving in-situ electrochemical activation for the development of high-performance alkaline HER catalysts.

Global miRNA profiling reveals key molecules that contribute to different chronic lymphocytic leukemia incidences in Asian and Western populations.

It has been known for decades that the incidence of chronic lymphocytic leukemia (CLL) is significantly lower in Asia than in Western countries, but the reason responsible for this difference still remains a major knowledge gap. Using GeneChip® miRNA array to analyze the global microRNA expression in B lymphocytes from Asian and Western CLL patients and healthy individuals, we have identified microRNA with CLL-promoting or suppressive functions that are differentially expressed in Asian and Western individuals. In particular, miR-4485 is upregulated in CLL patients of both ethnic groups, and its expression is significantly lower in Asian healthy individuals. Genetic silencing of miR-4485 in CLL cells suppresses leukemia cell growth, whereas ectopic expression of miR-4485 promotes cell proliferation. Mechanistically, miR-4485 exerts its CLL-promoting activity by inhibiting the expression of TGR5 and activating the ERK1/2 pathway. In contrast, miR-138, miR-181a, miR- 181c, miR-181d, and miR-363 with tumor-suppressive function are highly expressed in Asian healthy individuals. Our study suggests that differential expression of several important microRNA with pro- or anti-CLL functions in Asian and Western B lymphocytes likely contributes to the difference in CLL incidence between the two ethnic groups, and that miR-4485 and its downstream molecule TGR5 could be potential therapeutic targets.

Quercetin targets SarA of methicillin-resistant Staphylococcus aureus to mitigate biofilm formation.

IMPORTANCE: Anti-biofilm is an important strategy against Staphylococcus aureus chronic infection. SarA is a positive regulator of biofilm formation in S. aureus. In this study, we identified the SarA inhibitor quercetin using computer simulation screening. Previous studies have shown that quercetin inhibits biofilm; however, the underlying mechanism remains unknown. This study revealed the inhibitory effect of quercetin on the SarA protein. We also isolated the SarA protein and confirmed its interaction with quercetin in vitro. Besides, the inhibitory effect of quercetin on the transcription and translation levels of the SarA protein was also determined. The effects of quercetin on S. aureus biofilm inhibition and biofilm components were consistent with the changes in the transcription level of biofilm-related genes regulated by SarA. In summary, our study revealed the mechanism by which quercetin affects biofilm formation by inhibiting the transcriptional regulator SarA of S. aureus.

Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship.

INTRODUCTION: This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs). METHODS: A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses. RESULTS: The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042). CONCLUSION: The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.

Autotrophic denitrification based on sulfur-iron minerals: advanced wastewater treatment technology with simultaneous nitrogen and phosphorus removal.

Autotrophic denitrification technology has many advantages, including no external carbon source addition, low sludge production, high operating cost efficiency, prevention of secondary sewage pollution, and stable treatment efficiency. At present, the main research on autotrophic denitrification electron donors mainly includes sulfur, iron, and hydrogen. In these autotrophic denitrification systems, pyrite has received attention due to its advantages of easy availability of raw materials, low cost, and pH stability. When pyrite is used as a substrate for autotropic denitrification, sulfide (S2-) and ferrous ion (Fe2+) in the substrate will provide electrons to convert nitrate (NO3-) in sewage first to nitrite (NO2-), then to nitrogen (N2), and finally to discharge the system. At the same time, sulfide (S2-) loses electrons to sulfate (SO42-) and ferrous ion (Fe2+) loses electrons to ferric iron (Fe3+). Phosphates (PO43-) in wastewater are chemically combined with ferric iron (Fe3+) to form ferric phosphate (FePO4) precipitate. This paper aims to provide a detailed and comprehensive overview of the dynamic changes of nitrogen (N), phosphorus (P), and other substances in the process of sulfur autotrophic denitrification using iron sulfide, and to summarize the factors that affect wastewater treatment in the system. This work will provide a relevant research direction and theoretical basis for the field of sulfur autotrophic denitrification, especially for the related experiments of the reaction conversion of various substances in the system.

A Study of Pigment, Adhesive, and Firing Temperature in Pottery Figurines Excavated from the Tomb of Qibi Ming, China.

Some painted pottery figurines were excavated from the tomb of Qibi Ming of the Tang Dynasty. A series of analytical techniques were employed to understand the craftsmanship of these painted pottery figurines. The pigment, cross-section, adhesive, and firing temperature were analyzed using microscopy (OM), energy X-ray fluorescence spectrometry (EDX), micro-Raman spectroscopy, pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS), and a dilatometer (DIL). The results demonstrated that the surface of the pigment layers had degraded to different degrees. The pigment particles were litharge, gypsum, malachite, cinnabar, hematite, minium, white lead, and carbon black. The cross-sectional images show that the painted layer of figurines 10-0966 and 10-0678 included a pigment layer and a preparation layer. The preparation layer of both pigments was lead white. Animal glue was used as an adhesive. The firing temperature of the pottery figurines was likely 1080 °C. This study can provide more accurate information with regard to the composition of the raw materials utilized in the making of these artifacts and support the selection of appropriate substances for the purposes of conservation and restoration of the painted pottery figurines.

Carbon Encapsulation of Supported Metallic Iridium Nanoparticles: An in Situ Transmission Electron Microscopy Study and Implications for Hydrogen Evolution Reaction.

Carbon-supported metal nanoparticles (NPs) comprise an important class of heterogeneous catalysts. The interaction between the metal and carbon support influences the overall material properties, viz., the catalytic performance. Herein we use in situ and ex situ transmission electron microscopy (TEM) in combination with in situ X-ray spectroscopy (XPS) to investigate the encapsulation of metallic iridium NPs by carbon in an Ir/C catalyst. Real-time atomic-scale imaging visualizes particle reshaping and increased graphitization of the carbon support upon heating of Ir/C in vacuum. According to in situ TEM results, carbon overcoating grows over Ir NPs during the heating process, starting from ca. 550 °C. With the carbon overlayers formed, no sintering and migration of Ir NPs is observed at 800 °C, yet the initial Ir NPs sinter at or below 550 °C, i.e., at a temperature associated with an incomplete particle encapsulation. The carbon overlayer corrugates when the temperature is decreased from 800 to 200 °C and this process is associated with the particle surface reconstruction and is reversible, such that the corrugated carbon overlayer can be smoothed out by increasing the temperature back to 800 °C. The catalytic performance (activity and stability) of the encapsulated Ir NPs in the hydrogen evolution reaction (HER) is higher than that of the initial (nonencapsulated) state of Ir/C. Overall, this work highlights microscopic details of the currently understudied phenomenon of the carbon encapsulation of supported noble metal NPs and demonstrates additionally that the encapsulation by carbon is an effective measure for tuning the catalytic performance.