Dysregulated Wnt/ß-catenin signaling confers resistance to cuproptosis in cancer cells.

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

The relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and hyperuricaemia.

PURPOSE: The ratio of non-high-density lipoprotein cholesterol (non-HDL-c) to high-density lipoprotein cholesterol (HDL-c) (NHHR) is a novel comprehensive lipid index. The aim of this study was to investigate the relationship between the NHHR and the prevalence of hyperuricaemia (HUA) in the adult population of the U.S. METHODS: This cross-sectional study collected data from the National Health and Nutrition Examination Survey (NHANES) (2007-2018). HUA was defined as a serum uric acid (SUA) concentration ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Multivariate logistic regression models and the restricted cubic spline (RCS) method were applied to examine the relationship between the NHHR and the risk of developing HUA. Subgroup analyses and interaction tests were also performed. RESULTS: The prevalence of HUA increased with increasing NHHR values (9.01% vs. 13.38% vs. 17.31% vs. 25.79%, P < 0.001). The NHHR was independently correlated with the risk of developing HUA (OR = 1.10, 95% CI: 1.05-1.16; P < 0.001). Furthermore, the risk of developing HUA was significantly greater among individuals with the highest NHHR quartile than among those with the lowest NHHR quartile (OR = 1.94, 95% CI: 1.62-2.33; P < 0.001). This relationship was consistent across subgroups. According to the RCS analysis, an inverted U-shaped relationship existed between the NHHR and the risk of developing HUA. CONCLUSIONS: The NHHR was closely associated with an increased risk of developing HUA. Further studies on the NHHR could be beneficial for preventing and treating HUA.

QTL mapping and genomic selection of stem and branch diameter in soybean (Glycine max L.).

Introduction: Soybean stem diameter (SD) and branch diameter (BD) are closely related traits, and genetic clarification of SD and BD is crucial for soybean breeding. Methods: SD and BD were genetically analyzed by a population of 363 RIL derived from the cross between Zhongdou41 (ZD41) and ZYD02878 using restricted two-stage multi-locus genome-wide association, inclusive composite interval mapping, and three-variance component multi-locus random SNP effect mixed linear modeling. Then candidate genes of major QTLs were selected and genetic selection model of SD and BD were constructed respectively. Results and discussion: The results showed that SD and BD were significantly correlated (r = 0.74, P < 0.001). A total of 93 and 84 unique quantitative trait loci (QTL) were detected for SD and BD, respectively by three different methods. There were two and ten major QTLs for SD and BD, respectively, with phenotypic variance explained (PVE) by more than 10%. Within these loci, seven genes involved in the regulation of phytohormones (IAA and GA) and cell proliferation and showing extensive expression of shoot apical meristematic genes were selected as candidate genes. Genomic selection (GS) analysis showed that the trait-associated markers identified in this study reached 0.47-0.73 in terms of prediction accuracy, which was enhanced by 6.56-23.69% compared with genome-wide markers. These results clarify the genetic basis of SD and BD, which laid solid foundation in regulation gene cloning, and GS models constructed could be potentially applied in future breeding programs.

Non-nitrogen-containing bisphosphonates and nitrogen-containing bisphosphonates for the treatment of atherosclerosis and vascular calcification: A meta-analysis.

BACKGROUND: The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular calcification (VC) is uncertain. This meta-analysis was conducted to evaluate the efficacy of non-N-BPs and N-BPs in the treatment of AS and VC. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from their inception to July 5th, 2023. Eligible studies comparing bisphosphonates (BPs) versus no BPs in the treatment of AS and VC were included. The data were analyzed using Review Manager Version 5.3. RESULTS: Seventeen studies were included in this meta-analysis. Twelve were randomized control trials (RCTs), and 5 were nonrandomized studies. Overall, 813 patients were included in the BPs group, and 821 patients were included in the no BPs group. Compared with no BP treatment, non-N-BP or N-BP treatment did not affect serum calcium (P > .05), phosphorus (P > .05) or parathyroid hormone (PTH) levels (P > .05). Regarding the effect on serum lipids, non-N-BPs decreased the serum total cholesterol (TC) level (P < .05) and increased the serum triglyceride (TG) level (P < .01) but did not affect the serum low-density lipoprotein cholesterol (LDL-C) level (P > .05). N-BPs did not affect serum TC (P > .05), TG (P > .05) or LDL-C levels (P > .05). Regarding the effect on AS, non-N-BPs did not have a beneficial effect (P > .05). N-BPs had a beneficial effect on AS, including reducing the intima-media thickness (IMT) (P < .05) and plaque area (P < .01). For the effect on VC, non-N-BPs had a beneficial effect (P < .01), but N-BPs did not have a beneficial effect (P > .05). CONCLUSION: Non-N-BPs and N-BPs did not affect serum calcium, phosphorus or PTH levels. Non-N-BPs decreased serum TC levels and increased serum TG levels. N-BPs did not affect serum lipid levels. Non-N-BPs had a beneficial effect on VC, and N-BPs had a beneficial effect on AS.

Association between monocyte to high-density lipoprotein cholesterol ratio and kidney stone: insights from NHANES.

Purpose: The ratio of monocyte to high-density lipoprotein cholesterol (MHR) has surfaced as a novel biomarker indicative of inflammation and oxidative stress. The aim of our study was to evaluate the association between MHR and the risk of kidney stones. Methods: This study analyzed data from individuals aged 20-79 who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The MHR was assessed as the exposure variable, while a self-reported history of kidney stones was used as the outcome variable. The independent relationship between MHR and the risk of kidney stones was thoroughly evaluated. Results: This study included 28,878 participants, and as the quartile range of the MHR increased, the proportion of kidney stones also rose progressively (7.20% to 8.89% to 10.88% to 12.05%, P<0.001). After adjusting for confounding factors, MHR was independently associated with an increased risk of kidney stones (OR=1.31, 95%CI=1.11-1.54, P=0.001), also independent of some common inflammatory indices. Subgroup analysis suggested that the relationship between MHR and kidney stones was more pronounced in female and individuals aged 20-49. Further restricted cubic spline (RCS) analysis indicated a nonlinear relationship between MHR and the risk of kidney stones. Conclusion: Our results indicate a positive correlation between MHR and an increased risk of kidney stones in US adults, underscoring the need for further large-scale prospective cohort studies to validate these findings.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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%.

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.