Overexpression of Larch SCL6 Inhibits Transitions from Vegetative Meristem to Inflorescence and Flower Meristem in Arabidopsis thaliana (L.) Heynh.

SCARECROW-LIKE6 (SCL6) plays a role in the formation and maintenance of the meristem. In Larix kaempferi (Lamb.) Carr., an important afforestation tree species in China, SCL6 (LaSCL6) has two alternative splicing variants-LaSCL6-var1 and LaSCL6-var2-which are regulated by microRNA171. However, their roles are still unclear. In this study, LaSCL6-var1 and LaSCL6-var2 were transformed into the Arabidopsis thaliana (L.) Heynh. genome, and the phenotypic characteristics of transgenic A. thaliana, including the germination percentage, root length, bolting time, flower and silique formation times, inflorescence axis length, and branch and silique numbers, were analyzed to reveal their functions. It was found that LaSCL6-var1 and LaSCL6-var2 overexpression shortened the root length by 41% and 31%, respectively, and increased the inflorescence axis length. Compared with the wild type, the bolting time in transgenic plants was delayed by approximately 2-3 days, the first flower and silique formation times were delayed by approximately 3-4 days, and the last flower and silique formation times were delayed by about 5 days. Overall, the life cycle in transgenic plants was prolonged by approximately 5 days. These results show that LaSCL6 overexpression inhibited the transitions from the vegetative meristem to inflorescence meristem and from the flower meristem to meristem arrest in A. thaliana, revealing the roles of LaSCL6-var1 and LaSCL6-var2 in the fate transition and maintenance of the meristem.

Elimination of Intragrain Defect to Enhance the Performance of FAPbI3 Perovskite Solar Cells by Ionic Liquid.

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

Glucan polysaccharides isolated from Lactarius hatsudake Tanaka mushroom: Structural characterization and in vitro bioactivities.

Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with ß-(1,3)-Glcp as the main chain and ß-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments.

Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression.

Background/Aims: : Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: : This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: : Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions: : In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Characterization and Assessment of Native Lactic Acid Bacteria from Broiler Intestines for Potential Probiotic Properties.

Probiotics are the most promising alternative to antibiotics for improving animal production and controlling pathogenic infections, while strains derived from natural hosts are considered highly desirable due to their good adaptation to the gastrointestinal tract. The aim of this study was to screen Lactobacillus with broad-spectrum antibacterial activity from broilers fed an antibiotic-free diet and evaluate their potential as poultry probiotics. A total of 44 lactic acid bacteria (LAB) strains were isolated from the intestines of healthy broilers, among which 3 strains exhibited outstanding antimicrobial activity and were subsequently identified through 16S rRNA sequencing as Enterococcus faecium L8, Lactiplantibacillus plantarum L10, and Limosilactobacillus reuteri H11. These three isolates demonstrated potent bacteriostatic activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella cholerae, with inhibition zones ranging from 15.67 ± 1.53 to 21.33 ± 0.58 mm. The selected LAB strains exhibited high tolerance to acid and bile salts, with L. reuteri H11 displaying the highest survival rate (ranging from 34.68% to 110.28%) after exposure to 0.3% (w/v) bile salts for 6 h or a low pH environment (pH 2, 2.5, and 3) for 3 h. Notably, L. reuteri H11 outperformed other strains in terms of hydrophobicity (84.31%), auto-aggregation (53.12%), and co-aggregation with E. coli ATCC 25922 (36.81%) and S. aureus ATCC 6538 (40.20%). In addition, the three LAB isolates were either fully or moderately susceptible to the tested antibiotics, except for strain L8, which resisted gentamycin and vancomycin. Consequently, these three LAB strains, especially L. reuteri H11, isolated from the intestines of broiler chickens, represent promising probiotic candidates that can be employed as feed additives to enhance production performance and control poultry pathogens.

The Shape Effect of Acoustic Micropillar Array Chips in Flexible Label-Free Separation of Cancer Cells.

The precise isolation of circulating tumor cells (CTCs) from blood samples is a potent tool for cancer diagnosis and clinical prognosis. However, CTCs are present in extremely low quantities in the bloodstream, posing a significant challenge to their isolation. In this study, we propose a non-contact acoustic micropillar array (AMPA) chip based on acoustic streaming for the flexible, label-free capture of cancer cells. Three shapes of micropillar array chips (circular, rhombus, and square) were fabricated. The acoustic streaming characteristics generated by the vibration of microstructures of different shapes are studied in depth by combining simulation and experiment. The critical parameters (voltage and flow rate) of the device were systematically investigated using microparticle experiments to optimize capture performance. Subsequently, the capture efficiencies of the three micropillar structures were experimentally evaluated using mouse whole blood samples containing cancer cells. The experimental results revealed that the rhombus microstructure was selected as the optimal shape, demonstrating high capture efficiency (93%) and cell activity (96%). Moreover, the reversibility of the acoustic streaming was harnessed for the flexible release and capture of cancer cells, facilitating optical detection and analysis. This work holds promise for applications in monitoring cancer metastasis, bio-detection, and beyond.

Timescale correlation of shallow trap states increases electrochemiluminescence efficiency in carbon nitrides.

Highly efficient interconversion of different types of energy plays a crucial role in both science and technology. Among them, electrochemiluminescence, an emission of light excited by electrochemical reactions, has drawn attention as a powerful tool for bioassays. Nonetheless, the large differences in timescale among diverse charge-transfer pathways from picoseconds to seconds significantly limit the electrochemiluminescence efficiency and hamper their broad applications. Here, we report a timescale coordination strategy to improve the electrochemiluminescence efficiency of carbon nitrides by engineering shallow electron trap states via Au-N bond functionalization. Quantitative electrochemiluminescence kinetics measurements and theoretic calculations jointly disclose that Au-N bonds endow shallow electron trap states, which coordinate the timescale of the fast electron transfer in the bulk emitter and the slow redox reaction of co-reagent at diffusion layers. The shallow electron trap states ultimately accelerate the rate and kinetics of emissive electron-hole recombination, setting a new cathodic electrochemiluminescence efficiency record of carbon nitrides, and empowering a visual electrochemiluminescence sensor for nitrite ion, a typical environmental contaminant, with superior detection range and limit.

Single-Molecule Discrimination of Saccharides Using Carbon Nitride Nanopores.

Structural complexity brings a huge challenge to the analysis of sugar chains. As a single-molecule sensor, nanopores have the potential to provide fingerprint information on saccharides. Traditionally, direct single-molecule saccharide detection with nanopores is hampered by their small size and weak affinity. Here, a carbon nitride nanopore device is developed to discern two types of trisaccharide molecules (LeApN and SLeCpN) with minor structural differences. The resolution of LeApN and SLeCpN in the mixture reaches 0.98, which has never been achieved in solid-state nanopores so far. Monosaccharide (GlcNAcpN) and disaccharide (LacNAcpN) can also be discriminated using this system, indicating that the versatile carbon nitride nanopores possess a monosaccharide-level resolution. This study demonstrates that the carbon nitride nanopores have the potential for conducting structure analysis on single-molecule saccharides.

Orthogonal printing of uniform nanocomposite monolayer and oriented organic semiconductor crystals for high-performance nano-crystal floating gate memory.

Inkjet printing is of great interest in the preparation of optoelectronic and microelectronic devices due to its low cost, low process temperature, versatile material compatibility, and ability to precisely manufacture multi-layer devices on demand. However, interlayer solvent erosion is a typical problem that limits the printing of organic semiconductor devices with multi-layer structures. In this study, we proposed a solution to address this erosion problem by designing polystyrene-block-poly(4-vinyl pyridine)-grafted Au nanoparticles (Au@PS-b-P4VP NPs). With a colloidal ink containing the Au@PS-b-P4VP NPs, we obtained a uniform monolayer of Au nano-crystal floating gates (NCFGs) embedded in the PS-b-P4VP tunneling dielectric (TD) layer using direct-ink-writing (DIW). Significantly, PS-b-P4VP has high erosion resistance against the semiconductor ink solvent, which enables multi-layer printing. An active layer of semiconductor crystals with high crystallinity and well-orientation was obtained by DIW. Moreover, we developed a strategy to improve the quality of the TD/semiconductor interface by introducing a polystyrene intermediate layer. We show that the NCFG memory devices exhibit a low threshold voltage (<3 V), large memory window (66 V), stable endurance (>100 cycles), and long-term retention (>10 years). This study provides universal guidance for printing functional coatings and multi-layer devices.

A potassium-chloride co-transporter with altered genome architecture functions as a suppressor in glioma.

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.

MiR-4763-3p accelerates lipopolysaccharide-induced cardiomyocyte apoptosis and inflammatory response by targeting IL10RA.

In order to investigate miR-4763-3p and associated genes' roles in myocarditis, AC16 cell line was divided into LPS + miR-4763-3p inhibitor, LPS + NC inhibitor, LPS + miR-4763-3p inhibitor + si-IL10RA and NC groups, and Q-PCR was used to find out whether miR-4763-3p was expressed; Targetscan, Genecards, and MiRDB were used to estimate the miR-4763-3p target; Targetscan was used to display binding sites. Western blot assay was undertaken to detect Bax, Bcl-2, and IL10RA expression. Proliferation and apoptosis were processed using CCK8 and the flow cytometry assay, respectively. Migration and invasion were confirmed utilizing Transwell test. ELISA assay was processed to show the content of IL-6, IL-1ß, IL-10 and TGF-ß in the cell culture supernatant. After being exposed to LPS, cardiomyocyte cells expressed more miR-4763-3p. MiR-4763-3p inhibitor accelerated proliferation, migration and invasion behavior, while it also decreased apoptosis rate in LPS-treated cardiomyocyte cells. MiR-4763-3p inhibitor attenuated the inflammatory response by up-regulating Bax expression and down-regulating Bcl-2 level in LPS-treated cardiomyocyte cells. In cardiomyocyte cells treated with LPS, MiR-4763-3p expression was elevated. si-IL10RA The miR-4763-3p inhibitor restored its effects. MiR-4763-3p accelerates lipopolysaccharide-induced cardiomyocyte apoptosis and inflammatory response by targeting IL10RA, which might be a potential target for myocarditis.

Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage.

OBJECTIVE: Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury. METHODS: We established an AKI mouse model by intraperitoneal injection of cisplatin in vivo, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR. RESULTS: Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage in vitro. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated. CONCLUSION: Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI.

A personalized multitasking framework for real-time prediction of blood glucose levels in type 1 diabetes patients.

Real-time prediction of blood glucose levels (BGLs) in individuals with type 1 diabetes (T1D) presents considerable challenges. Accordingly, we present a personalized multitasking framework aimed to forecast blood glucose levels in patients. The patient data was initially categorized according to gender and age and subsequently utilized as input for a modified GRU network model, creating five prediction sub-models. The model hyperparameters were optimized and tuned after introducing the decay factor and incorporating the TCN network and attention mechanism into the GRU model. This step was undertaken to improve the capability of feature extraction. The Ohio T1DM clinical dataset was used to train and evaluate the performance of the proposed model. The metrics, including Root Mean Square Error (RMSE), Mean Absolute Error (MAE) and Clark Error Grid Analysis (EGA), were used to evaluate the performance. The results showed that the average RMSE and the MAE of the proposed model were 16.896 and 9.978 mg/dL, respectively, over the prediction horizon (PH) of 30 minutes. The average RMSE and the MAE were 28.881 and 19.347 mg/dL, respectively, over the PH of 60 min. The proposed model demonstrated excellent prediction accuracy. In addition, the EGA analysis showed that the proposed model accurately predicted 30-minute and 60-minute PH within zones A and B, demonstrating that the framework is clinically feasible. The proposed personalized multitask prediction model in this study offers robust assistance for clinical decision-making, playing a pivotal role in improving the outcomes of individuals with diabetes.

Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.

Right congenital pyriform sinus fistula.

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A Transferability-Based Method for Evaluating the Protein Representation Learning.

Self-supervised pre-trained language models have recently risen as a powerful approach in learning protein representations, showing exceptional effectiveness in various biological tasks, such as drug discovery. Amidst the evolving trend in protein language model development, there is an observable shift towards employing large-scale multimodal and multitask models. However, the predominant reliance on empirical assessments using specific benchmark datasets for evaluating these models raises concerns about the comprehensiveness and efficiency of current evaluation methods. Addressing this gap, our study introduces a novel quantitative approach for estimating the performance of transferring multi-task pre-trained protein representations to downstream tasks. This transferability-based method is designed to quantify the similarities in latent space distributions between pre-trained features and those fine-tuned for downstream tasks. It encompasses a broad spectrum, covering multiple domains and a variety of heterogeneous tasks. To validate this method, we constructed a diverse set of protein-specific pre-training tasks. The resulting protein representations were then evaluated across several downstream biological tasks. Our experimental results demonstrate a robust correlation between the transferability scores obtained using our method and the actual transfer performance observed. This significant correlation highlights the potential of our method as a more comprehensive and efficient tool for evaluating protein representation learning.

Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients.

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.