Non-thyroidal disease syndrome in patients with systemic lupus erythematosus: relation to disease inflammatory activity.

OBJECTIVE: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients. RESULTS: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS. CONCLUSIONS: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients.

Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis.

BACKGROUND: A triplet chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) is used to treat head and neck squamous cell carcinoma; however, it is toxic to bone marrow mesenchymal stem cells (BMSCs). We previously demonstrated that Ganoderma spore lipid (GSL) protect BMSCs against cyclophosphamide toxicity. In this study, we investigated the protective effects of GSL against TPF-induced BMSCs and hematopoietic damage. METHODS: BMSCs and C57BL/6 mice were divided into control, TPF, co-treatment (simultaneously treated with GSL and TPF for 2 days), and pre-treatment (treated with GSL for 7 days before 2 days of TPF treatment) groups. In vitro, morphology, phenotype, proliferation, senescence, apoptosis, reactive oxygen species (ROS), and differentiation of BMSCs were evaluated. In vivo, peripheral platelets (PLTs) and white blood cells (WBCs) from mouse venous blood were quantified. Bone marrow cells were isolated for hematopoietic colony-forming examination. RESULTS: In vitro, GSL significantly alleviated TPF-induced damage to BMSCs compared with the TPF group, recovering their morphology, phenotype, proliferation, and differentiation capacity (p < 0.05). Annexin V/PI and senescence-associated ß-galactosidase staining showed that GSL inhibited apoptosis and delayed senescence in TPF-treated BMSCs (p < 0.05). GSL downregulated the expression of caspase-3 and reduced ROS formation (p < 0.05). In vivo, GSL restored the number of peripheral PLTs and WBCs and protected the colony-forming capacity of bone marrow cells (p < 0.05). CONCLUSIONS: GSL efficiently protected BMSCs from damage caused by TPF and recovered hematopoiesis.

A comparison of machine learning methods for radiomics modeling in prediction of occult lymph node metastasis in clinical stage IA lung adenocarcinoma patients.

Background: Accurate prediction of occult lymph node metastasis (ONM) is an important basis for determining whether lymph node (LN) dissection is necessary in clinical stage IA lung adenocarcinoma patients. The aim of this study is to determine the best machine learning algorithm for radiomics modeling and to compare the performances of the radiomics model, the clinical-radilogical model and the combined model incorporate both radiomics features and clinical-radilogical features in preoperatively predicting ONM in clinical stage IA lung adenocarcinoma patients. Methods: Patients with clinical stage IA lung adenocarcinoma undergoing curative surgery from one institution were retrospectively recruited and assigned to training and test cohorts. Radiomics features were extracted from the preoperative computed tomography (CT) images of the primary tumor. Seven machine learning algorithms were used to construct radiomics models, and the model with the best performance, evaluated using the area under the curve (AUC), was selected. Univariate and multivariate logistic regression analyses were performed on the clinical-radiological features to identify statistically significant features and to develop a clinical model. The optimal radiomics and clinical models were integrated to build a combined model, and its predictive performance was assessed using receiver operating characteristic curves, Brier score, and decision curve analysis (DCA). Results: This study included 258 patients who underwent resection (training cohort, n=182; test cohort, n=76). Six radiomics features were identified. Among the seven machine learning algorithms, extreme gradient boosting (XGB) demonstrated the highest performance for radiomics modeling, with an AUC of 0.917. The combined model improved the AUC to 0.933 and achieved a Brier score of 0.092. DCA revealed that the combined model had optimal clinical efficacy. Conclusions: The superior performance of the combined model, based on XGB algorithm in predicting ONM in patients with clinical stage IA lung adenocarcinoma, might aid surgeons in deciding whether to conduct mediastinal LN dissection and contribute to improve patients' prognosis.

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients.

BACKGROUND: Dexmedetomidine and propofol are two sedatives used for long-term sedation. It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation. AIM: To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury. METHODS: Patients who underwent mechanical ventilation for > 72 h were randomly assigned to receive sedation with dexmedetomidine or propofol. The Richmond Agitation and Sedation Scale (RASS) was used to evaluate sedation effects, with a target range of -3 to 0. The primary outcomes were serum levels of S100-ß and neuron-specific enolase (NSE) every 24 h. The secondary outcomes were remifentanil dosage, the proportion of patients requiring rescue sedation, and the time and frequency of RASS scores within the target range. RESULTS: A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group, respectively. Baseline data were comparable between groups. No significant differences were identified between groups within the median duration of study drug infusion [52.0 (IQR: 36.0-73.5) h vs 53.0 (IQR: 37.0-72.0) h, P = 0.958], the median dose of remifentanil [4.5 (IQR: 4.0-5.0) µg/kg/h vs 4.6 (IQR: 4.0-5.0) µg/kg/h, P = 0.395], the median percentage of time in the target RASS range without rescue sedation [85.6% (IQR: 65.8%-96.6%) vs 86.7% (IQR: 72.3%-95.3), P = 0.592], and the median frequency within the target RASS range without rescue sedation [72.2% (60.8%-91.7%) vs 73.3% (60.0%-100.0%), P = 0.880]. The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance (69.2% vs 50.8%, P = 0.045). Serum S100-ß and NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation, respectively (all P < 0.05). CONCLUSION: Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Iron silicate perovskite and postperovskite in the deep lower mantle.

Ferromagnesian silicates are the dominant constituents of the Earth's mantle, which comprise more than 80% of our planet by volume. To interpret the low shear-velocity anomalies in the lower mantle, we need to construct a reliable transformation diagram of ferromagnesian silicates over a wide pressure-temperature (P-T) range. While MgSiO3 in the perovskite structure has been extensively studied due to its dominance on Earth, phase transformations of iron silicates under the lower mantle conditions remain unresolved. In this study, we have obtained an iron silicate phase in the perovskite (Pv) structure using synthetic fayalite (Fe2SiO4) as the starting material under P-T conditions of the lower mantle. Chemical analyses revealed an unexpectedly high Fe/Si ratio of 1.72(3) for the Pv phase in coexistence with metallic iron particles, indicating incorporation of about 25 mol% Fe2O3 in the Pv phase with an approximate chemical formula (Fe2+0.75Fe3+0.25)(Fe3+0.25Si0.75)O3. We further obtained an iron silicate phase in the postperovskite (PPv) structure above 95 GPa. The calculated curves of compressional (VP) and shear velocity (VS) of iron silicate Pv and PPv as a function of pressure are nearly parallel to those of MgSiO3, respectively. To the best of our knowledge, the iron silicate Pv and PPv are the densest phases among all the reported silicates stable at P-T conditions of the lower mantle. The high ferric iron content in the silicate phase and the spin-crossover of ferric iron at the Si-site above ~55 GPa should be taken into account in order to interpret the seismic observations. Our results would provide crucial information for constraining the geophysical and geochemical models of the lower mantle.

Are extra locking bolts or fibular plating more important in extreme nailing of distal tibia fractures? A cadaveric biomechanical analysis.

OBJECTIVES: In far-distal extra-articular tibia fracture "extreme" nailing, debate surrounds the relative biomechanical performance of plating the fibula compared with extra distal interlocks. This study aimed to evaluate several constructs for extreme nailing including one interlock (one medial-lateral interlock), one interlock + plate (one medial-lateral interlock with lateral fibula compression plating), and two interlocks (one medial-lateral interlock and one anterior-posterior interlock). METHODS: Fifteen pairs of fresh cadaver legs were instrumented with a tibial nail to the physeal scar. A 1 cm segment of bone was resected from the distal tibia 3.5 cm from the joint and an oblique osteotomy was made in the distal fibula. We loaded specimens with three different distal fixation constructs (one interlock, one interlock + plate, and two interlocks) through 10,000 cycles form 100N-700 N of axial loading. Load to failure (Newtons), angulation and displacement were also measured. RESULTS: Mean load to failure was 2092 N (one interlock), 1917 N (one interlock + plate), and 2545 N (two interlocks). Linear mixed effects modeling demonstrated that two interlocks had a load to failure 578 N higher than one interlock alone (95 % CI, 74N-1082 N; P = 0.02), but demonstrated no significant difference between one interlock and one interlock + plate. No statistically significant difference in rates or timing of displacement >2 mm or angulation >10° were demonstrated. CONCLUSIONS: When nailing far-distal extra-articular tibia and fibula fractures, adding a second interlock provides more stability than adding a fibular plate. Distal fibula plating may have minimal biomechanical effect in extreme nailing.

The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations.

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.

Draft Genome Sequence of Candida saopaulonensis from a Very Premature Infant with Sepsis.

The rare fungus Candida saopaulonensis has never been reported to be associated with human infection. We report the draft genome sequence of the first clinical isolate of C. saopaulonensis, which was isolated from a very premature infant with sepsis. This is the first genome assembly reaching the near-complete chromosomal level with structural annotation for this species, opening up avenues for exploring evolutionary patterns and genetic mechanisms of pathogenesis.

RNA velocity prediction via neural ordinary differential equation.

RNA velocity is a crucial tool for unraveling the trajectory of cellular responses. Several approaches, including ordinary differential equations and machine learning models, have been proposed to interpret velocity. However, the practicality of these methods is constrained by underlying assumptions. In this study, we introduce SymVelo, a dual-path framework that effectively integrates high- and low-dimensional information. Rigorous benchmarking and extensive studies demonstrate that SymVelo is capable of inferring differentiation trajectories in developing organs, analyzing gene responses to stimulation, and uncovering transcription dynamics. Moreover, the adaptable architecture of SymVelo enables customization to accommodate intricate data and diverse modalities in forthcoming research, thereby providing a promising avenue for advancing our understanding of cellular behavior.

Correlation Between Illness Uncertainty in Caregivers of Patients with Liver Cancer, Their Coping Styles, and Quality of Life.

Objective: This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer. Methods: Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers. Results: The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = -0.207, p = 0.003), physical status (r = -0.182, p = 0.008), psychological status (r = -0.200, p = 0.004), and social adaptation (r = -0.229, p = 0.001). Conclusion: The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.

Compilation of a self-management assessment scale for postoperative patients with aortic dissection.

Objective: The aim of this research was to compile a self-management assessment scale for patients with aortic dissection (AD). The questionnaire is useful in making the patient aware of the need for post-operative care in order to contribute to improving the outcome and quality of life. Methods: The initial version of the "postoperative self-management assessment scale for patients with aortic dissection" was developed using the Delphi expert consultation method based on qualitative research results, consultation of self-management-related literature, reference to the existing self-management scale, and self-efficacy theory, combined with the disease characteristics of AD. By using the convenience sampling method, a total of 201 patients with AD who had undergone surgery were selected as the research participants. The initial version of the scale was used for follow-up investigation, and the scale entries were evaluated and exploratory factor analysis carried out to form the formal version of the "postoperative self-management assessment scale for patients with aortic dissection." A total of 214 patients with AD after surgery were selected as the research participants. The formal version of the scale was used for follow-up investigation, and its reliability and validity were evaluated. Results: The formal version of the scale had 6 dimensions and 35 entries. The Cronbach's α coefficient for the total scale was 0.908, the split-half reliability was 0.790, and the test-retest reliability after 2 weeks was 0.471. The content validity index of the total scale was 0.963. Exploratory factor analysis yielded six common factors, and the cumulative contribution rate of variance was 66.303%. Confirmatory factor analysis showed that except for the incremental fit index, Tucker-Lewis index, and comparative fit index >0.85, slightly lower than 0.90, χ 2/df <3, root mean square of approximation <0.08, parsimonious goodness-of-fit index, and parsimonious normed fit index >0.50; all other model fitting requirements were satisfied, indicating that the model fitting was acceptable. Conclusion: We compiled the postoperative self-management assessment scale for patients with AD, which has demonstrated excellent reliability and validity and can be used as a tool to evaluate the postoperative self-management level in patients with aortic dissection.

Research on the effect of water-cooling steel pipe on preventing spontaneous combustion of coal pile and its thermal migration behavior.

During the storage and transportation process after mining, coal piles are placed in open environments, making them prone to self-heating and spontaneous combustion due to the nature of coal and factors like natural wind flow. In recent years, there have been frequent spontaneous combustion incidents involving coal piles, posing significant safety risks. To effectively prevent and control spontaneous combustion disasters in open-air coal storage piles, we propose a method involving the arrangement of water-cooling steel pipes within the coal piles. This method applies theories of coal spontaneous combustion mechanisms, porous media heat transfer, and non-isothermal pipeline heat transfer. The multi-physics coupling model of COMSOL numerical simulation software is used to analyze the spontaneous ignition process and prevention effect of open pit coal pile. In the model, the thin material transfer of porous media is taken as the oxygen concentration field, the heat transfer of porous media is taken as the temperature field, and the free and porous media flow is taken as the air seepage velocity field. The simulation results of the spontaneous combustion process in the coal pile indicate that the high-temperature zone of spontaneous combustion is situated within the range of 0.5 ~ 1.5 m inside the wind-facing surface and extends 0.5 m above the ground level. These findings serve as a basis for determining the optimal placement of water-cooling steel pipes within the coal pile. The simulation results of a single water-cooling steel pipe demonstrate a positive correlation between the cooling effect on the coal pile and the water cool flow, and a negative correlation with the water cool temperature. Additionally, the cooling radius of the water-cooling steel pipe is determined by the circumference of the pipe and remains unaffected by the water cool flow. Finally, simulations were conducted to evaluate the cooling effect of multiple rows of steel pipes, and optimal arrangement parameters were determined: a center distance between steel pipes of 1 m and a water cool flow rate of 1500 L/min. As a result, the onset of the self-heating period in the coal pile was delayed by 11 days, and the spontaneous combustion period was extended by 56 days. The arrangement of water-cooling steel pipes in the coal pile has demonstrated significant efficacy in preventing and controlling spontaneous combustion.

Brain endothelial GSDMD activation mediates inflammatory BBB breakdown.

The blood-brain barrier (BBB) protects the central nervous system from infections or harmful substances1; its impairment can lead to or exacerbate various diseases of the central nervous system2-4. However, the mechanisms of BBB disruption during infection and inflammatory conditions5,6 remain poorly defined. Here we find that activation of the pore-forming protein GSDMD by the cytosolic lipopolysaccharide (LPS) sensor caspase-11 (refs. 7-9), but not by TLR4-induced cytokines, mediates BBB breakdown in response to circulating LPS or during LPS-induced sepsis. Mice deficient in the LBP-CD14 LPS transfer and internalization pathway10-12 resist BBB disruption. Single-cell RNA-sequencing analysis reveals that brain endothelial cells (bECs), which express high levels of GSDMD, have a prominent response to circulating LPS. LPS acting on bECs primes Casp11 and Cd14 expression and induces GSDMD-mediated plasma membrane permeabilization and pyroptosis in vitro and in mice. Electron microscopy shows that this features ultrastructural changes in the disrupted BBB, including pyroptotic endothelia, abnormal appearance of tight junctions and vasculature detachment from the basement membrane. Comprehensive mouse genetic analyses, combined with a bEC-targeting adeno-associated virus system, establish that GSDMD activation in bECs underlies BBB disruption by LPS. Delivery of active GSDMD into bECs bypasses LPS stimulation and opens the BBB. In CASP4-humanized mice, Gram-negative Klebsiella pneumoniae infection disrupts the BBB; this is blocked by expression of a GSDMD-neutralizing nanobody in bECs. Our findings outline a mechanism for inflammatory BBB breakdown, and suggest potential therapies for diseases of the central nervous system associated with BBB impairment.

Genome-wide identification of the CNGC gene family and negative regulation of drought tolerance by HvCNGC3 and HvCNGC16 in transgenic Arabidopsis thaliana.

Cyclic nucleotide-gated ion channels (CNGCs), as non-selective cation channels, play essential roles in plant growth and stress responses. However, they have not been identified in Qingke (Hordeum vulgare L.). Here, we performed a comprehensive genome-wide identification and function analysis of the HvCNGC gene family to determine its role in drought tolerance. Phylogenetic analysis showed that 27 HvCNGC genes were divided into four groups and unevenly located on seven chromosomes. Transcription analysis revealed that two closely related members of HvCNGC3 and HvCNGC16 were highly induced and the expression of both genes were distinctly different in two extremely drought-tolerant materials. Transient expression revealed that the HvCNGC3 and HvCNGC16 proteins both localized to the plasma membrane and karyotheca. Overexpression of HvCNGC3 and HvCNGC16 in Arabidopsis thaliana led to impaired seed germination and seedling drought tolerance, which was accompanied by higher hydrogen peroxide (H2O2), malondialdehyde (MDA), proline accumulation and increased cell damage. In addition, HvCNGC3 and HvCNGC16-overexpression lines reduced ABA sensitivity, as well as lower expression levels of some ABA biosynthesis and stress-related gene in transgenic lines. Furthermore, Yeast two hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays revealed that HvCNGC3 and HvCNGC16 interacted with calmodulin/calmodulin-like proteins (CaM/CML), which, as calcium sensors, participate in the perception and decoding of intracellular calcium signaling. Thus, this study provides information on the CNGC gene family and provides insight into the function and potential regulatory mechanism of HvCNGC3 and HvCNGC16 in drought tolerance in Qingke.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential. METHOD: We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD. RESULTS: We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways. CONCLUSIONS: Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.

Facile design of FeCu metal-organic frameworks anchored on layer Ti3C2Tx MXene for high-performance electrochemical sensing of resorcinol.

This work reports the rational design of a composite material by growing FeCu-MOF-919 on the surface of layered Ti3C2Tx MXene. The introduction of Ti3C2Tx MXene simultaneously weakens the aggregation of FeCu-MOF-919 and Ti3C2Tx MXene, which increases the electrochemical reaction active site of the composite material and improves the electrochemical activity. Interestingly, the FeCu-MOF-919/Ti3C2Tx based sensors were used to detect resorcinol (RS) with a wide linear range (0.5-152.5 µM), excellent sensitivity (0.23 µA µM-1 cm-2), low limit of detection (LOD = 0.08 µM) and outstanding stability. Meanwhile, the sensor shows high repeatability of 1.07 % RSD, reproducibility of 1.47 % RSD and anti-interference performance. What's more, the sensor can be successfully used to detect RS in tap water with good recoveries (96.25-103.37 %, RSD ≤2.18 %), demonstrating that the FeCu-MOF-919/Ti3C2Tx exhibits significant potential as an advanced sensing apparatus for the surveillance of RS in the natural environment.

Associations of evening-type and insomnia symptoms with depressive symptoms among youths.

BACKGROUND: Evening-type and insomnia symptoms are significantly related to each other and independently associated with depressive symptoms, yet few studies have examined the potential interaction between these two conditions. Therefore, we aimed to examine the associations of evening-type and insomnia symptoms with depressive symptoms among Chinese youths, with a specific focus on the joint effects of the two conditions on depressive symptoms. METHODS: Participants aged between 12 and 25 were invited to participate in an online survey from December 15, 2022, to May 26, 2023. Multivariate logistic regression models and additive interaction models were used to examine the independent and joint effects of chronotypes and insomnia symptoms on depressive symptoms, respectively. RESULTS: Of the 6145 eligible youths, the prevalence of evening-type and insomnia symptoms were 24.9 % and 29.6 %, respectively. Both evening-type (adjusted OR, [AdjOR]: 3.21, 95 % CI: 2.80-3.67) and insomnia symptoms (AdjOR: 10.53, 95 % CI: 9.14-12.12) were associated with an increased risk of depressive symptoms. In addition, the additive interaction models showed that there is an enhanced risk of depression related to interaction between evening-type and insomnia symptoms (relative excess risk due to interaction, [RERI]: 11.66, 95 % CI: 7.21-16.11). CONCLUSIONS: The present study provided additional evidence demonstrating the presence of interaction between evening-type and insomnia symptoms, which can lead to a higher risk of depressive symptoms. Our findings argue the need for addressing both sleep and circadian factors in the management of depressive symptoms in young people.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

OMA1 competitively binds to HSPA9 to promote mitophagy and activate the cGAS-STING pathway to mediate GBM immune escape.

BACKGROUND: Immunotherapy with checkpoint inhibitors, especially those targeting programmed death receptor 1 (PD-1)/PD-1 ligand (PD-L1), is increasingly recognized as a highly promising therapeutic modality for malignancies. Nevertheless, the efficiency of immune checkpoint blockade therapy in treating glioblastoma (GBM) is constrained. Hence, it is imperative to expand our comprehension of the molecular mechanisms behind GBM immune escape (IE). METHODS: Protein chip analysis was performed to screen aberrantly expressed OMA1 protein in PD-1 inhibitor sensitive or resistant GBM. Herein, public databases and bioinformatics analysis were employed to investigate the OMA1 and PD-L1 relation. Then, this predicted relation was verified in primary GBM cell lines through distinct experimental methods. To investigate the molecular mechanism behind OMA1 in immunosuppression, a series of experimental methods were employed, including Western blotting, co-immunoprecipitation (Co-IP), mass spectrometry (MS), immunofluorescence, immunohistochemistry, and qRT-PCR. RESULTS: Our findings revealed that OMA1 competitively binds to HSPA9 to induce mitophagy and mediates the IE of GBM. Data from TCGA indicated a significant correlation between OMA1 and immunosuppression. OMA1 promoted PD-L1 levels in primary cells from patients with GBM. Next, the results of Co-IP and MS conducted on GBM primary cells revealed that OMA1 interacts with HSPA9 and induces mitophagy. OMA1 promoted not only cGAS-STING activity by increasing mitochondrial DNA release but also PD-L1 transcription by activating cGAS-STING. Eventually, OMA1 has been found to induce immune evasion in GBM through its regulation of PD-1 binding and PD-L1 mediated T cell cytotoxicity. CONCLUSIONS: The OMA1/HSPA9/cGAS/PD-L1 axis is elucidated in our study as a newly identified immune therapeutic target in GBM.

Origin of functional de novo genes in humans from "hopeful monsters".

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new. In this short review, we will summarize the definition and features of human de novo genes and clarify their process of origination from ancestral non-coding genomic regions. In addition, we define the favored precursors, or "hopeful monsters," for the origin of de novo genes and present a discussion of the functional significance of these young genes in brain development and tumorigenesis in humans. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.