Metabolic subtypes and immune landscapes in esophageal squamous cell carcinoma: prognostic implications and potential for personalized therapies.

BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.

Assessing inter-intraspecific variability of leaf vulnerability to embolism for 10 alpine Rhododendron species growing in Southwestern China.

Alpine Rhododendron species are prominent constituents and renowned ornamental plants in alpine ecosystems. Consequently, evaluating the genetic variation in embolism resistance within the genus Rhododendron and predicting their adaptability to future climate change is important. Nevertheless, the assessment of embolism resistance in Rhododendron species remains limited. This investigation aimed to examine leaf vulnerability to embolism across ten alpine Rhododendron species, which are frequently employed as ornamental species in Rhododendron forests in Southwest China. The study analyzed the correlation between embolism resistance and various morphological traits, while also conducting water control experiments to evaluate the relationship between embolism resistance and drought resistance. The outcomes indicated pronounced variations in leaf vulnerability to embolism among species, as reflected by the water potential at 50% of embolized pixels (P50 ). Furthermore, the leaf P50 exhibited a significant positive correlation with vessel diameter (D) (R2 = 0.44, P = 0.03) and vessel wall span (b) (R2 = 0.64, P = 0.005), while displaying a significant negative correlation with vessel reinforcement ((t/b)2 ) (R2 = 0.67, P = 0.004). These findings underscore the reliability of selecting species based on embolism vulnerability to preserve the diversity of alpine ecosystems and foster resilience to climate change.

Dipole-multipole plasmonic coupling between gold nanorods and titanium nitride nanoparticles for enhanced photothermal conversion.

The plasmonic photothermal conversion efficiency can be enhanced by coupling among plasmonic atoms or plasmonic molecules due to the amplified local electric field and extinction cross-section. Recently, it has been theoretically proved that hybridization between dipolar modes and higher order modes can provide higher enhancement than that among dipolar modes in terms of both near- and far-field, which may lead to a higher photothermal conversion rate. In this work, we systematically investigated the photothermal conversion enhancement of plasmonic coupling between a dipolar mode of a titanium nitride nanoparticle (TiN NP) and a higher order mode of a gold nanorod (Au NR), which was compared to that of coupling among TiN NPs' dipolar modes. We evaluated the photothermal conversion efficiency of dipole-dipole coupling and dipole-multipole coupling in the nanocluster under the illumination of a monochromatic laser of 808 nm wavelength and simulated solar light, respectively. Both experimental tests and numerical simulations suggested that the plasmonic dipole-multipole coupling exhibited higher enhancement in photothermal conversion than dipole-dipole plasmonic coupling.

Response of dissolved inorganic carbon dynamics to simulated tidal hydrological processes in coastal wetlands.

To clarify the impacts of tidal hydrological process shifts caused by sea level rise on the blue carbon cycle, a typical coastal wetland in Jiaozhou Bay was selected for this study. The soils of Suaeda salsa (SS) and Phragmites australis (PA) wetlands were collected to simulate the effects of three types of tidal hydrological processes (Neap tide group, NT; Middle tide group, MT; Spring tide group, ST) on the soil-water dissolved inorganic carbon (DIC) dynamic. The results showed that the concentration of water dissolved inorganic carbon (WDIC) increased rapidly (115% higher) at early stage (days 0-4) under the influence of the tidal hydrological processes. Significant differences were found in WDIC concentration during different tidal hydrological processes (P < 0.05), which were expressed as MT (52.7 ± 13.3 mg L-1) > ST (52.5 ± 12.9 mg L-1) > NT (48.4 ± 10.1 mg L-1). After experiencing the tidal hydrological processes, the soil DIC content showed a net accumulation (55.1 ± 1.29 mg L-1vs. 46.7 ± 1.76 mg L-1, P < 0.001), whereas the soil inorganic carbon (SIC) decreased (2.73 ± 1.64 mg L-1vs. 4.61 ± 1.71 mg L-1), which may be attributed to the dissolution of SIC caused by the uptake of CO2 to form DIC. The accumulation of soil DIC was directly related to the SIC (λ = 1.03, P < 0.01), and indirectly related to soil nutrients (SOC substrate, λ = -0.003) and microbes (microbial biomass, λ = -0.10), and was mainly dominated by abiotic processes (abiotic: 58.1 ± 1.8% to 82.7 ± 2.46% vs. biotic: 17.4 ± 2.46% to 41.9 ± 1.76%). The increase of tidal frequency generally inhibited the accumulation of soil DIC content and promoted the output of WDIC. However, the response of soil DIC in different wetland types to tidal frequency was divergent, which was mainly regulated by the trade-off between soil nutrients and SIC content. Taken together, tidal hydrological processes and their frequency changes reshaped DIC dynamics, promoted the dissolution of SIC and the potential uptake of CO2. These findings enhance the comprehension of the inorganic carbon cycle within coastal wetlands, particularly amidst the backdrop of climate change and the rising sea levels.

Bridging the relationship between physical exercise and mental health in adolescents based on network analysis.

Although physical exercise has been recommended as a useful means of enhancing the mental health of adolescents, the exact mechanisms through which physical exercise plays a role are unclear. Both physical exercise and mental health are complex concepts with multiple facets, and traditional methods may constrain the manifestations of their mapping relationships. This research aimed to find the bridging connections between physical exercise and mental health. Mental health and physical exercise behaviors were assessed using the Symptom Checklist 90 (SCL-90) and the Adolescent Physical Activity Questionnaire (PAQ-A) in 9072 Chinese adolescents, respectively. Network analysis was utilized to construct the mental health-physical exercise network and to analyze the relationships between individual physical exercise behaviors and mental health symptoms. Core and bridging nodes were identified based on expected influence (EI) and bridge expected influence (BEI). Gender differences were also examined. The results revealed specific and distinct pathways between physical exercise and mental health (e.g., winter sports-obsessive-compulsive symptoms, winter sports-phobia). For both males and females, anxiety, depression, interpersonal sensitivity, ball sports, and evening activity were the most central symptoms/behaviors, reflecting their relative significance in their respective associations. The nodes with the highest BEI were obsessive-compulsive symptoms and physical education, showing negative associations with nodes in the other community. Furthermore, in the male group, somatization and winter sports stood out as the most positive bridge nodes. Conversely, in the female group, interpersonal sensitivity and sports games were the most positive bridge nodes. These findings illuminate the pathways linking physical exercise and mental health, supporting the implementation of physical exercise in a more elaborate way.

Role of modifiable organisational factors in decreasing barriers to mental healthcare: a longitudinal study of mission meaningfulness, team relatedness and leadership trust among Canadian military personnel deployed on Operation LASER.

OBJECTIVES: The literature presents complex inter-relationships among individual-factors and organisational-factors and barriers to seeking mental health support after deployment. This study aims to quantify longitudinal associations between such factors and barriers to mental health support. DESIGN: A longitudinal online survey of Canadian Armed Forces (CAF) personnel collected data at 3 months post-deployment (T1), 6 months post-deployment (T2) and 1 year post-deployment (T3). SETTING: In 2020, as part of Canada's response to the COVID-19 pandemic, 2595 CAF personnel deployed on Operation LASER to support civilian long-term care facilities in Québec and Ontario. PARTICIPANTS: All Operation LASER personnel were invited to participate: 1088, 582 and 497 responded at T1, T2 and T3, respectively. Most respondents were young, male, non-commissioned members. MAIN OUTCOME MEASURES: Barriers to mental health support were measured using 25 self-reported items and grouped into theory-based factors, including eight factors exploring care-seeking capabilities, opportunities and motivations; and two factors exploring moral issues. Logistic regressions estimated the crude and adjusted associations of individual and organisational characteristics (T1) with barriers (T2 and T3). RESULTS: When adjusting for sex, military rank and mental health status, increased meaningfulness of deployment was associated with lower probability of endorsing barriers related to conflicts with career goals and moral discomfort in accessing support at T2. Higher scores in trust in leadership were associated with lower probability of endorsing four barriers at T2, and five barriers at T3. CONCLUSIONS: We identified several modifiable organisational-level characteristics that may help reduce perceived barriers to mental health support in military and other high-risk occupational populations. Results suggest that promoting individuals' sense of purpose, instilling trust in leadership and promoting relatedness among team members may improve perceptions of access to mental health supports in the months following a domestic deployment or comparable occupational exposure.

Dexmedetomidine Alleviates Propofol Infusion Syndrome-Induced Myocardial Injury through Inhibiting Ferroptosis Associated with Accumulation of Reactive Oxygen Species.

OBJECTIVE: To observe the effect of dexmedetomidine (Dex) on propofol infusion syndrome (PRIS)-induced myocardial injury and explore the roles of ferroptosis and accumulation of reactive oxygen species (ROS). METHODS: Eighteen male Sprague-Dawley rats were evenly divided into the control group, model group and test group (n=6/group) based on a computer-generated random number table. The PRIS-induced myocardial injury model was prepared in the model group and test group through a 12 h-caudal vein infusion of 1% propofol medium and long chain fat emulsion injection at a rate of 20 mg·Kg-1·h-1 for the first 6 h and 40 mg·Kg-1·h--1 for the last 6 h, and meanwhile the test group was treated by Dex. The control group received the same amount of normal saline through the caudal vein. The following indicators were compared between the three groups including myocardial pathological results, enzymatic changes of myocardial injury, ferroptosis of myocardial cells and accumulation of ROS. RESULTS: Dex alleviated the myocardial pathological injury caused by propofol infusion. Propofol infusion caused time-dependent enzymatic changes of myocardial injury and Dex alleviated these enzymatic changes. Dex alleviated the ferroptosis of myocardial cells and accumulation of ROS caused by propofol infusion. CONCLUSIONS: Dex could alleviate PRIS-induced myocardial injury by inhibiting ferroptosis associated with accumulation of ROS. Combined sedation using propofol and Dex might be a potential strategy for the prevention and treatment of PRIS-induced cardiotoxicity.

Characteristics of symptoms and development of psychological status in late Chinese adolescence.

BACKGROUND: Many late adolescents experience a state of psychological sub-health, requiring early recognition and intervention. This study aims to assess the psychological state of late Chinese adolescents and uncover developmental trend of mental health through network analysis. METHOD: We analyzed data from 9072 Chinese high school adolescents in Shandong Province surveyed in 2020-2021, and divided them into the normal, the suspected, and the abnormal groups based on Symptom Checklist 90 (SCL-90) scores. Network analysis was employed to identify the core symptoms and bridge symptoms across different states. RESULTS: Anxiety and depression were the most central symptoms, without gender differences. Core symptoms, network structure, and network invulnerability varied across different psychological states. The abnormal group exhibited the highest value of natural connectivity, followed by the suspected and normal groups. This pattern extended to bridge networks. While not meeting diagnostic criteria, the suspected group demonstrated abnormalities in network edge invariance and global strength invariance. LIMITATIONS: The cross-sectional design cannot establish causality, and biases in self-report measurements cannot be ignored. CONCLUSION: Compared to traditional scale indicators, network structural characteristics may be a more sensitive assessment indicator.

Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells.

In this editorial, we offer our perspective on the groundbreaking study entitled "Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells", recently published in World Journal of Stem Cells. Despite over three decades of research on the clinical application of mesenchymal stem cells (MSCs), only a few therapeutic products have made it to clinical use, due to multiple preclinical and clinical challenges yet to be addressed. The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics, which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs. As we delve deeper into the intricacies of pretreatment methodologies, we anticipate a transformative shift in the landscape of MSC-based therapies, ultimately contributing to improved patient outcomes and advancing the field as a whole.

Meningitis in neonate caused by Mycoplasma hominis: A case report.

Background: Mycoplasma hominis (M. hominis) commonly colonizes the genitourinary tract of adult women and may result in neonatal meningitis through vertical transmission. Although there are few case reports, if the treatment is not conducted timely, the disease progresses rapidly, which may lead to serious complications and a poor prognosis. Case presentation: In the present study, a 10-day-old full-term neonate who presented with fever as the initial symptom and was eventually diagnosed with meningitis caused by M. hominis was reported. In the present case, the pathogen was not detected during the initial routine investigations, and the therapeutic effects of empiric antibiotic therapy were poor. Metagenomic next-generation sequencing (mNGS) in the cerebrospinal fluid (CSF) was conducted with the detection of M. hominis, and the antibiotics were adjusted to moxifloxacin combined with doxycycline. The clinical symptoms of the pediatric patient disappeared with an improvement in related laboratory results. Conclusion: It was difficult to detect M. hominis by routine bacterial culture. Therefore, M. hominis infection should be checked for in children with meningitis who had a negative result in CSF culture and poor therapeutic effects of empirical medication. mNGS in CSF should be conducted as soon as possible, and sensitive antibiotics should be administered in time to reduce the incidence of complications and improve the prognosis.

Interpenetrated Multinetwork Hybrid Aerogels by Layered Montmorillonite and One-Dimensional Hydroxyapatite Fibers for Heat and Fire Insulation.

It is of practical significance to develop aerogels with effective thermal insulation characteristics together with fireproof properties as well as high mechanical strength. Here, an interpenetrated multinetwork hybrid aerogel realizing thermal insulation, flame retardancy, and high compression modulus is demonstrated. Specifically, one-dimensional hydroxyapatite nanowires (HAP) played dual roles as the aerogel support skeleton to entangle with layered montmorillonite (MMT) each other to form a three-dimensional interpenetrated multinetwork structure and to optimize the thermal conductivity by adjusting the pore space in current HAP/MMT/PVA hybrid aerogels. Therefore, the interpenetrated multinetwork hybrid aerogels exhibit superior thermal insulation performance in room temperature (0.033 W m-1 K-1, 298 K, air conditions) and largely enhanced ultrahigh compression modulus (80 MPa). Moreover, the obtained hybrid aerogels also exhibit excellent flame retardancy and self-extinguishing smoke suppression properties (peak heat release rate and total smoke production as low as 92.44 kW m-2 and 0.1 m2, respectively), which is the outstanding interpenetrated multinetwork hybrid aerogel that has achieved synergistic improvement in heat and fire insulation and mechanical performance. Therefore, the interpenetrated multinetwork hybrid aerogels are promising candidates for efficient heat insulation, fire prevention, and mechanically robust applications.

PANoptosis signaling enables broad immune response in psoriasis: From pathogenesis to new therapeutic strategies.

Background: Accumulating evidence suggests that regulated cell death, such as pyroptosis, apoptosis, and necroptosis, is deeply involved in the pathogenesis of psoriasis. As a newly recognized form of systematic cell death, PANoptosis is involved in a variety of inflammatory disorders through amplifying inflammatory and immune cascades, but its role in psoriasis remains elusive. Objectives: To reveal the role of PANoptosis in psoriasis for a potential therapeutic strategy. Methods: Multitranscriptomic analysis and experimental validation were used to identify PANoptosis signaling in psoriasis. RNA-seq and scRNA-seq analyses were performed to establish a PANoptosis-mediated immune response in psoriasis, which revealed hub genes through WGCNA and predicted disulfiram as a potential drug. The effect and mechanism of disulfiram were verified in imiquimod (IMQ)-induced psoriasis. Results: Here, we found a highlighted PANoptosis signature in psoriasis patients through multitranscriptomic analysis and experimental validation. Based on this, two distinct PANoptosis patterns (non/high) were identified, which were the options for clinical classification. The high-PANoptosis-related group had a higher response rate to immune cell infiltration (such as M1 macrophages and keratinocytes). Subsequently, WGCNA showed the hub genes (e.g., S100A12, CYCS, NOD2, STAT1, HSPA4, AIM2, MAPK7), which were significantly associated with clinical phenotype, PANoptosis signature, and identified immune response in psoriasis. Finally, we explored disulfiram (DSF) as a candidate drug for psoriasis through network pharmacology, which ameliorated IMQ-mediated psoriatic symptoms through antipyroptosis-mediated inflammation and enhanced apoptotic progression. By analyzing the specific ligand-receptor interaction pairs within and between cell lineages, we speculated that DSF might exert its effects by targeting keratinocytes directly or targeting M1 macrophages to downregulate the proliferation of keratinocytes. Conclusions: PANoptosis with its mediated immune cell infiltration provides a roadmap for research on the pathogenesis and therapeutic strategies of psoriasis.

VDAC1, as a downstream molecule of MLKL, participates in OGD/R-induced necroptosis by inducing mitochondrial damage.

Ischemia-reperfusion (I/R) injury constitutes a significant risk factor for a range of diseases, including ischemic stroke, myocardial infarction, and trauma. Following the restoration of blood flow post-tissue ischemia, oxidative stress can lead to various forms of cell death, including necrosis, apoptosis, autophagy, and necroptosis. Recent evidence has highlighted the crucial role of mitochondrial dysfunction in I/R injury. Nevertheless, there remains much to be explored regarding the molecular signaling network governing cell death under conditions of oxidative stress. Voltage-dependent anion channel 1 (VDAC1), a major component in the outer mitochondrial membrane, is closely involved in the regulation of cell death. In a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R), which effectively simulates I/R injury in vitro, our study reveals that OGD/R induces VDAC1 oligomerization, consequently exacerbating cell death. Furthermore, we have revealed the translocation of mixed lineage kinase domain-like protein (MLKL) to the mitochondria, where it interacts with VDAC1 following OGD/R injury, leading to an increased mitochondrial membrane permeability. Notably, the inhibition of MLKL by necrosulfonamide hinders the binding of MLKL to VDAC1, primarily by affecting the membrane translocation of MLKL, and reduces OGD/R-induced VDAC1 oligomerization. Collectively, our findings provide preliminary evidence of the functional association between MLKL and VDAC1 in the regulation of necroptosis.

Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases.

Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.