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Scots pine (Pinus sylvestris L.) is one of the most widespread and economically important conifer species in the world. Applications like genomic selection and association studies, which could help accelerate breeding cycles, are challenging in Scots pine because of its large and repetitive genome. For this reason, genotyping tools for conifer species, and in particular for Scots pine, are commonly based on transcribed regions of the genome. In this article, we present the Axiom Psyl50K array, the first single nucleotide polymorphism (SNP) genotyping array for Scots pine based on whole-genome resequencing, that represents both genic and intergenic regions. This array was designed following a two-step procedure: first, 192 trees were sequenced, and a 430K SNP screening array was constructed. Then, 480 samples, including haploid megagametophytes, full-sib family trios, breeding population, and range-wide individuals from across Eurasia were genotyped with the screening array. The best 50K SNPs were selected based on quality, replicability, distribution across the draft genome assembly, balance between genic and intergenic regions, and genotype-environment and genotype-phenotype associations. Of the final 49 877 probes tiled in the array, 20 372 (40.84%) occur inside gene models, while the rest lie in intergenic regions. We also show that the Psyl50K array can yield enough high-confidence SNPs for genetic studies in pine species from North America and Eurasia. This new genotyping tool will be a valuable resource for high-throughput fundamental and applied research of Scots pine and other pine species.
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Pinus sylvestris , Pinus , Humanos , Pinus sylvestris/genética , Polimorfismo de Nucleótido Simple/genética , Genotipo , Fitomejoramiento , Pinus/genética , ADN IntergénicoRESUMEN
Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.
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Lagartos , Melaninas , Animales , Melaninas/genética , Lagartos/genética , Pez Cebra , Regulación de la Temperatura Corporal/genética , Pigmentación de la Piel/genética , ColorRESUMEN
Gastric cancer results in great cancer mortality worldwide, and inducing ferroptosis dramatically improves the malignant phenotypes of gastric cancer. DNA polymerase epsilon subunit 2 (POLE2) plays indispensable roles in tumorigenesis; however, its involvement and molecular basis in ferroptosis and gastric cancer are not clear. Human gastric cancer cells were infected with lentiviral vectors to knock down or overexpress POLE2, and cell ferroptosis was detected. To further validate the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4), lentiviral vectors were used. POLE2 expression was elevated in human gastric cancer cells and tissues and closely correlated with clinicopathological features in gastric cancer patients. POLE2 knockdown was induced, while POLE2 overexpression inhibited ferroptosis of human gastric cancer cells, thereby modulating the malignant phenotypes of gastric cancer. Mechanistic studies revealed that POLE2 overexpression elevated NRF2 expression and activity and subsequently activated GPX4, which then prevented lipid peroxidation and ferroptosis in human gastric cancer cells. In contrast, either NRF2 or GPX4 silence significantly prevented POLE2 overexpression-mediated inductions of cell proliferation, migration, invasion and inhibition of ferroptosis. POLE2 overexpression inhibits ferroptosis in human gastric cancer cells through activating NRF2/GPX4 pathway, and inhibiting POLE2 may be a crucial strategy to treat gastric cancer.
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Ferroptosis , Neoplasias Gástricas , Humanos , Lentivirus , Factor 2 Relacionado con NF-E2 , Nucleotidiltransferasas , Subunidades de ProteínaRESUMEN
Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. METHODS: The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. RESULTS: SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. CONCLUSIONS: SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inhibidor de Serinpeptidasas Tipo Kazal-5 , Humanos , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/metabolismo , Células HEK293 , Lipopolisacáridos , FN-kappa B/metabolismo , ARN Mensajero/metabolismo , Inhibidor de Serinpeptidasas Tipo Kazal-5/metabolismo , Receptor Toll-Like 4/metabolismoRESUMEN
Developing high electroactivity ruthenium (Ru)-based electrocatalysts for pH-universal hydrogen evolution reaction (HER) is challenging due to the strong bonding strengths of key RuâH/RuâOH intermediates and sluggish water dissociation rates on active Ru sites. Herein, a semi-ionic F-modified N-doped porous carbon implanted with ruthenium nanoclusters (Ru/FNPC) is introduced by a hydrogel sealing-pyrolying-etching strategy toward highly efficient pH-universal hydrogen generation. Benefiting from the synergistic effects between Ru nanoclusters (Ru NCs) and hierarchically F, N-codoped porous carbon support, such synthesized catalyst displays exceptional HER reactivity and durability at all pH levels. The optimal 8Ru/FNPC affords ultralow overpotentials of 17.8, 71.2, and 53.8 mV at the current density of 10 mA cm-2 in alkaline, neutral, and acidic media, respectively. Density functional theory (DFT) calculations elucidate that the F-doped substrate to support Ru NCs weakens the adsorption energies of H and OH on Ru sites and reduces the energy barriers of elementary steps for HER, thus enhancing the intrinsic activity of Ru sites and accelerating the HER kinetics. This work provides new perspectives for the design of advanced electrocatalysts by porous carbon substrate implanted with ultrafine metal NCs for energy conversion applications.
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To explore novel electrode materials with in-depth elucidation of initial coulombic efficiency (ICE), kinetics, and charge storage mechanisms is of great challenge for Na-ion storage. Herein, a novel 3D antiperovskite carbide Ni3ZnC0.7@rGO anode coupled with ether-based electrolyte is reported for fast Na-ion storage, exhibiting superior performance than ester-based electrolyte. Electrochemical tests and density functional theory (DFT) calculations show that Ni3ZnC0.7@rGO anode with ether-based electrolyte can promote charge/ion transport and lower Na+ diffusion energy barrier, thereby improving ICE, reversible capacity, rate, and cycling performance. Cross-sectional-morphology and depth profiling surface chemistry demonstrate that not only a thinner and more homogeneous reaction interface layer with less side effects but also a superior solid electrolyte interface (SEI) film with a high proportion of inorganic components are formed in the ether-based electrolyte, which accelerates Na+ transport and is the significant reason for the improvement of ICE and other electrochemical properties. Meanwhile, electrochemical and ex situ measurements have revealed conversion, alloying, and co-intercalation hybrid mechanisms of the Ni3ZnC0.7@rGO anode based on ether electrolyte. Interestingly, the Na-ion capacitors (SICs) designed by pairing with activated carbon (AC) cathode exhibit favorable electrochemical performance. Overall, this work provides deep insights on developing advanced materials for fast Na-ion storage.
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A frozen-temperature (below -28 °C) laser tuning way is developed to optimize metal halide perovskite (MHP)'s stability and opto-electronic properties, for emitter, photovoltaic and detector applications. Here freezing can adjust the competitive laser irradiation effects between damaging and annealing/repairing. And the ligand shells on MHP surface, which are widely present for many MHP materials, can be frozen and act as transparent solid templates for MHP's re-crystallization/re-growth during the laser tuning. With model samples of different types of CsPbBr3 nanocube arrays,an attempt is made to turn the dominant exposure facet from low-energy [100] facet to high-energy [111], [-211], [113] and [210] ones respectively; selectively removing the surface impurities and defects of CsPbBr3 nanocubes to enhance the irradiation durability by 101 times; and quickly (tens of seconds) modifying a Ruddlesden-Popper (RP) boundary into another type of boundary like twinning, and so on. The laser tuning mechanism is revealed by an innovative in situ cryo-transmission electron microscope (cryo-TEM) exploration at atomic resolution.
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BACKGROUND: Circular RNAs (circRNAs), which are a new type of single-stranded circular RNA, have significant involvement in progression of many diseases, including tumors. Currently, multiple circRNAs have been identified in hepatocellular carcinoma (HCC). Our study aims to investigate the function and mechanism of circDCAF8 in HCC. METHODS: The expression of circDCAF8 (hsa_circ_0014879) in HCC and para-carcinoma tissue samples was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The biological function of circDCAF8 in HCC was confirmed by experiments conducted both in vitro and in vivo. And the relationship between circDCAF8, miR-217 and NAP1L1 was predicted by database and verified using qRT-PCR, RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Exosomes isolated from HCC cells were utilized to assess the connection of exosomal circDCAF8 with HCC angiogenesis and regorafenib resistance. RESULTS: CircDCAF8 is upregulated in HCC tissues and cell lines, and is linked to an unfavourable prognosis for HCC patients. Functionally, circDCAF8 was proved to facilitate proliferation, migration, invasion and Epithelial-Mesenchymal Transformation (EMT) in HCC cells. Animal examinations also validated the tumor-promoting characteristics of circDCAF8 on HCC. Besides, exosomal circDCAF8 promoted angiogenesis in HUVECs. Mechanistically, circDCAF8 interacted with miR-217 and NAP1L1 was a downstream protein of miR-217. CircDCAF8 promoted NAP1L1 expression by sponging miR-217. In addition, exosomes may transfer circDCAF8 from regorafenib-resistant HCC cells to sensitive cells, where it would confer a resistant phenotype. CONCLUSION: CircDCAF8 facilitates HCC proliferation and metastasis via the miR-217/NAP1L1 axis. Meanwhile, circDCAF8 can promote angiogenesis and drive resistance to regorafenib, making it a viable therapeutic target for HCC patients.
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Carcinoma Hepatocelular , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Exosomas , Neoplasias Hepáticas , MicroARNs , Neovascularización Patológica , Compuestos de Fenilurea , Piridinas , ARN Circular , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Exosomas/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Resistencia a Antineoplásicos/genética , Neovascularización Patológica/genética , Animales , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Línea Celular Tumoral , Piridinas/farmacología , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Masculino , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Ratones , Ratones Endogámicos BALB C , Femenino , Secuencia de Bases , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Persona de Mediana Edad , AngiogénesisRESUMEN
PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.
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The thermodynamically stable 2H-phase MoS2 is a brilliant material toward hydrogen evolution reaction (HER) owing to its excellent Gibbs free energy of hydrogen adsorption. Nevertheless, the poor intrinsic properties of 2H-MoS2 limit its electrocatalytic performances toward HER. In this work, graphitic carbon nitride covalently bridging 2H-MoS2 (MoS2/GCN) is proposed to construct robust HER electrocatalysts. The strong π-p electron coupling between the delocalized π electrons of GCN and the localized p electrons of S atoms sufficiently expose active sites and accelerate the reaction kinetics. To be specific, MoS2/GCN exhibits remarkable HER activity (160 mV at 10 mA·cm-2) and long-term durability. Importantly, MoS2/GCN also provides great potential for industrial application. Density functional theory (DFT) calculations disclose that the π-p electron coupling at the MoS2/GCN interface regulates the electronic structure of S atoms, consequently providing enhanced HER performance. This work presents a feasible pathway to develop advanced electrocatalysts for energy conversions.
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The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from â¼88 to 100%. Reducing substances consumed ABTSâ¢+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Phâ¢), promoting the transformation of Fe(VI) â Fe(V) â Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTSâ¢+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.
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Electrones , Oxidación-Reducción , Hierro/química , Compuestos Orgánicos/química , Benzotiazoles/química , Ácidos SulfónicosRESUMEN
The key to the resource recycling of saline wastes in form of polyhydroxyalkanoates (PHA) is to enrich mixed cultures with salt tolerance and PHA synthesis ability. However, the comparison of saline sludge from different sources and the salt tolerance mechanisms of salt-tolerant PHA producers need to be clarified. In this study, three kinds of activated sludge from different salinity environments were selected as the inoculum to enrich salt-tolerant PHA producers under aerobic dynamic feeding (ADF) mode with butyric acid dominated mixed volatile fatty acid as the substrate. The maximum PHA content (PHAm) reached 0.62 ± 0.01, 0.62 ± 0.02, and 0.55 ± 0.03 g PHA/g VSS at salinity of 0.5%, 0.8%, and 1.8%, respectively. Microbial community analysis indicated that Thauera, Paracoccus, and Prosthecobacter were dominant salt-tolerant PHA producers at low salinity, Thauera, NS9_marine, and SM1A02 were dominant salt-tolerant PHA producers at high salinity. High salinity and ADF mode had synergistic effects on selection and enrichment of salt-tolerant PHA producers. Combined correlation network with redundancy analysis indicated that trehalose synthesis genes and betaine related genes had positive correlation with PHAm, while extracellular polymeric substances (EPS) content had negative correlation with PHAm. The compatible solutes accumulation and EPS secretion were the main salt tolerance mechanisms of the PHA producers. Therefore, adding compatible solutes is an effective strategy to improve PHA synthesis in saline environment.
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Polihidroxialcanoatos , Salinidad , Tolerancia a la Sal , Polihidroxialcanoatos/biosíntesis , Polihidroxialcanoatos/metabolismo , Aguas del Alcantarillado/microbiología , Bacterias/metabolismoRESUMEN
Alkaline pre-treatment is known to enhance the acid production efficiency of sludge but adversely affects its dewatering performance. In this study, the improvement of sludge dewaterability by a novel bioleaching system with inoculating domesticated acidified sludge (AS) and its underlying mechanism were investigated. The results showed that although the addition of Fe2+ and the reduction of pH improved the dewatering performance of sludge, their effects were inferior to that of AS + Fe. The addition of AS and Fe2+ significantly reduced the specific resistance to filtration and capillary suction time of the sludge by 98.6 % and 95.5 %, respectively. This improvement in dewatering performance was achieved through the combined actions of bio-acidification, bio-oxidation, and bio-flocculation. Remarkably, under alkaline pH, microorganisms in AS remained active, leading to the formation of iron-based bioflocculants, along with a rapid pH decrease. These bioflocculants, in combination with protein (PN) in tightly bound extracellular polymeric substances (TB-EPS) through amide bonding, transformed TB-EPS from extractable to non-extractable form, reducing PN content from 12.1 mg g-1DS to 5.09 mg g-1DS and altering the protein's secondary structure. Consequently, the gel-like TB-EPS matrix effectively broke down, releasing cellular water and significantly enhancing sludge dewaterability.
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Aguas del Alcantarillado , Agua , Agua/química , Hierro/química , Filtración , Oxidación-Reducción , Eliminación de Residuos Líquidos/métodosRESUMEN
MnBi2Te4 can generate a variety of exotic topological quantum states, which are closely related to its special structure. We conduct comprehensive multiple-cycle high-pressure research on MnBi2Te4 by using a diamond anvil cell to study its phase transition behaviors under high pressure. As observed, when the pressure does not exceed 15 GPa, the material undergoes an irreversible metal-semiconductor-metal transition, whereas when the pressure exceeds 17 GPa, the layered structure is damaged and becomes irreversibly amorphous due to the lattice distortion caused by compression, but it is not completely amorphous, which presents some nano-sized grains after decompression. Our investigation vividly reveals the phase transition behaviors of MnBi2Te4 under high pressure cycling and paves the experimental way to find topological phases under high pressure.
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Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy.
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Ferroptosis , Nanopartículas , Neoplasias , Humanos , Piroptosis , Inmunoterapia , Autofagia , Inhibidores de Puntos de Control Inmunológico , Neoplasias/terapiaRESUMEN
STUDY OBJECTIVES: Artificial intelligence (AI) is quickly advancing in the field of sleep medicine, which bodes well for the potential of actual clinical use. In this study, an analysis of the 2nd China Intelligent Sleep Staging Competition was conducted to gain insights into the general level and constraints of AI-assisted sleep staging in China. METHODS: The outcomes of 10 teams from the children's track and 13 teams from the adult track were investigated in this study. The analysis included overall performance, differences between five different sleep stages, variations across subjects, and performance during stage transitions. RESULTS: The adult track's accuracy peaked at 80.46%, while the children's track's accuracy peaked at 88.96%. On average, accuracy rates stood at 71.43% for children and 68.40% for adults. All results were produced within a mere 5-min timeframe. The N1 stage was prone to misclassification as W, N2, and R stages. In the adult track, significant differences were apparent among subjects (p < 0.05), whereas in the children's track, such differences were not observed. Nonetheless, both tracks experienced a performance decline during stage transitions. CONCLUSIONS: The computational speed of AI is remarkably fast, simultaneously holding the potential to surpass the accuracy of physicians. Improving the machine learning model's classification of the N1 stage and transitional periods between stages, along with bolstering its robustness to individual subject variations, is imperative for maximizing its ability in assisting clinical scoring.
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Fases del Sueño , Humanos , China , Fases del Sueño/fisiología , Adulto , Niño , Masculino , Inteligencia Artificial , Femenino , PolisomnografíaRESUMEN
BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.
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Desplazamiento del Disco Intervertebral , Personal Militar , Fusión Vertebral , Espondilolistesis , Humanos , Desplazamiento del Disco Intervertebral/epidemiología , Desplazamiento del Disco Intervertebral/cirugía , Espondilolistesis/epidemiología , Espondilolistesis/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Vértebras Lumbares/cirugía , China/epidemiología , Fusión Vertebral/métodosRESUMEN
Objective: As the reform of China's medical and healthcare system progresses and the demand for medical and healthcare services increases, the humanistic quality of medical personnel has received more attention and concern. The humanistic quality of medicine for medical staff is specifically translated into the ethics of nursing for nursing staff. In this study, we explored the effectiveness of the education model based on "moral and medical integration" in the nursing students' education in the operating room. Methods: The "moral and medical integration" education model was implemented in The Affiliated Changzhou No. 2 People's Hospital since September 1, 2021, and 50 nursing students who received the traditional education model before the implementation from May 1, 2021, to August 31, 2021, were selected as the control group. The study group was composed of 50 nursing trainees who received the traditional education model from 1 September 2021 to 30 November 2021 and 50 nursing trainees who received the education model based on the "integration of moral and medical science". The nursing theory and nursing skills scores, professional nursing practice scores, moral courage scores, and satisfaction with teaching were compared between the two groups. Results: The nursing theory scores (t = 14.36, P < .001), nursing skills scores (t = 11.27, P < .001), and teaching satisfaction of the study group (t = 4.76, P < .029) were all higher than those of the control group . After the education, all the professional nursing practice ability scores(t=9.16, P < .001; t = 12.24, P < .001; t = 10.42, P < .001; t = 10.95, P < .001) and moral courage scores(t=7.81, P < .001; t = 11.76, P < 0.001; t = 15.11, P < .001; t = 12.24, P < .001) of the study group were higher than those of the control group (P < .05). Conclusion: The education model based on "moral and medical integration" can help improve the professional nursing level of nursing students in the operating theatre.
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OBJECTIVES: The objective was to explore the association between serum copper levels and the prevalence of stroke. METHODS: Data were obtained from 3 consecutive National Health and Nutrition Examination Survey (NHANES) cycles (2011-2016). Weighted multivariable logistic regression analysis was conducted to evaluate the association between serum copper levels and self-reported stroke. RESULTS: A total of 5,151 adults met the inclusion criteria. A total of 181 (3.51%) stroke patients were identified. In comparison to individuals with serum copper levels in the lowest tertile (<16.4 µmol/l), those with levels in the middle tertile (16.4-19.8 µmol/l) had an odds ratio (OR) of 0.99 (95% confidence interval [CI]: 0.44-2.25), while those with levels in the highest tertile (>19.8 µmol/l) had an OR of 2.36 (95% CI: 1.01-5.52). Furthermore, each standard deviation (SD) increase in serum copper was found to be positively associated with the prevalence of stroke, with an OR of 1.44 (95% CI: 1.11-1.86). Doseâresponse analysis showed a positive linear association between serum copper levels and stroke (Pnonlinearity=0.554). CONCLUSIONS: This cross-sectional study suggested a positive association between serum copper levels and stroke among American adults.