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Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8+ T cells and the prognosis of AML patients. To develop a CD8+ T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8+ T cells in bulk RNA-seq and found it significantly correlated with observed singlecell RNA sequencing data and the proportions of CD8+ T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8+ THigh and CD8+ TLow groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8+ T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML. [ABSTRACT FROM AUTHOR]

Many parameters and complex boundaries are involved in the spatial arrangement of an underground powerhouse in a hydropower station, necessitating referencing many relevant cases and specifications. However, in practical applications, retrieving such cases or specifications is difficult, and there is a lack of knowledge regarding cascading logic among design parameters. To address this issue, this study proposes a novel methodology for constructing a targeted knowledge graph, in this case, a knowledge graph for building information modeling (BIM) for underground powerhouses in hydropower plants. Subsequently, based on this knowledge graph, this study develops a question-and-answer (Q&A) system to facilitate subsequent applications. First, the ontology skeleton of the spatial arrangement design of an underground powerhouse in a hydropower station, that represents the knowledge organization structure of the knowledge graph, is constructed by carefully analyzing the requirements for intelligent modeling of underground powerhouses. A large volume of unstructured data is identified based on the optical character recognition (OCR) technology; the collected data are divided into words to extract correlation knowledge using THU Lexical Analyzer for Chinese (THULAC). Subsequently, the knowledge triad of the spatial arrangement of the underground powerhouse is extracted based on ChatGPT and stored in Neo4j, a knowledge base, to build a knowledge graph. Finally, the knowledge graph is employed to realize the query of knowledge and parameter recommendation to assist the digital intelligent design of the spatial arrangement of an underground powerhouse in a pumped storage hydropower station. [ABSTRACT FROM AUTHOR]

Olfaction, the sense of smell, is crucial for animal survival, especially in localizing prey or food. However, little is known about the fish behavioral responses to specific food odors and which olfactory receptor might be activated by the food odors. Here, we examined the evolutionary relationships and classified the subfamilies of olfactory receptors (ORs), and conducted behavioral and gene expression analysis in grass carp (Ctenopharyngodon idellus). We identified 196 intact ORs in the grass carp genome and classified them into 8 subfamilies: β, δ, ε, η, γ, κ, θ, and ζ. 12 representative ORs (4 β, 4 δ, and 4 ε) were highly expressed in the olfactory epithelium (OE) of 24-monthold grass carp. Behavioral exploration found that grass carp showed different behaviors to different food odors at a series of concentrations. Specifically, 0.01 μmol/L amino acid mixtures and 0.005 x Hydrilla verticillata extracts strongly changed the preference index and swimming trajectories in 6-month-old grass carp. In addition, the two food odors stimulation differentially induced ORs expression in three tissues, especially strong in the olfactory bulb and brain. Altogether, our results suggest that olfaction plays an important role in the regulation of fish feeding behavior and provide a basis for further studies on the function and specific recognition of olfactory receptors in fish. [ABSTRACT FROM AUTHOR]

Osteosarcoma stands as the most prevalent bone tumor, characterized by a heightened tendency for local recurrence and distant metastasis, resulting in a bleak prognosis. Presently, there exists a shortage of novel markers to effectively determine the prognosis of osteosarcoma patients. Recent research indicates that hematological markers partially mirror an individual's microenvironment, offering potential insights into predicting patient prognosis. However, prior studies predominantly focused on the prognostic significance of singular hematological indices, failing to comprehensively represent the tumor microenvironment of patients. In our investigation, we meticulously gathered data on 22 hematological and electrolyte markers, utilizing LASSO Cox regression analysis to devise an Electrolyte Prognostic Scoring System (EPSS). The EPSS encompasses various indicators, including immunity, inflammation, coagulation, and electrolyte levels. Our findings indicate that the EPSS stands as an independent prognostic factor for overall survival among osteosarcoma patients. It serves as a valuable addition to clinical characteristics, adept at discerning high-risk patients from those deemed clinically low-risk. Furthermore, EPSS-based nomograms demonstrate commendable predictive capabilities. [ABSTRACT FROM AUTHOR]

The objective of this study was to enhance the membrane permeability and anticancer effectiveness of (20S)-protopanaxadiol (PPD) by introducing triphenylphosphonium into the OH group at the C-3 site. This study shows that the anti-proliferation activity of CTPPPPD, with an IC50 value of 1.65 ± 0.10 μmol/L, was 33-times better than that of PPD (with an IC50 value of 54.56 ± 4.56 μmol/L) and superior to that of cisplatin (with an IC50 value of 1.82 ± 0.25 μmol/L) against A549 cells. Biological examinations suggested that CTPPPPD treatment reduced the growth rate of A549 cells, increased the permeability of cell membranes, and changed the structure of chromosomal DNA in a concentration-dependent manner. Annexin V/PI assay and flow cytometry were employed to detect the effect of CTPPPPD on the apoptosis of A549 cells. The results showed that CTPPPPD could induce the apoptosis of A549 cells, and the apoptosis rate of A549 cells treated with 0, 1.0, 2.0, and 4.0 μM of CTPPPPD for 24 h was 0%, 4.9%, 12.7%, and 31.0%, respectively. The integration of transcriptomics and metabolomics provided a systematic and detailed perspective on the induced antitumor mechanisms. A combined analysis of DEGs and DAMs suggested that they were primarily involved in the central carbon metabolism pathway in cancer, as well as the metabolism of aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate. Central carbon metabolism in cancer-related genes, i.e., SLC16A3, FGFR3, LDHA, PGAM1, and SLC2A1, significantly reduced after treatment with CTPPPPD. In particular, the dominant mechanism responsible for total antitumor activity may be attributed to perturbations in the PI3K-AKT, MAPK, and P53 pathways. The findings derived from transcriptomics and metabolomics were empirically confirmed through q-PCR and molecular docking. Further analyses revealed that CTPPPPD could be a promising lead for the development of protopanaxadiol for non-small-cell lung cancer (NSCLC) drugs. [ABSTRACT FROM AUTHOR]

Background: Different approach ultrasound-guided superior laryngeal nerve block was used to aid awake intubation, but little is known which approach was superior. We aimed to compare the parasagittal and transverse approaches for ultrasound-guided superior laryngeal nerve block in adult patients undergoing awake intubation. Methods: Fifty patients with awake orotracheal intubation were randomized to receive either a parasagittal or transverse ultrasound-guided superior laryngeal nerve block. The primary outcome was patient's quality of airway anesthesia grade during insertion of the tube into the trachea. The patients' tube tolerance score after intubation, total procedure time, mean arterial pressure, heart rate, Ramsay sedation score at each time point, incidence of sore throat both 1 h and 24 h after extubation, and hoarseness before intubation, 1 h and 24 h after extubation were documented. Results: Patients' quality of airway anesthesia was significantly better in the parasagittal group than in the transverse group (median grade[IQR], 0 [0–1] vs. 1 [0–1], P = 0.036). Patients in the parasagittal approach group had better tube tolerance scores (median score [IQR],1[1–1] vs. 1 [1–1.5], P = 0.042) and shorter total procedure time (median time [IQR], 113 s [98.5–125.5] vs. 188 s [149.5–260], P < 0.001) than those in the transverse approach group. The incidence of sore throat 24 h after extubation was lower in the parasagittal group (8% vs. 36%, P = 0.041). Hoarseness occurred in more than half of the patients in parasagittal group before intubation (72% vs. 40%, P = 0.023). Conclusions: Compared to the transverse approach, the ultrasound-guided parasagittal approach showed improved efficacy in terms of the quality of airway topical anesthesia and shorter total procedure time for superior laryngeal nerve block. Trial registration: This prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20220425-014) and registered in the Chinese Clinical Trial Registry (19/6/2022, ChiCTR2200061287) prior to patient enrollment. Written informed consent was obtained from all participants in this trial. [ABSTRACT FROM AUTHOR]

Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/ml. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus. [ABSTRACT FROM AUTHOR]

Introduction: Sweet sorghum juice is a typical production feedstock for natural, eco-friendly sweeteners and beverages. Clostridium tyrobutyricum is one of the widely used microorganisms in the food industry, and its principal product, bio-butyric acid is an important food additive. There are no published reports of Clostridium tyrobutyricum producing butyric acid using SSJ as the sole substrate without adding exogenous substances, which could reach a food-additive grade. This study focuses on tailoring a cost-effective, safe, and sustainable process and strategy for their production and application. Methods: This study modeled the enzymolysis of non-reducing sugars via the first/second-order kinetics and added food-grade diatomite to the hydrolysate. Qualitative and quantitative analysis were performed using high-performance liquid chromatography, gas chromatography-mass spectrometer, full-scale laser diffraction method, ultra-performance liquid chromatography-tandem mass spectrometry, the cell double-staining assay, transmission electron microscopy, and Oxford nanopore technology sequencing. Quantitative realtime polymerase chain reaction, pathway and process enrichment analysis, and homology modeling were conducted for mutant genes. Results: The treated sweet sorghum juice showed promising results, containing 70.60 g/L glucose and 63.09 g/L fructose, with a sucrose hydrolysis rate of 98.29% and a minimal sucrose loss rate of 0.87%. Furthermore, 99.62% of the colloidal particles and 82.13% of the starch particles were removed, and the concentrations of hazardous substances were effectively reduced. A food microorganism Clostridium tyrobutyricum TGL-A236 with deep utilization value was developed, which showed superior performance by converting 30.65% glucose and 37.22% fructose to 24.1364 g/L bio-butyric acid in a treated sweet sorghum juice (1:1 dilution) fermentation broth. This titer was 2.12 times higher than that of the original strain, with a butyric acid selectivity of 86.36%. Finally, the Genome atlas view, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and evolutionary genealogy of genes: Non-supervised Orthologous (eggNOG) functional annotations, three-dimensional structure and protein cavity prediction of five non-synonymous variant genes were obtained. Conclusion: This study not only includes a systematic process flow and indepth elucidation of relevant mechanisms but also provides a new strategy for green processing of food raw materials, improving food microbial performance, and ensuring the safe production of food additives. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

BACKGROUND: While limited studies have evaluated the health impacts of thunderstorms and power outages (POs) separately, few have assessed their joint effects. We aimed to investigate the individual and joint effects of both thunderstorms and POs on respiratory diseases, to identify disparities by demographics, and to examine the modifications and mediations by meteorological factors and air pollution. METHODS: Distributed lag nonlinear models were used to examine exposures during three periods (i.e., days with both thunderstorms and POs, thunderstorms only, and POs only) in relation to emergency department visits for respiratory diseases (2005-2018) compared to controls (no thunderstorm/no PO) in New York State (NYS) while controlling for confounders. Interactions between thunderstorms and weather factors or air pollutants on health were assessed. The disparities by demographics and seasons and the mediative effects by particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) and relative humidity (RH) were also evaluated. RESULTS: Thunderstorms and POs were independently associated with total and six subtypes of respiratory diseases in NYS [highest risk ratio (RR) = 1.12; 95% confidence interval (CI): 1.08, 1.17], but the impact was stronger when they co-occurred (highest RR = 1.44; 95% CI: 1.22, 1.70), especially during grass weed, ragweed, and tree pollen seasons. The stronger thunderstorm/PO joint effects were observed on chronic obstructive pulmonary diseases, bronchitis, and asthma (lasted 0–10 d) and were higher among residents who lived in rural areas, were uninsured, were of Hispanic ethnicity, were 6–17 or over 65 years old, and during spring and summer. The number of comorbidities was significantly higher by 0.299–0.782/case. Extreme cold/heat, high RH, PM2.5, and ozone concentrations significantly modified the thunderstorm–health effect on both multiplicative and additive scales. Over 35% of the thunderstorm effects were mediated by PM2.5 and RH. CONCLUSION: Thunderstorms accompanied by POs showed the strongest respiratory effects. There were large disparities in thunderstorm-health associations by demographics. Meteorological factors and air pollution levels modified and mediated the thunderstorm-health effects. [ABSTRACT FROM AUTHOR]

Purpose: The family residence structure serves as a crucial pathway through which the family environment influences adolescents' development. Methods: Drawing on nationally representative data, this study employs multiple linear regression models and propensity score matching to examine the impact of various family residence structures on adolescents' non-cognitive abilities. Causal identification is achieved through propensity score matching, while robustness is assessed using methods such as augmented inverse probability weighting and placebo tests. Heterogeneity analysis is conducted based on gender and household registration, aiming to explore the mechanisms by which family residence structure affects adolescents' non-cognitive abilities. Results: The findings indicate that compared to two-parent co-residence households, three-generation co-residence families have significantly positive effects on emotional stability, conscientiousness, and agreeableness among adolescents. In contrast, skip-generation coresidence families exhibit significant negative effects on emotional stability and agreeableness in adolescents. Further investigation into the underlying mechanisms reveals that parental involvement and family socioeconomic status within three-generation co-residence families positively influence adolescents' non-cognitive abilities. Conclusion: This study highlights the importance of considering grandparents' role in adolescent growth and advocates for policy recommendations focusing on enhancing non-cognitive abilities in adolescents from skip-generation coresidence families. [ABSTRACT FROM AUTHOR]

At present, the demand for the simulation technology of infrared view is markedly expanding. However, the related main research orientations are influenced by numerous factors. Thus, the availability of infrared images for special scenes is difficult to determine, and their practical applications are limited. This study proposed a method based on generative adversarial network (GAN) to reveal its influence on the generation of infrared texture and produce infrared texture in infrared view simulation. By combining the needs of texture generation in infrared simulation and the superiority of image style transfer in texture generation, three algorithms for style transfer based on GAN, namely, Algorithms I, II, and III, were introduced to establish pretrained models. Simulation results of the three models were then evaluated using histograms, structural similarity (SSIM), and peak signal-to-noise ratio (PSNR), and the effects of colors of the infrared images in the texture generation were compared. The validity of these models was also verified. Results demonstrate that infrared images in a specified scene can be simulated without the need for a large number of training datasets, and the simulation images generated by transferring in black-and-white infrared style images are better than those in color infrared style images. The histogram evaluation index shows that Algorithm III is higher than Algorithms I and II by approximately 0.06. The SSIM evaluation index reveals that Algorithm II is higher than Algorithms I and II by 0.09 and 0.06 dB, respectively. The PSNR evaluation index indicates that Algorithm III is higher than Algorithms I and II by approximately 0.31 dB. Thus, this study provides a practical value in the field of infrared simulation technology. [ABSTRACT FROM AUTHOR]

The article introduces MetaMMF, a dynamic multimodal fusion framework for micro-video recommendation. It is reported that MetaMMF dynamically assigns parameters to fusion functions based on meta-learning, treating multimodal fusion for each micro-video as an independent task.It is further noted that extensive experiments show significant improvements over state-of-the-art models.

Excavation and unloading operations in underground rock engineering can cause strong disturbances to the original in situ stress, potentially leading to disasters such as spalling and rockburst. To address the inadequacy of strength analysis research, this study employs the energy analysis method. By analysing the relationship between different confining pressure unloading paths, a series of constant deviatoric stress direct and cyclic unloading triaxial tests were conducted to obtain the energy evolution process. Based on this, the energy evolution mechanism of the unloading confining pressure test path was revealed, and the influence of this path on the brittleness of the specimen was discussed. The research results indicate that confining pressure unloading leads to active energy release, triggering energy imbalance release and energy transfer mechanisms, which generate tensile and shear fractures, respectively, leading to energy dissipation. Throughout the entire test process, energy dissipation mainly comes from the elastic energy stored in the specimen before the unloading point, while the external work is relatively small. The elastic energy ratio continuously decreases from the unloading point. In addition, different triaxial confining pressure unloading tests can be regarded as the coupling of two stress path mechanisms: when the stress deviation remains unchanged, the spherical stress decreases, and when the stress deviation changes, the spherical stress remains unchanged. Furthermore, tensile microcracks weaken the brittleness before the peak and enhance it after the peak. The research results can guide the construction schemes of rock underground engineering. Highlights: The unloading of confining pressure leads to the active release of energy, triggering energy imbalance release and energy transfer mechanisms, which generate tensile and shear fractures, respectively. During the unloading of confining pressure, the dissipation of energy primarily originates from the elastic energy stored in the specimen before the unloading point, with less contribution from external work. Different triaxial unloading tests can be considered as the coupling of three energy mechanisms, namely energy saturation, energy imbalance release, and energy transfer mechanism. The tensile microcracks generated during the unloading process of the specimen have weakened the brittleness before the peak and enhanced it after the peak. [ABSTRACT FROM AUTHOR]

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in proinflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. [ABSTRACT FROM AUTHOR]

Background: Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. Methods: Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. Results: Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor β (IR-β) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-β phosphorylation, ultimately resulting in IR-β inactivation. This inactivation of IR-β suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. Conclusions: These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

Excessive Cd accumulation in soil reduces the production of numerous plants, such as Sophora tonkinensis Gagnep., which is an important and widely cultivated medicinal plant whose roots and rhizomes are used in traditional Chinese medicine. Applying a mixture of biochar and organic fertilizers improved the overall health of the Cd-contaminated soil and increased the yield and quality of Sophora. However, the underlying mechanism between this mixed fertilization and the improvement of the yield and quality of Sophora remains uncovered. This study investigated the effect of biochar and organic fertilizer application (BO, biochar to organic fertilizer ratio of 1:2) on the growth of Sophora cultivated in Cd-contaminated soil. BO significantly reduced the total Cd content (TCd) in the Sophora rhizosphere soil and increased the soil water content, overall soil nutrient levels, and enzyme activities in the soil. Additionally, the α diversity of the soil bacterial community had been significantly improved after BO treatment. Soil pH, total Cd content, total carbon content, and dissolved organic carbon were the main reasons for the fluctuation of the bacterial dominant species. Further investigation demonstrated that the abundance of variable microorganisms, including Acidobacteria, Proteobacteria, Bacteroidetes, Firmicutes, Chloroflexi, Gemmatimonadetes, Patescibacteria, Armatimonadetes, Subgroups_ 6, Bacillus and Bacillus_ Acidiceler, was also significantly changed in Cd-contaminated soil. All these alterations could contribute to the reduction of the Cd content and, thus, the increase of the biomass and the content of the main secondary metabolites (matrine and oxymatrine) in Sophora. Our research demonstrated that the co-application of biochar and organic fertilizer has the potential to enhance soil health and increase the productivity and quality of plants by regulating the microorganisms in Cd-contaminated soil. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical efficacy of glucosamine hydrochloride combined with compound osteopeptide injection for knee osteoarthritis (KOA). Methods: We retrospectively collected clinical data of 82 patients with KOA admitted to Shandong Weifang People's Hospital from April 2019 to September 2022. According to the treatment records, 35 patients received an intramuscular injection of compound osteopeptide (control group), and 47 patients received an injection of glucosamine hydrochloride combined with compound osteopeptide (observation group). We compared clinical efficacy, WOMAC scores, inflammatory factor and CD4+ and CD8+ levels, and the incidence of adverse reactions between the two groups. Results: The observation group's total efficacy (95.74%) was significantly higher than the control group's (80.00%; P<0.05). Treatment led to a significant reduction in WOMAC scores in both groups. In addition, the levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in the observation group were significantly lower than those in the control group (P<0.05); while the levels of CD4+ and CD8+ were significantly higher in the observation group (P<0.05). Conclusions: Compared with compound osteopeptide injection alone, glucosamine hydrochloride combined with compound osteopeptide injection is more effective for patients with KOA, with improved level of inflammatory factors and immune function. [ABSTRACT FROM AUTHOR]

Background: A precision healthcare approach is needed in the context of the healthcare system, especially as an effort to improve the self-management activities of diabetes patients. Accordingly, this study explores the perception of the possibility of implementing a precision healthcare program in hospitals through interviews with policymakers and health professionals. Methods: The purposive sampling via one-on-one, in-depth semi-structural interviews was conducted to collect the data in this study. The data saturation was achieved after interviewing 17 policymakers and health professionals in the selected hospitals. The participants discussed the possibility of a program being implemented in Indonesia and the challenges to implementing the program, as well as discovering the solutions. The narratives were analyzed by the Colaizzi phenomenological analytic method. Results: The three themes that were identified to illustrate the perception of the possibility of implementing precision health care programs at hospitals in Indonesia were as follows: 1) Precision health care for diabetes related to genetics, big data, and patient preference; 2) Barriers to implementing precision health care in Indonesian hospitals; and 3) The implementation of precision health care succeeded step by step. Conclusion: More time is needed to implement Indonesia’s precision healthcare concept. It requires time; however, applying the concept has great potential to be developed in reducing the risk of complications caused by diabetes mellitus in the future. [ABSTRACT FROM AUTHOR]

The development of highly active and selective electrocatalysts for the reduction of CO2 into valuable products presents a promising avenue for addressing the energy crisis and mitigating the greenhouse effect. In this study, we introduce a ligand-assisted supermolecule-derived red blood cell (RBC)-like catalyst composed of nickel and nitrogen-doped carbon (Ni@NC) for electrocatalytic carbon dioxide reduction reaction (eCO2RR) and Zn–CO2 battery applications. Among the various samples prepared, Ni@NC-950 exhibited the highest activity and demonstrated a faradaic efficiency of CO (FECO) greater than 90% across a wide potential range from −0.6 to −1.0 V [vs. reversible hydrogen electrode (RHE)], with a peak FECO of 97.8% achieved at −0.8 V. This translated to a remarkable partial current density (jCO) of 22.5 mA cm−2. When employed as the cathode catalyst in a Zn–CO2 battery, the Ni@NC-950 catalyst delivered a peak power density of 2.36 mW cm−2 at a current density of 10.97 mA cm−2. Importantly, the battery exhibited robust long-term discharge capability, operating continuously and steadily at 5 mA cm−2 for 20 hours. [ABSTRACT FROM AUTHOR]

Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation. [ABSTRACT FROM AUTHOR]

In an effort to enhance the efficiency and safety of open-pit mines, this study explores the optimization of end slope road parameters and slope structures, specifically focusing on unmanned driving lanes. A significant aspect of the study is the development of a truck trajectory offset model, which considers the different reaction times between automated sensors and human drivers in adapting to environmental changes. To test these concepts, the study uses numerical simulations to confirm the stability of the proposed end slope designs. Using Victory West Mine No. 1 as a case study, the research determines the optimized width for unmanned driving lanes and the maximum angle for the safe steepening of end slopes. The findings indicate that the optimized unmanned lane width for NTE240 mining dump trucks is 1743 mm, allowing for a 2-degree increase in the slope angle at the south end slope. This optimization leads to a steep mining stripping volume of 3.2735 million m3 and a coal output of 2.49628 million tons, maintaining a stripping ratio of 1.31 m3/t. These results demonstrate that unmanned driving road width optimization not only ensures slope safety but also significantly boosts the economic benefits of steep mining in open-pit mines. [ABSTRACT FROM AUTHOR]

Background: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. Methods: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. Results: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. Conclusions: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection. [ABSTRACT FROM AUTHOR]

To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agents have gained popularity. This study employs single-factor and multi-index orthogonal experimental design methods to investigate the seed coating formula and physical properties of Tartary buckwheat. The specific effects of each component on Tartary buckwheat seed germination are analyzed. The findings reveal that the seed coating agent formulated with 1.5% polyvinyl alcohol, 0.15% sodium alginate, 0.2% op-10, 0.1% polyacrylamide, 8% colorant, 3% ammonium sulfate, 1% potassium dihydrogen phosphate, and 0.15% carbendazim exhibits the most effective coating. It demonstrates optimal physical properties and promotes seed germination efficiently. The suspension rate of this seed coating agent reaches 91.12%, with a mere 2.13% coating shedding rate and 2.5% coating seed rot rate. Furthermore, it achieves a germination percentage of 99.17%, which is 20.84% higher than the lowest group. The germination potential and index are also significantly higher than the lowest group, with an increase of 20.84% and 26.56%, respectively. Additionally, the vitality index is 553.08, a 15.75% increase compared to the lowest group. The application of seed coating agents helps reduce seed resource loss, increase plant numbers, and ultimately enhance agricultural yields. This finding holds practical significance in agricultural production. [ABSTRACT FROM AUTHOR]

A comparative experimental and numerical study of the impact behaviour of carbon-fiber-reinforced thermoplastic (TP) and thermoset (TS) composites has been carried out. On the one hand, low velocity impact (LVI) tests were performed on TP and TS composites with different lay-up sequences at different energy levels, and the damage modes and microscopic damage mechanisms after impact were investigated using macroscale inspection, C-scan inspection, and X-ray-computed tomography. The comparative results show that the initial damage valve force under LVI depends not only on the material, but also on the layup sequence. The initial valve force of the P2 soft layer with lower stiffness is about 11% lower than that of the P1 quasi-isotropic layer under the same material, while the initial valve force of thermoplastic composites is about 28% lower than that of thermoset composites under the same stacking order. Under the same stacking order and impact energy level, the damage area and depth of TP composites are smaller than those of TS composites; while under the same material and impact energy level, the indentation depth of P2 plies is greater than that of P1 plies, and the damage area of P2 plies is smaller than that of P1 plies, but the change of thermoplastic composites is not as obvious as that of thermoset composites. This indicates that TP composites have a higher initial damage threshold energy and impact resistance at the same lay-up order, while increasing the lay-up ratio of the same material by 45° improves the impact resistance of the structure. In addition, a damage model based on continuum damage mechanics (CDM) was developed to predict different damage modes of thermoplastic composites during low velocity impact, and the analytical results were compared with the experimental results. At an impact energy of 4.45 J/mm, the error of the initial damage valve force is 5.26% and the error of the maximum impact force is 4.36%. The simulated impact energy and impact velocity curves agree with the experimental results, indicating that the finite element model has good reliability. [ABSTRACT FROM AUTHOR]

This paper discusses ways in which negative economic shocks captured by natural disasters can shape internal labor migration in China. The impact of negative economic shocks on migration depends on the combination of two opposite driving forces: (i) negative economic shocks can make staying in the affected area less profitable, thus enhancing returns to migration; (ii) the shocks can make it more difficult to migrate out, thus inducing a higher fixed cost of migration. Based on a nationwide dataset of China, this paper shows that when natural disasters were not severe, they caused migration out of rural areas. With sufficiently severe damage, however, the negative effect of natural disasters could be mitigated by villages' prior migrant networks. Specifically, with a severe shock, only clan members were able to migrate in response to natural disasters and enjoyed the complementary effects of prior migrant networks, as they could receive more help from social capital. [ABSTRACT FROM AUTHOR]

To promote the sustainable exploitation of open-pit coal resources, waste is used as backfill material to realize the comprehensive utilization of solid waste mine resources. We proposed a mining method that is a combination of the highwall mining and filling mining methods. Cemented paste backfill (CPB) samples were prepared with high-clay-mineral-content marl particles as aggregate and normal Portland cement, sulfoaluminate cement and gypsum as cementing materials. The physical and mechanical properties and microstructural evolution of CPB with different binder ratios under wetting–drying cycles were measured. The results showed that the CPB with 0–3 wetting–drying cycles underwent shear and tensile coalescence, and that with 4–10 cycles underwent shear coalescence. The unconfined compressive strength (UCS) and elastic modulus (EM) decreased exponentially with increasing number of wetting–drying cycles but decreased exponentially and cubically with increasing porosity, respectively. The EM is more sensitive to gypsum content than the UCS. CPB deterioration was divided into an initial deterioration stage and a secondary deterioration stage. The evolution curve of the total damage variable presents an 'S' shape, with an initial damage stage, an accelerated damage expansion stage, a decelerated damage expansion stage and an end damage stage. The research results provide a basis for improving the recovery rate of resources under highwall conditions, and the extensive utilization of stripping materials, and promote the coordinated development of coal resource exploitation and environmental protection. [ABSTRACT FROM AUTHOR]

Corydalis saxicola, an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola. Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola, accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C. saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl2, as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis. [ABSTRACT FROM AUTHOR]

Aim: East Asian subtropical evergreen broad-leaved forests (EBLFs) are composed of western and eastern subregions with different topographical and environmental conditions. The distribution shifts over time of plants in the two subregions are predicted to be different, but the difference has seldom been investigated. Methods: Potential distributions of 53 Magnoliaceae species (22 in the western and 31 in the eastern subregion) during the last glacial maximum (LGM), present, and the 2070s were predicted using MaxEnt based on 58 environmental variables. The changes in the distribution range size and centroid over time were analyzed. Species-level potential habitats were overlaid to uncover species diversity distribution, and the distributions over time were overlaid to discover long-term refugia. Results: At present, the potential distributions are significantly larger than those shown by the occurrence points. During the LGM, 20/22 species in the western subregion experienced increases in range size through downwards and southward migrations, while decreases in range size in the eastern subregion (27/31 species) were accompanied by northward and eastward migrations. In the future, range size declines and northward shifts will both be found; northwestward shifts will exist in most (20/22 species) species in the western subregion, while both northwest- and northeastward shifts will occur in the eastern subregion. The diversity hotspots experienced a slight southward shift in the past and upwards to the mountain region in the future in the western subregion; in the eastern subregion, shrinks occurred in eastern China in the past and shrinks were shown in all regions in the future. Long-term refugia-preserving diversity was found in the mountains across the entire EBLFs region. Main conclusions: Significant differences in distribution shifts from past to present and similar distribution shifts from present to future are revealed in the two subregions. Species diversity in both subregions experienced no significant shifts from past to future, and Magnoliaceae plants could be preserved in mountainous regions throughout the EBLFs. [ABSTRACT FROM AUTHOR]

Background: Prognosis of multiple myeloma (MM) patients with extramedullary disease (EMD) remains poor. T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow (BM) of MM patients. However, the immunosuppressive microenvironment and immune checkpoint receptors (ICRs) on CD8+ T cells in the EMD tissue of newly diagnosed MM (NDMM) patients have not been thoroughly studied. Methods: We investigated the expression levels of T cell immunoglobulin mucin-domain-containing-3 (TIM-3) and T-cell immunoglobulin and ITIM domain (TIGIT) on CD8+ T cells and the expression of their ligands (Galectin-9 and CD155) on myeloma cells in EMD tissue of NDMM patients. The expression levels of TIM-3 and TIGIT on T cells and their ligands (Galectin-9 and CD155) on myeloma cells were analyzed by multicolored fluorescent flow cytometry in the peripheral blood (PB), BM, and EMD tissue. Additionally, the expression of ICRs was compared among PB, BM, and EMD tissue. Results: The expression levels of TIGIT and TIM-3 on CD8+ T cell subsets, including CD8+ Naïve T (TN) cells and CD8+ terminally differentiated effector memory T (TEMRA) cells, were significantly higher in EMD than in PB (p < 0.05 for all). The expression levels of TIGIT and TIM-3 on CD8+ TN cells were higher in EMD than in BM (p < 0.05 for all). There were no differences in Galectin-9 and CD155 expression on myeloma cells among PB, BM, and EMD tissue. Conclusion: Our data add new evidence that T cells express increased TIGIT and TIM-3, suggesting that there may be T-cell exhaustion in EMD of patients with MM. [ABSTRACT FROM AUTHOR]

The effect of complex triaxial unloading confining pressure conditions on the mechanical behaviour and fracture mechanism of sandstone is investigated. Constant deviatoric stress direct and cyclic unloading confining pressure tests are carried out under two initial damage states. Based on the evolution law of deformation parameters, the influence of the initial damage and unloading rate on the mechanical properties of sandstone samples is expounded. The mechanism of tensile fracture development caused by the unloading of the confining pressure is proposed, and the engineering disasters that may be induced by this mechanism are discussed. The results show that the cyclic unloading confining pressure tests can replace direct unloading pressure tests to study the evolution process of the mechanical parameters of samples. The unloading confining pressure test under low damage conditions is more conducive to the study of unloading confining pressure failure. The unloading confining pressure produces obvious radial expansion and tensile cracks in the sample. With decreasing confining pressure, the bulk modulus of the samples under the two damage conditions gradually decreases. Under low damage conditions, the dilatancy angle decreases first and then increases, while under high damage conditions, it gradually increases. The unloading rate does not affect tensile crack development but does affect compression‒shear crack development, resulting in different strain responses of the two damaged specimens. The generation mechanism of macroscopic tensile cracks is as follows: the residual stress generated by the unloading of the confining pressure causes random tensile microcracks to nucleate, and the increase in microcrack density provides power for its development. The airfoil cracks gradually bend in the direction of the first principal stress, and the microcracks develop directionally and interconnect with each other to form macroscopic axial tensile cracks. The unloading of confining pressure produces tensile cracks perpendicular to the unloading direction, which may induce rock bursts and landslide disasters. The research results provide an important scientific basis for underground rock engineering construction and slope engineering prevention. Highlights: The unloading rate does not affect tensile crack development but does affect compression‒shear crack development. The residual stress generated by the unloading of the confining pressure causes random tensile microcracks to nucleate, and the increase in microcrack density provides power for its development. The unloading of confining pressure produces tensile cracks perpendicular to the unloading direction, which may induce rock bursts and landslide disasters. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Cell & Developmental Biology. It discusses recent advances in understanding skin disorders and the development of therapeutic strategies to treat them. The editorial highlights research on wound healing, including the use of peptides derived from amphibians, and the potential of cyclic peptides to promote wound healing and tissue injury prevention. It also explores the gene expression profile of melanocyte regeneration and melanoma, as well as the role of the α7-type nicotinic acetylcholine receptor in skin cancer. Additionally, the document discusses the association between gut microbiota and inflammatory dermatoses, such as psoriasis and atopic dermatitis. The editorial concludes by emphasizing the importance of further research in understanding the underlying mechanisms of skin disorders and developing effective treatments. [Extracted from the article]

The global pandemic of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an once-in-a-lifetime public health crisis. Among hundreds of millions of people who have contracted with or are being infected with COVID-19, the question of whether COVID-19 infection may cause long-term health concern, even being completely recovered from the disease clinically, especially immune system damage, needs to be addressed. Here, we performed seven-chain adaptome immune repertoire analyses on convalescent COVID-19 patients who have been discharged from hospitals for at least 6 months. Surprisingly, we discovered lymphopenia, reduced number of unique CDR3s, and reduced diversity of the TCR/BCR immune repertoire in convalescent COVID-19 patients. In addition, the BCR repertoire appears to be activated, which is consistent with the protective antibody titres, but serological experiments reveal significantly lower IL-4 and IL-7 levels in convalescent patients compared to those in healthy controls. Finally, in comparison with convalescent patients who did not receive post-hospitalization rehabilitation, the convalescent patients who received post-hospitalization rehabilitation had attenuated immune repertoire abnormality, almost back to the level of healthy control, despite no detectable clinic demographic difference. Overall, we report the potential long-term immunological impairment for COVID-19 infection, and correction of this impairment via post-hospitalization rehabilitation may offer a new prospect for COVID-19 recovery strategy. [ABSTRACT FROM AUTHOR]

Background: Nurses in Ophthalmology Department (OD) had a high risk of infection during the novel coronavirus disease 2019 (COVID-19) pandemic. This study examined the prevalence, correlates, and network structure of depression, and explored its association with quality of life (QOL) in Chinese OD nurses. Methods: Based on a cross-sectional survey, demographic and clinical data were collected. Depression was measured with the 9-item Self-reported Patient Health Questionnaire (PHQ-9), and QOL was measured using the World Health Organization Quality of Life Questionnaire-brief version (WHOQOL-BREF). Univariate analyses, multivariate logistic regression analyses, and network analyses were performed. Results: Altogether, 2,155 OD nurses were included. The overall prevalence of depression among OD nurses was 32.71% (95%CI: 30.73-34.70%). Multiple logistic regression analysis revealed that having family or friends or colleagues who were infected (OR = 1.760, p = 0.003) was significantly associated with higher risk of depression. After controlling for covariates, nurses with depression reported lower QOL (F (1, 2,155) = 596.784, p < 0.001) than those without depression. Network analyses revealed that 'Sad Mood', 'Energy Loss' and 'Worthlessness' were the key central symptoms. Conclusion: Depression was common among OD nurses during the COVID-19 pandemic. Considering the negative impact of depression on QOL and daily life, regular screening for depression, timely counselling service, and psychiatric treatment should be provided for OD nurses, especially those who had infected family/friends or colleagues. Central symptoms identified in network analysis should be targeted in the treatment of depression. [ABSTRACT FROM AUTHOR]

Mast cell leukemia is a rare and aggressive disease, predominantly with KIT D816V mutation. With poor response to conventional poly-chemotherapy, mast cell leukemia responded to the midostaurin treatment with a 50% overall response rate (ORR), but complete remission rate is approximately 0%. Therefore, the potential mechanisms of midostaurin resistance and the exact impacts of midostaurin on both gene expression profile and mast cell leukemia microenvironment in vivo are essential for design tailored combination therapy targeting both the tumor cells and the tumor microenvironment. Here we report a 59-year-old male mast cell leukemia patient with KIT F522C mutation treated with midostaurin. Single-cell sequencing of peripheral blood and whole exome sequencing (WES) of bone marrow were performed before and 10 months after midostaurin treatment. In accordance with the clinical response, compared to the pretreatment aberration, the decline of mast cells and increase of T-, NK, Bcells in peripheral blood, and the decrease of the KIT F522C mutation burden in bone marrow were observed. Meanwhile, the emergence of RUNX1 mutation, upregulations of genes expression (RPS27A, RPS6, UBA52, RACK1) on tumor cells, and increased frequencies of T and NK cells with TIGIT, CTLA4, and LAG3 expression were observed after midostaurin treatment, predicting the disease progression of this patient. As far as we know, this is the first case reporting the clinical, immunological, and molecular changes in mast cell leukemia patients before and after midostaurin treatment, illustrating the in vivo mechanisms of midostaurin resistance in mast cell leukemia, providing important clues to develop a sequential option to circumvent tumor progression after targeting oncogene addiction and prolong patients' survival. [ABSTRACT FROM AUTHOR]

The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy. [ABSTRACT FROM AUTHOR]