Reduced sensitivity to thyroid hormones is associated with lung function in euthyroid individuals.

Background: The thyroid gland exhibits a subtle interconnection with the lungs. We further investigated the correlation between thyroid hormone sensitivity and lung function in euthyroid individuals. Methods: Data on spirometry and mortality for participants aged 19-79 years were extracted from the NHANES database. Obstructive lung function was defined as a forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) < 0.70, while restrictive lung function was considered when FEV1/FVC ≥0.70 and baseline FVC <80 % predicted. Central and peripheral sensitivities to thyroid hormones were mainly evaluated by Thyroid Feedback Quantile-based Index (TFQI) and Free Triiodothyronine/Free thyroxine (FT3/FT4) ratio. Logistic regression and subgroup analysis were used to examine potential associations between thyroid hormone sensitivity and lung function. The association between TFQI and all-cause mortality risk was also investigated. Results: A total of 6539 participants were analyzed, 900 with obstructive lung function and 407 with restrictive lung function. The prevalence of impaired lung function, both obstructive and restrictive, increased with higher TFQI levels. Logistic regression analysis showed that increased TFQI and decreased FT3/FT4 levels were independent risk factors for obstructive and restrictive lung function (P < 0.05). After adjusting for the impact of lung function, TFQI (HR = 1.25, 95 % CI 1.00-1.56, P = 0.048) was an independent risk factor for all-cause mortality. Conclusion: Reduced sensitivity to thyroid hormones has been linked to impaired lung function. TFQI and FT3/FT4 are potential epidemiological tools to quantify the role of central and peripheral thyroid resistance in lung function.

m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling.

N1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.

Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity.

Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.

The relationship between weight-adjusted-waist index and diabetic kidney disease in patients with type 2 diabetes mellitus.

Purpose: Obesity, particularly abdominal obesity, is seen as a risk factor for diabetic complications. The weight-adjusted-waist index (WWI) is a recently developed index for measuring adiposity. Our goal was to uncover the potential correlation between the WWI index and diabetic kidney disease (DKD) risk. Methods: This cross-sectional study included adults with type 2 diabetes mellitus (T2DM) who participated in the NHANES database (2007-2018). The WWI index was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). DKD was diagnosed based on impaired estimated glomerular filtration rate (eGFR<60 mL/min/1.73m2), albuminuria (urinary albumin to urinary creatinine ratio>30 mg/g), or both in T2DM patients. The independent relationship between WWI index and DKD risk was evaluated. Results: A total of 5,028 participants with T2DM were included, with an average WWI index of 11.61 ± 0.02. As the quartile range of the WWI index increased, the prevalence of DKD gradually increased (26.76% vs. 32.63% vs. 39.06% vs. 42.96%, P<0.001). After adjusting for various confounding factors, the WWI index was independently associated with DKD risk (OR=1.32, 95%CI:1.12-1.56, P<0.001). The area under the ROC curve (AUC) of the WWI index was higher than that of body mass index (BMI, kg/m2) and WC. Subgroup analysis suggested that the relationship between the WWI index and DKD risk was of greater concern in patients over 60 years old and those with cardiovascular disease. Conclusions: Our findings suggest that higher WWI levels are linked to DKD in T2DM patients. The WWI index could be a cost-effective and simple way to detect DKD, but further prospective studies are needed to confirm this.

Association Between Remnant Cholesterol and Risk of Hyperuricemia: A Cross-Sectional Study.

Remnant cholesterol (RC) is closely related to metabolic diseases. Our study aims to explore the relationship between RC and hyperuricemia. This cross-sectional study included 14 568 adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018 in the United States. RC is calculated by subtracting high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) from total cholesterol (TC). Hyperuricemia is defined by serum uric acid (SUA) levels≥7 mg/dl in men and≥6 mg/dl in women. The independent association between RC and hyperuricemia was evaluated. As the quartile range of RC levels increases, the prevalence of hyperuricemia also rises (7.84% vs. 13.71% vs. 18.61% vs. 26.24%, p<0.001). After adjusting for confounding factors, the fourth quartile of RC was associated with an increased risk of hyperuricemia compared with the first quartile (OR=2.942, 95% CI 2.473-3.502, p<0.001). Receiver Operating Characteristic (ROC) analysis shows that RC outperforms other single lipid indices in hyperuricemia. Further Restricted Cubic Splines (RCS) analysis suggests a nonlinear relationship between RC levels and hyperuricemia. Elevated RC levels were found to be linked to hyperuricemia. Further studies on RC hold promise for both preventing and addressing hyperuricemia.

Physical mechanism-corrected degradation trend prediction network under data missing.

Accurate degradation trend prediction (DTP) is crucial for optimizing equipment operation and maintenance, thereby boosting production efficiency. This study introduces a novel Data Repair and Dual-data-stream LSTM (DR-DLSTM) network to tackle the challenge of missing data in equipment DTP. The proposed DR-DLSTM framework employs convex optimization to consider both the trend and periodic variations in the data, incorporating polynomial and trigonometric functions into the implicit feature matrix to construct latent vectors for missing data rectification. The network features a Dual-LSTM block with dual data streams to enhance feature extraction, with two gating update units correlating time series components and redistributing feature weights. The Dual-LSTM enables separate and accurate prediction of trend and periodic components, thereby enhancing the feature extraction capability of the prediction model. Additionally, the integration of physical rule information through Fourier and wavelet transform frequency correction modules allows for dynamic adjustments in prediction outcomes, from global trends to localized details. The DR-DLSTM's effectiveness is demonstrated through comprehensive comparisons with state-of-the-art models across multiple datasets, highlighting its superior performance. The results demonstrate the superiority of the proposed model. These algorithms were implemented in Python using Torch on a 2.9 GHz Intel I7 CPU and TITAN Xp GPU.

Glutamine inhibition combined with CD47 blockade enhances radiotherapy-induced ferroptosis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a formidable cancer type that poses significant treatment challenges, including radiotherapy (RT) resistance. The metabolic characteristics of tumors present substantial obstacles to cancer therapy, and the relationship between RT and tumor metabolism in HNSCC remains elusive. Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Here, we report that after RT, glutamine levels rise in HNSCC, and the glutamine transporter protein SLC1A5 is upregulated. Notably, blocking glutamine significantly enhances the therapeutic efficacy of RT in HNSCC. Furthermore, inhibition of glutamine combined with RT triggers immunogenic tumor ferroptosis, a form of nonapoptotic regulated cell death. Mechanistically, RT increases interferon regulatory factor (IRF) 1 expression by activating the interferon signaling pathway, and glutamine blockade augments this efficacy. IRF1 drives transferrin receptor expression, elevating intracellular Fe2+ concentration, disrupting iron homeostasis, and inducing cancer cell ferroptosis. Importantly, the combination treatment-induced ferroptosis is dependent on IRF1 expression. Additionally, blocking glutamine combined with RT boosts CD47 expression and hinders macrophage phagocytosis, attenuating the treatment effect. Dual-blocking glutamine and CD47 promote tumor remission and enhance RT-induced ferroptosis, thereby ameliorating the tumor microenvironment. Our work provides valuable insights into the metabolic and immunological mechanisms underlying RT-induced ferroptosis, highlighting a promising strategy to augment RT efficacy in HNSCC.

The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis.

BACKGROUND: We aimed to explore the causal relationship between blood metabolites and the risk of visceral obesity, as measured by visceral adipose tissue (VAT). METHODS: Summary statistics for 486 blood metabolites and total, as well as sex-stratified, MRI-derived VAT measurements, adjusted for body mass index (BMI) and height, were collected from previous genome-wide association studies (GWAS). A two-sample Mendelian Randomization (MR) design was used. Comprehensive evaluation was further conducted, including sensitivity analysis, linkage disequilibrium score (LDSC) regression, Steiger test, and metabolic pathway analysis. RESULTS: After multiple testing correction, arachidonate (20:4n6) has been implicated in VAT accumulation (ß = 0.35, 95%CI:0.18-0.52, P < 0.001; FDR = 0.025). Additionally, several blood metabolites were identified as potentially having causal relationship (FDR < 0.10). Among them, lysine (ß = 0.67, 95%CI: 0.28-1.06, P < 0.001; FDR = 0.074), proline (ß = 0.30, 95%CI:0.13-0.48, P < 0.001; FDR = 0.082), valerate (ß = 0.50, 95%CI:0.23-0.78, P < 0.001, FDR = 0.091) are associated with an increased risk of VAT accumulation. On the other hand, glycine (ß=-0.21, 95%CI: -0.33-0.09), P < 0.001, FDR = 0.076) have a protective effect against VAT accumulation. Most blood metabolites showed consistent trends between different sexes. Multivariable MR analysis demonstrated the effect of genetically predicted arachidonate (20:4n6) and proline on VAT remained after accounting for BMI and glycated hemoglobin (HbA1c). There is no evidence of heterogeneity, pleiotropy, and reverse causality. CONCLUSION: Our MR findings suggest that these metabolites may serve as biomarkers, as well as for future mechanistic exploration and drug target selection of visceral obesity.

Full thermal ablation versus partial thermal ablation for secondary hyperparathyroidism: A meta-analysis.

BACKGROUND: Regarding the thermal ablation treatment of refractory secondary hyperparathyroidism (SHPT), there is no consensus on the ablation range of the hyperplastic parathyroid gland. Therefore, this meta-analysis was conducted to evaluate the efficacy and complications between full and partial thermal ablation in patients with refractory SHPT. METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang databases were searched from inception to July 1, 2023. Eligible studies comparing full thermal ablation and partial thermal ablation for SHPT were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Four studies were included in the meta-analysis. Three cohort studies and one randomized controlled trial involving 62 patients in the full thermal ablation group and 63 patients in the partial thermal ablation group were included. The serum parathyroid hormone (PTH), calcium, and phosphorus levels after full ablation were all lower than those after partial ablation (P < .05). There was no significant difference between the partial and full ablation groups concerning the incidence rate of severe hypocalcemia (P = .09). There was no significant difference between the partial and full ablation groups concerning symptom improvement, including bone joint pain, itching, and myasthenia (P < .05). CONCLUSION: Full ablation was superior to partial ablation in terms of reducing PTH, calcium and phosphorus levels. Full ablation might not significantly increase the incidence of severe hypocalcemia. Larger multicentre randomized controlled trials are necessary to confirm the conclusion.

Synthesis of component-controllable monolayer MoxW(1-x)S2ySe2(1-y) alloys with continuously tunable band gap and carrier type.

Alloying can effectively modify electronic and optical properties of two-dimensional (2D) transition metal dichalcogenides (TMDs). However, efficient and simple methods to synthesize atomically thin TMD alloys need to be further developed. In this study, we synthesized 25 monolayer MoxW(1-x)S2ySe2(1-y) alloys by using a new liquid phase edge epitaxy (LPEE) growth method with high controllability. This straightforward approach can be used to obtain monolayer materials and operates on a self-limiting growth mechanism. The process allows the liquid solution to come into contact with the two-dimensional grains only at their edges, resulting in epitaxy confined only along the in-plane direction, which produces exclusively monolayer epitaxy. By controlling the weight ratio of MoS2/WSe2 (MoSe2/WS2), 25 monolayer MoxW(1-x)S2ySe2(1-y) alloys with different atomic ratios can be obtained on sapphire substrates, with band gap ranging from WS2 (1.55 eV) to MoSe2 (1.99 eV) and a continuously broad spectrum ranging from 623 nm to 800 nm. By adjusting the alloy composition, the carrier type and carrier mobility of alloy-based field-effect transistors can be modulated. In particular, the adjustable conductivity of MoxW(1-x)S2ySe2(1-y) alloys from n-type to bipolar type is achieved for the first time. This general synthetic strategy provides a foundation for the development of monolayer TMD alloys with multiple components and various 2D materials.

Synergetic Effect and Phase Engineering by Formation of Ti3C2Tx Modified 2H/1T-MoSe2 Composites for Enhanced HER.

The typical semi conductivity and few active sites of hydrogen evolution of 2H MoSe2 severely restrict its electrocatalytic hydrogen evolution performance. At the same time, the 1T MoSe2 has metal conductivity and plentiful hydrogen evolution sites, making it feasible to optimize the electrocatalytic hydrogen evolution behavior of MoSe2 using phase engineering. In this study, we, through a simple one-step hydrothermal method, composed 1T/2H MoSe2, and then used newly emerging transition metal carbides with several atomic-layer thicknesses Ti3C2Tx to improve the conductivity of a MoSe2-based electrocatalyst. Finally, MoSe2@Ti3C2Tx was successfully synthesized, according to the control of the additional amount of Ti3C2Tx, to form a proper MoSe2/ Ti3C2Tx heterostructure with a better electrochemical HER performance. As obtained MoSe2@4 mg-Ti3C2Tx achieved a low overpotential, a small Tafel slope and this work offers additional insight into broadened MoSe2 and MXenes-based catalyst's electrochemical application.

QTL Mapping of Soybean (Glycine max) Vine Growth Habit Trait.

The vine growth habit (VGH) is a notable property of wild soybean plants that also holds a high degree of importance in domestication as it can preclude using these wild cultivars for breeding and improving domesticated soybeans. Here, a bulked segregant analysis (BSA) approach was employed to study the genetic etiology of the VGH in soybean plants by integrating linkage mapping and population sequencing approaches. To develop a recombinant inbred line (RIL) population, the cultivated Zhongdou41 (ZD41) soybean cultivar was bred with ZYD02787, a wild soybean accession. The VGH status of each line in the resultant population was assessed, ultimately leading to the identification of six and nine QTLs from the BSA sequencing of the F4 population and F6-F8 population sequence mapping, respectively. One QTL shared across these analyzed generations was detected on chromosome 19. Three other QTLs detected by BSA-seq were validated and localized to the 90.93 kb, 2.9 Mb, and 602.08 kb regions of chromosomes 6 and 13, harboring 14, 53, and 4 genes, respectively. Three consistent VGH-related QTLs located on chromosomes 2 and 19 were detected in a minimum of three environments, while an additional six loci on chromosomes 2, 10, 13, and 18 were detected in at least two environments via ICIM mapping. Of all the detected loci, five had been reported previously whereas seven represent novel QTLs. Together, these data offer new insights into the genetic basis of the VGH in soybean plants, providing a rational basis to inform the use of wild accessions in future breeding efforts.

VISTA blockade alleviates immunosuppression of MDSCs in oral squamous cell carcinoma.

V-domain Ig suppressor of T-cell activation (VISTA) is a novel immune checkpoint regulator that can inhibit T cell-mediated antitumor immunity. Although the use of anti-VISTA monoclonal antibody has demonstrated encouraging outcomes in the therapy of various malignancies, its specific impact and underlying mechanisms in oral squamous cell carcinoma (OSCC) remain to be explored. In this work, we analyzed human OSCC tissue microarrays, human peripheral blood mononuclear cells, and immunocompetent transgenic mouse models to investigate the relationship between high VISTA expression and markers of myeloid-derived immunosuppressive cells (MDSCs; CD11b, CD33, Arginase-1), tumor-associated macrophages (CD68, CD163, CD206), and T cell function (CD8, PD-L1, Granzyme B). In OSCC, we discovered that VISTA was highly expressed and stably expressed in MDSCs. Furthermore, we established a mouse OSCC orthotopic xenograft tumor model to investigate the impact of VISTA blockade on the tumor microenvironment. We found that VISTA blockade reduces the immunosuppressive microenvironment and delays tumor growth. This is achieved by suppressing the quantity and function of MDSCs while boosting the function of tumor-infiltrating T cells. Our research indicated that VISTA expressed by MDSCs has a crucial function in the progression of OSCC and that VISTA blockade therapy is a promising immune checkpoint blockade therapy.

The relationship between triglyceride-glucose index and albuminuria in United States adults.

Purpose: Triglyceride-glucose (TyG) index is a simple and reliable indicator of metabolic dysfunction. We aimed to investigate a possible relationship between TyG index and albuminuria in the United States adult population. Methods: This cross-sectional study was conducted among adults with complete TyG index and urinary albumin/urinary creatinine (UACR) from 2011-2018 National Health and Nutrition Examination Survey (NHANES). The independent relationship between TyG index and albuminuria (UACR>30mg/g) was evaluated. TyG index was compared with insulin resistance represented by homeostatic model assessment of insulin resistance (HOMA-IR), and metabolic syndrome. Subgroup analysis was also performed. Results: A total of 9872 participants were included in this study, and the average TyG index was 8.53 ± 0.01. The proportion of albuminuria gradually increased with the increase of TyG index quartile interval. Elevated TyG index was independently associated with albuminuria, and this association persisted after additional adjustments for HOMA-IR or dichotomous metabolic syndrome. The area under the ROC curve (AUC) of TyG index was larger than that of log (HOMA-IR). Subgroup analysis suggested that the relationship between TyG index and albuminuria is of greater concern in age<60, overweight/obese, diabetic, and metabolic syndrome patients. Conclusion: The TyG index may be a potential epidemiological tool to quantify the role of metabolic dysfunction, rather than just insulin resistance, in albuminuria in the United States adult population. Further large-scale prospective studies are needed to confirm our findings.

Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy.

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%.

Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.

COVID-19 vaccination effectiveness and safety in vulnerable populations: a meta-analysis of 33 observational studies.

Background: Even 3 years into the COVID-19 pandemic, questions remain about how to safely and effectively vaccinate vulnerable populations. A systematic analysis of the safety and efficacy of the COVID-19 vaccine in at-risk groups has not been conducted to date. Methods: This study involved a comprehensive search of PubMed, EMBASE, and Cochrane Central Controlled Trial Registry data through 12 July 2022. Post-vaccination outcomes included the number of humoral and cellular immune responders in vulnerable and healthy populations, antibody levels in humoral immune responders, and adverse events. Results: A total of 23 articles assessing 32 studies, were included. The levels of IgG (SMD = -1.82, 95% CI [-2.28, -1.35]), IgA (SMD = -0.37, 95% CI [-0.70, -0.03]), IgM (SMD = -0.94, 95% CI [-1.38, -0.51]), neutralizing antibodies (SMD = -1.37, 95% CI [-2.62, -0.11]), and T cells (SMD = -1.98, 95% CI [-3.44, -0.53]) were significantly lower in vulnerable than in healthy populations. The positive detection rates of IgG (OR = 0.05, 95% CI [0.02, 0.14]) and IgA (OR = 0.03, 95% CI [0.01, 0.11]) antibodies and the cellular immune response rates (OR = 0.20, 95% CI [0.09, 0.45]) were also lower in the vulnerable populations. There were no statistically significant differences in fever (OR = 2.53, 95% CI [0.11, 60.86]), chills (OR = 2.03, 95% CI [0.08, 53.85]), myalgia (OR = 10.31, 95% CI [0.56, 191.08]), local pain at the injection site (OR = 17.83, 95% CI [0.32, 989.06]), headache (OR = 53.57, 95% CI [3.21, 892.79]), tenderness (OR = 2.68, 95% CI [0.49, 14.73]), and fatigue (OR = 22.89, 95% CI [0.45, 1164.22]) between the vulnerable and healthy populations. Conclusion: Seroconversion rates after COVID-19 vaccination were generally worse in the vulnerable than healthy populations, but there was no difference in adverse events. Patients with hematological cancers had the lowest IgG antibody levels of all the vulnerable populations, so closer attention to these patients is recommended. Subjects who received the combined vaccine had higher antibody levels than those who received the single vaccine.

Dual-frequency enhanced attention network for aircraft engine remaining useful life prediction.

Accurately evaluating the remaining useful life (RUL) of aircraft engines is crucial for ensuring operational safety and reliability, and serves as a critical foundation for making informed maintenance decisions. In this paper, a novel prediction framework is proposed for forecasting the RUL of engines, which utilizes a dual-frequency enhanced attention network architecture built upon separable convolutional neural networks. First, the information volume criterion (IVC) index and information content threshold (CIT) equation are designed, which are applied to quantitatively quantify the degradation features of the sensor and remove redundant information. In addition, this paper introduces two trainable frequency-enhanced modules, namely the Fourier transform module (FMB-f) and the wavelet transform module (FMB-w), to incorporate physical rules information into the prediction framework, dynamically capture the global trend and local details of the degradation index, and further improve the prediction performance and robustness of the prediction model. Furthermore, the proposed efficient channel attention block generates a unique set of weights for each possible vector sample, which establishes the interdependence among different sensors, thereby augmenting the prediction stability and precision of the framework. The experimental demonstrate that the proposed RUL prediction framework can deliver accurate RUL predictions.

LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3ß degradation in head and neck squamous cell carcinoma.

Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3ß, which in turn facilitates nuclear translocation of ß-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.

Identification of Basement Membrane Genes and Related Molecular Subtypes in Nonalcoholic Fatty Liver Disease.

Basement membranes (BMs) are widely distributed and highly specialized extracellular matrix (ECM). The goal of this study was to explore novel genes associated with nonalcoholic fatty liver disease (NAFLD) from the perspective of BMs. Sequencing results of 304 liver biopsy samples about NAFLD were systematically obtained from the Gene Expression Omnibus (GEO) database. Biological changes during NAFLD progression and hub BM-associated genes were investigated by differential gene analysis and weighted gene co-expression network analysis (WGCNA), respectively. The nonalcoholic steatohepatitis (NASH) subgroups were identified based on hub BM-associated genes expression, as well as the differences in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and immune microenvironment between different subgroups were compared. Extracellular matrix (ECM) seems to play an important role in the development of NAFLD. Three representative BM-associated genes (ADAMTS2, COL5A1, and LAMC3) were finally identified. Subgroup analysis results suggested that there were significant changes in KEGG signaling pathways related to metabolism, extracellular matrix, cell proliferation, differentiation, and death. There were also changes in macrophage polarization, neutrophils, and dendritic cells abundance, and so on. In conclusion, the present study identified novel potential BM-associated biomarkers and further explored the heterogeneity of NASH that might provide new insights into the diagnosis, assessment, management, and personalized treatment of NAFLD.