CXCL10 could be a prognostic and immunological biomarker in bladder cancer.

INTRODUCTION: As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. METHOD: In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. RESULTS: We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. CONCLUSION: Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA.

Nomogram for predicting the risk of postoperative delirium in elderly patients undergoing orthopedic surgery.

OBJECTIVE: To retrospectively analyze the risk factors for postoperative delirium (POD) after orthopedic surgery in elderly patients and establish an individualized nomogram to predict the risk of POD. METHODS: The data of 1011 patients who underwent orthopedic surgery from January 2019 to January 2022 were retrospectively analyzed. Univariate and multivariate logistic analyses were used to screen for independent risk factors. Stepwise regression was conducted to screen risk factors to construct a nomogram to predict the risk of POD after orthopedic surgery in elderly individuals, and nomogram validation analyses were performed. RESULTS: The logistic regression results showed that age (≥ 75 years old vs. < 75 years old; odds ratio (OR) = 2.889; 95% confidence interval (CI), 1.149, 7.264), sex (male vs. female, OR = 2.368; 95% CI, 1.066, 5.261), and preoperative cognitive impairment (yes vs. no, OR = 13.587; 95% CI, 4.360, 42.338) were independent risk factors for POD in elderly patients who underwent orthopedic surgery (P < 0.05). A nomogram was constructed using 7 risk factors, i.e., age, American Society of Anesthesiologists (ASA) classification, sex, preoperative hemoglobin (Hb), preoperative pulmonary disease, cognitive impairment, and intraoperative infusion volume. The area under the curve (AUC) showed good discrimination (0.867), the slope of the calibration curve was 1.0, and the optimal net benefit of the nomogram from the decision curve analysis (DCA) was 0.01-0.58. CONCLUSION: This study used 7 risk factors to construct a nomogram to predict the risk of POD after major orthopedic surgery in elderly individuals, and the nomogram had good discrimination ability, accuracy, and clinical practicability.

Metabonomics and pharmacodynamics studies of Gentiana radix and wine-processed Gentiana radix in damp-heat jaundice syndrome rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana radix (GR) and wine-processed Gentiana radix (WGR) have been commonly used in folk medicine for the treatment of bile or liver disorders, including jaundice, hepatitis, swelling and inflammation for thousands of years. However, the therapeutic effects of gentian root (GR) and wine-made gentian root (WGR) treatment on damp-heat jaundice syndrome (DHJS) have not been studied in animal experiments. AIM OF THE STUDY: This study aimed to investigate the protective effects and mechanisms of GR and WGR on DHJS in rats. MATERIALS AND METHODS: In a high-fat and high-sugar diet in a humidified hot environment, hepatic injury induced by giving alpha-naphthalene isothiocyanate (ANIT) in rats were used as a DHJS model. Histological analysis, enzyme-linked immunosorbent assay (ELISA), PCR analysis, and metabolomics were used to elucidate the mechanism of GR and WGR for DHJS. RESULTS: The results indicated that GR and WGR affected DHJS by inhibiting the release of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (D-BIL), total bilirubin (TBIL), total bile acid (TBA), malondialdehyde (MDA), glutathione S-transferase (GST) (P < 0.05). In addition, they significantly reduced the gene expression levels of Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BESP), multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) (P < 0.05). The WGR group improved the above function indicators better than the GR group. GR and WGR could restore 11 potential biomarkers in rats with DHJS tended to return to normal levels, these biomarkers were involved in arachidonic acid metabolism, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, porphyrin and chlorophyll metabolism, retinol metabolism, arginine biosynthesis. The results of the metabolic pathway showed that WGR was significantly better than GR in the improvement of porphyrin and chlorophyll metabolism. CONCLUSIONS: These findings suggest that treatment with GR and WGR has a beneficial effect on DHJS in rats, the major mechanisms may be involved in improving functional indicators of the body and endogenous metabolism, and WGR is more effective than GR. It provides important evidence for the clinical application of GR and WGR in the treatment of DHJS.

circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood-brain barrier integrity and cognitive function in uremic encephalopathy.

Uremic encephalopathy (UE) poses a significant challenge in neurology, leading to the need to investigate the involvement of non-coding RNA (ncRNA) in its development. This study employed ncRNA-seq and RNA-seq approaches to identify fundamental ncRNAs, specifically circRNA and miRNA, in the pathogenesis of UE using a mouse model. In vitro and in vivo experiments were conducted to explore the circRNA-PTPN4/miR-301a-3p/FOXO3 axis and its effects on blood-brain barrier (BBB) function and cognitive abilities. The research revealed that circRNA-PTPN4 binds to and inhibits miR-301a-3p, leading to an increase in FOXO3 expression. This upregulation results in alterations in the transcriptional regulation of ZO-1, affecting the permeability of human brain microvascular endothelial cells (HBMECs). The axis also influences the growth, proliferation, and migration of HBMECs. Mice with UE exhibited cognitive deficits, which were reversed by overexpression of circRNA-PTPN4, whereas silencing FOXO3 exacerbated these deficits. Furthermore, the uremic mice showed neuronal loss, inflammation, and dysfunction in the BBB, with the expression of circRNA-PTPN4 demonstrating therapeutic effects. In conclusion, circRNA-PTPN4 plays a role in promoting FOXO3 expression by sequestering miR-301a-3p, ultimately leading to the upregulation of ZO-1 expression and restoration of BBB function in mice with UE. This process contributes to the restoration of cognitive abilities.

Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Phosphorylated SHMT2 Regulates Oncogenesis Through m6A Modification in Lung Adenocarcinoma.

Targeting cancer-specific metabolic processes is a promising therapeutic strategy. Here, this work uses a compound library that directly inhibits metabolic enzymes to screen the potential metabolic targets in lung adenocarcinoma (LUAD). SHIN1, the specific inhibitor of serine hydroxymethyltransferase 1/2 (SHMT1/2), has a highly specific inhibitory effect on LUAD cells, and this effect depends mainly on the overexpression of SHMT2. This work clarifies that mitogen-activated protein kinase 1 (MAPK1)-mediated phosphorylation at Ser90 is the key mechanism underlying SHMT2 upregulation in LUAD and that this phosphorylation stabilizes SHMT2 by reducing STIP1 homology and U-box containing protein 1 (STUB1)-mediated ubiquitination and degradation. SHMT2-Ser90 dephosphorylation decreases S-adenosylmethionine levels in LUAD cells, resulting in reduced N6-methyladenosine (m6A) levels in global RNAs without affecting total protein or DNA methylation. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) analyses further demonstrate that SHMT2-Ser90 dephosphorylation accelerates the RNA degradation of oncogenic genes by reducing m6A modification, leading to the inhibition of tumorigenesis. Overall, this study elucidates a new regulatory mechanism of SHMT2 during oncogenesis and provides a theoretical basis for targeting SHMT2 as a therapeutic target in LUAD.

Functionalized lignin nanoparticles assembled with MXene reinforced polypropylene with favorable UV-aging resistance, electromagnetic shielding effects and superior fire-safety.

Deterioration in mechanical performances and aging resistance due to the introduction of flame retardants is a major obstacle for bio-based fire-safety polypropylene (PP). Herein, we reported a kind of functionalized lignin nanoparticles assembled with MXene (MX@LNP), and applied it to construct the flame-retardant PP composites (PP-MA) with superior fire safety, excellent mechanical performance, electromagnetic shielding effects and aging resistance. Specifically, the PP-MA doped with only 18 wt% flame-retardant additives (PP-MA18) achieved the UL-94 V-0 rating. In comparison to pure PP, PP-MA18 presented a greatly decreased peak of heat release rate (pHRR), total heat rate (THR), and peak smoke production rate (pSPR) by 79.7 %, 69.0 % and 75.8 %, respectively, and satisfactory decrease in total flammable and toxic volatiles evolved. The formed fine solid microstructure of carbon residuals effectively promoted the compactness of char layers. More importantly, the nano-effect and the strong interface interaction between the complexed MX@LNP and PP enhanced the tensile strength (45.78 MPa) and elongation at break (725.95 %) of PP-MA. Additionally, the significant ultraviolet absorption and electromagnetic wave dissipation performance of MXene and lignin enabled excellent aging resistance and electromagnetic shielding effects of PP-MA compared with PP. This achieved MX@LNP afforded a novel approach for developing flame retardant materials with excellent application performance.

Gene therapy corrects the neurological deficits of mice with sialidosis.

Patients with sialidosis (mucolipidosis type I) type I typically present with myoclonus, seizures, ataxia, cherry-red spots, and blindness because of mutations in the neuraminidase 1 (NEU1) gene. Currently, there is no treatment for sialidosis. In this study, we developed an adeno-associated virus (AAV)-mediated gene therapy for a Neu1 knockout (Neu1-/-) mouse model of sialidosis. The vector, AAV9-P3-NP, included the human NEU1 promoter, NEU1 cDNA, IRES, and CTSA cDNA. Untreated Neu1-/- mice showed astrogliosis and microglial LAMP1 accumulation in the nervous system, including brain, spinal cord, and dorsal root ganglion, together with impaired motor function. Coexpression of NEU1 and protective protein/cathepsin A (PPCA) in neonatal Neu1-/- mice by intracerebroventricular injection, and less effective by facial vein injection, decreased astrogliosis and LAMP1 accumulation in the nervous system and improved rotarod performance of the treated mice. Facial vein injection also improved the grip strength and survival of Neu1-/- mice. Therefore, cerebrospinal fluid delivery of AAV9-P3-NP, which corrects the neurological deficits of mice with sialidosis, could be a suitable treatment for patients with sialidosis type I. After intracerebroventricular or facial vein injection of AAV vectors, NEU1 and PPCA are expressed together. PPCA-protected NEU1 is then sent to lysosomes, where ß-Gal binds to this complex to form a multienzyme complex in order to execute its function.

Separation of high-purity plasma extracellular vesicles for investigating proteomic signatures in diabetic retinopathy.

Extracellular vesicles (EVs) play a multifaceted role in intercellular communication and hold significant promise as bio-functional indicators for clinical diagnosis. Although plasma samples represent one of the most critical sources of circulating EVs, the existing technical challenges associated with plasma-EV isolation have restricted their application in disease diagnosis and biomarker discovery. In this study, we introduce a two-step purification method utilizing ultracentrifugation (UC) to isolate crude extracellular vesicle (EV) samples, followed by a phospholipid affinity-based technique for the selective isolation of small EVs, ensuring a high level of purity for downstream proteomic analysis. Our research demonstrates that the UC & TiO2-coated magnetic bead (TiMB) purification system significantly improves the purity of EVs when compared to conventional UC or TiMB along. We further revealed that proteomic alterations in plasma EVs effectively reflect key gene ontology components associated with diabetic retinopathy (DR) pathogenesis, including the VEGF-activated neuropilin pathway, positive regulation of angiogenesis, angiogenesis, cellular response to vascular endothelial growth factor stimulus, and immune response. By employing a comprehensive analytical approach, which incorporates both time-series analysis (cluster analysis) and differential analysis, we have identified three potential protein signatures including LGALS3, MYH10, and CPB2 that closely associated with the retinopathy process. These proteins exhibit promising diagnostic and severity-classification capabilities for DR disease. This adaptable EV isolation system can be regarded as an effective analytical tool for enhancing plasma-based liquid biopsies toward clinical applications.

Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma.

Background: Abnormal coagulation is a common feature of glioma. There is a strong correlation between coagulation and the complement system, named complement and coagulation cascades (CCC). However, the role of CCC genes in lower-grade glioma (LGG) remains unclear. This study aimed to investigate the role of CCC genes in LGG. Methods: In total, 5,628 differential expressed genes were identified between 498 LGG tissues from The Cancer Genome Atlas (TCGA) and 207 normal brain tissues from Genotype-Tissue Expression Project (GTEx). Among them, 20 overlapped CCC genes were identified as differentially expressed CCC genes. Then, comprehensive bioinformatics analysis was used to investigate the role of CCC genes in LGG; 271 LGG tissues from the Chinese Glioma Genome Atlas (CGGA) were used as the validation dataset. Cell Counting Kit-8 (CCK8) proliferation assay, colony formation assay, and wound healing assay were conducted to explore the anti-glioma effect of the sensitive drugs we predicted. Results: We constructed a risk signature consisting of six CCC genes, including F2R, SERPINA1, TFPI, C1QC, C2, and C3AR1. The CCC gene-based risk signature could accurately predict the prognosis of patients with LGG. In addition, we found that the JAK-STAT, NOD-like receptor, Notch, PI3K-Akt, and Rap1 signaling pathways might be activated and had crosstalk with CCC in the high-risk group. Our findings analyses demonstrated that samples in high- and low-risk groups had different immune landscapes. Moreover, patients in the high-risk group might have greater resistance to immunotherapy. We validated the accuracy of the risk signature in predicting immunotherapy response in two public immunotherapy cohorts, GSE135222 and GSE78220. By means of oncoPredict, MG-132, BMS-536924, PLX-4720, and AZD6482 were identified as potential sensitive drugs for high-risk patients, of which MG-132 was particularly recommended for high-risk patients. We performed in vitro experiments to explore the anti-glioma effect of MG-132, and the results demonstrated MG-132 could inhibit the proliferation and migration of glioma cells. Conclusions: Our findings show that CCC genes are associated with the prognosis and immune infiltration of LGG and provide possible immunotherapeutic and novel chemotherapeutic strategies for patients with LGG based on the risk signature.

Injectable Microgels with Hybrid Exosomes of Chondrocyte-Targeted FGF18 Gene-Editing and Self-Renewable Lubrication for Osteoarthritis Therapy.

Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation of FGF18-based protein drugs is hindered by their short half-life, low delivery efficiency and the need for repeated articular injections. This study proposes a CRISPR/Cas9-based approach to effectively activate the FGF18 gene of OA chondrocytes at the genome level in vivo, using chondrocyte-affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18-hyEXO) loaded with an FGF18-targeted gene-editing tool. Furthermore, CAP/FGF18-hyEXO are encapsulated in methacrylic anhydride-modified hyaluronic (HAMA) hydrogel microspheres via microfluidics and photopolymerization to create an injectable microgel system (CAP/FGF18-hyEXO@HMs) with self-renewable hydration layers to provide persistent lubrication in response to frictional wear. Together, the injectable CAP/FGF18-hyEXO@HMs, combined with in vivo FGF18 gene editing and continuous lubrication, have demonstrated their capacity to synergistically promote cartilage regeneration, decrease inflammation, and prevent ECM degradation both in vitro and in vivo, holding great potential for clinical translation.

Micro-to-Nano Oncolytic Microbial System Shifts from Tumor Killing to Tumor Draining Lymph Nodes Remolding for Enhanced Immunotherapy.

Because the tumor-draining lymph nodes (TDLNs) microenvironment is commonly immunosuppressive, oncolytic microbe-induced tumor antigens aren't sufficiently cross-primed tumor specific T cells through antigen-presenting cells (e.g., dendritic cells (DCs)) in TDLNs. Herein, this work develops the micro-to-nano oncolytic microbial therapeutics based on pyranose oxidase (P2 O) overexpressed Escherichia coli (EcP) which are simultaneously encapsulated by PEGylated mannose and low-concentrated photosensitizer nanoparticles (NPs). Following administration, P2 O from this system generates toxic hydrogen peroxide for tumor regression and leads to the release of tumor antigens. The "microscale" EcP is triggered, following exposure to the laser irradiation, to secrete the "nanoscale" bacterial outer membrane vesicles (OMVs). The enhanced TDLNs delivery via OMVs significantly regulates the TDLNs immunomicroenvironment, promoting the maturation of DCs to potentiate tumor antigen-specific T cells immune response. The micro-to-nano oncolytic microbe is leveraged to exert tumor killing and remold TDLNs for initiating potent activation of DCs, providing promising strategies to facilitate microbial cancer vaccination.

A Noninvasive Circulating Signature of Combined Right Ventricular Pressure and Volume Overload in Tetralogy of Fallot/Pulmonary Atresia/Major Aortopulmonary Collateral Arteries.

Background: Despite surgical advances, children with tetralogy of Fallot/pulmonary atresia/major aortopulmonary collaterals (TOF/PA/MAPCAs) are subject to chronic right ventricular (RV) pressure and volume overload. Current diagnostic tools do not identify adverse myocardial remodeling and cannot predict progression to RV failure. We sought to identify a noninvasive, circulating signature of the systemic response to right heart stress to follow disease progression. Methods: Longitudinal data were collected from patients with TOF/PA/MAPCAs (N = 5) at the time of (1) early RV pressure overload and (2) late RV pressure and volume overload. Plasma protein and microRNA expression were evaluated using high-throughput data-independent mass spectroscopy and Agilent miR Microarray, respectively. Results: At the time of early RV pressure overload, median patient age was 0.34 years (0.02-9.37), with systemic RV pressures, moderate-severe hypertrophy, and preserved systolic function. Late RV pressure and volume overload occurred at a median age of 4.08 years (1.51-10.83), with moderate RV hypertrophy and dilation, and low normal RV function; 277 proteins were significantly dysregulated (log2FC ≥0.6/≤-0.6, FDR≤0.05), predicting downregulation in lipid transport (apolipoproteins), fibrinolytic system, and extracellular matrix structural proteins (talin 1, profilin 1); and upregulation in the respiratory burst. Increasing RV size and decreasing RV function correlated with decreasing structural protein expression. Similarly, miR expression predicted downregulation of extracellular matrix-receptor interactions and upregulation in collagen synthesis. Conclusion: To our knowledge, we show for the first time a noninvasive protein and miR signature reflecting the systemic response to adverse RV myocardial remodeling in TOF/PA/MAPCAs which could be used to follow disease progression.

Development and validation of a chiral UPLC-MS/MS method for quantifying S-Oxiracetam and R-Oxiracetam in human plasma, urine and feces: Application to a phase-I clinical pharmacokinetic study.

A chiral UPLC-MS/MS method was developed and validated to determine oxiracetam enantiomers in human plasma, urine, and feces. The R-Oxiracetam and S-Oxiracetam were quantified using a CHIRALPAK ®AD3 column at 25 â„ƒ, and the resolution was greater than 3.2. The S-Oxiracetam is the eutomer that isresponsible for the treatment of various brain damage. Isocratic elution was conducted at a flow rate of 0.9 mL/min for 6 min using the mixture of methanol and acetonitrile (methanol:acetonitrile, 15:85) containing 0.3‰ formic acid. The methods showed linearity at the range of 0.5-100 µg/mL for each oxiracetam enantiomer. A comprehensive validation process was carried out, covering aspects including linearity, selectivity, carryover, accuracy, precision, interferences, matrix effect, recovery, dilution integrity and stability in matrix and solution. The validated methods were successfully applied to quantifying R-Oxiracetam and S-Oxiracetam in human plasma, urine, and feces of 12 healthy subjects treated with either a single dose of 2 g S-Oxiracetam injection or 4 g Oxiracetam injection in a phase-I clinical trial. There was no significant difference for plasma pharmacokinetic parameters of S-Oxiracetam between the two regimens (P＞0.05). The S-Oxiracetam and Oxiracetam were primarily eliminated through urine in their original form, with cumulative excretion rates of 92.16% and 85.92%, respectively, within 24 h after administration. Enantiomers interconversion was not observed in the plasma, urine, or feces. The results of this study suggest that replacing 4 g Oxiracetam injection with 2 g S-Oxiracetam injection could offer clinical benefits by lowering the dosage and mitigating potential risks, based on the pharmacokinetic characteristics.

Genome-Wide Identification and Comprehensive Analysis of the FtsH Gene Family in Soybean (Glycine max).

The filamentation temperature-sensitive H (FtsH) gene family is critical in regulating plant chloroplast development and photosynthesis. It plays a vital role in plant growth, development, and stress response. Although FtsH genes have been identified in a wide range of plants, there is no detailed study of the FtsH gene family in soybean (Glycine max). Here, we identified 34 GmFtsH genes, which could be categorized into eight groups, and GmFtsH genes in the same group had similar structures and conserved protein motifs. We also performed intraspecific and interspecific collinearity analysis and found that the GmFtsH family has large-scale gene duplication and is more closely related to Arabidopsis thaliana. Cis-acting elements analysis in the promoter region of the GmFtsH genes revealed that most genes contain developmental and stress response elements. Expression patterns based on transcriptome data and real-time reverse transcription quantitative PCR (qRT-PCR) showed that most of the GmFtsH genes were expressed at the highest levels in leaves. Then, GO enrichment analysis indicated that GmFtsH genes might function as a protein hydrolase. In addition, the GmFtsH13 protein was confirmed to be localized in chloroplasts by a transient expression experiment in tobacco. Taken together, the results of this study lay the foundation for the functional determination of GmFtsH genes and help researchers further understand the regulatory network in soybean leaf development.

Cost-effectiveness analysis of tumor-infiltrating lymphocytes biomarkers guiding chemotherapy de-escalation in early triple-negative breast cancer.

BACKGROUND: To accelerate the clinical translation of tumor-infiltrating lymphocytes (TILs) biomarkers for guiding chemotherapy de-escalation in early-stage triple-negative breast cancer (TNBC), cost-effectiveness evidence is essential but has not been investigated. We intend to evaluate the cost-effectiveness of using TILs to guiding chemotherapy de-escalation in patients with early-stage TNBC from the perspective of the Chinese health service system. METHODS: The hybrid decision-tree-Markov model was designed to compare the cost-effectiveness of cytotoxic chemotherapy guided by whether TILs assay was performed in 50-year-old female patients with early-stage TNBC over a lifetime horizon. In Strategy (1), if TILs testing was performed, patients with TILs values exceeding 30% could be spared from chemotherapy. In Strategy (2), where no TILs testing was performed, all patients were administered chemotherapy following China's clinical practices. Based on the algorithm built by Guyot, the individual patient data were reconstructed from the published Kaplan-Meier curves, and the survival functions were calculated by parametric methods. Cost estimates were valued in Chinese yuan (as per rates in 2022). RESULTS: In 50-year-old female patients with early-stage TNBC, Strategy (1), which employs TILs testing to guide cytotoxic chemotherapy yielded an additional 0.47 quality-adjusted life years (QALYs) and saved 40,976 yuan, with an incremental cost-effectiveness ratio (ICER) of -87,182.98 yuan per QALY gained compared with Strategy (2). This indicates that compared with Strategy (2), Strategy (1) is the dominant scheme. The results were sensitive to utility parameters, discount rates, and treatment costs after relapse. At a willingness-to-pay threshold of 85,700 yuan (based on GDP per capita) per QALY, the probability of TILs being cost-effective was almost 100%. CONCLUSIONS: The application of biomarkers (TILs) to guide decisions for chemotherapy de-escalation is a cost-effective strategy for early-stage TNBC patients and deserves to be widely promoted in clinical practice.

Potential significance of changes in serum levels of IL-17, TNF-α and DKK-1 in the progression of the rheumatoid arthritis.

To detect the value of serum interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) at different disease stages. 141 RA patients were randomly obtained and diagnosed in a large tertiary first-class hospital in Jiangxi Province from November 2021 to January 2022. RA was divided into 38 low activity and remission phase (low remission patients), 72 moderate activity patients, 41 high activity patients, according to the disease activity score 28 (DAS28) of RA and 70 healthy controls. IL-17 and TNF-α in serum detected by flow cytometry; DKK-1by ELISA; rheumatoid factor (RF) and C-reactive protein (CRP) by rate scattering turbidimetry; erythrocyte sedimentation rate (ESR) by Widmanstat method; anti-cyclic citrullinated polypeptide antibody (Anti-CCP) by chemiluminescence. The changes among the groups were statistically analysed and evaluated their diagnostic value. ①Anti-CCP, CRP, and ESR levels in the moderate-to-high activity group were higher than controls, while IL-17, TNF-α, and DKK-1levels higher than low remission group, moderate activity group and controls (p < 0.05). ②IL-17, TNF-α and DKK-1 were positively correlated with RA disease activity, with the correlations of IL-17, TNF-α and DKK-1 all over 0.5 (p < 0.05). ③The ROC curve showed that among all indices the AUC of DKK-1 was the largest, 0. 922, and has the highest sensitivity and negative predictive value for RA, 0.965 and 0.953, respectively. The specificity and positive predictive value of TNF-α is highest, 0.918 and 0.921, respectively, combined them had the highest predictive value in moderate-to-high activity RA, with AUC of 0.968, and had the highest sensitivity of 0.965. The IL-17, TNF-α and DKK-1 levels were elevated in RA and positively correlated with disease activity, involved in the Wnt signalling pathway of inflammatory and joint destructive effects, combining them to monitor the RA disease process and biologically treat the cytokines in the pathogenesis of RA were valuable.

A new strategy for browning regulation: Flos Sophorae Immaturus extract and thermal treatment modulates nitric oxide and reactive oxygen species network in fresh-cut potatoes.

Browning discoloration is a critical issue that negatively affects the quality of fresh-cut products and their industrial growth. Although many individual anti-browning technologies have been adopted, very few reports on the combination use of natural product extracts and physical methods exist. This study investigated the use of Flos Sophorae Immaturus extract in conjunction with thermal treatment and discovered that the combination effectively retarded browning in fresh-cut potatoes. Accordingly, the activities of polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase, as well as phenol accumulation, were effectively regulated. Meanwhile, this combination treatment also allowed for the modulation of nitric oxide synthase, superoxide dismutase, and catalase activities, while also regulating the concentrations of nitric oxide, superoxide anion, and hydrogen peroxide. Furthermore, the duplex treatment also regulated the antioxidant capacity and malondialdehyde concentrations. In addition, 39 phytoactive compounds, including protocatechuic acid, quercetin, (-)-alpha-pinene, and matrine, were identified in the extract, which may function as the anti-browning composition. These findings suggest that the combination technology modulated the dynamic equilibrium of production and clearance of nitric oxide and reactive oxygen species, thereby reducing browning deterioration. This is, to our knowledge, the first report of the combined application of Flos Sophorae Immaturus and thermal treatment, which may offer a novel option for fresh-cut preservation. PRACTICAL APPLICATION: The feasibility of integrating a novel highly efficient, safe, environmentally friendly, and easy-to-operate anti-browning alternative, with the ability to integrate into the existing processing line was investigated. The color of sliced potato chips was significantly improved (73.4%) by dipping them in a 0.01% Flos Sophorae Immaturus solution for 5 min and then in 55°C water for 2 min. In this regard, superior browning alleviation may depend on the regulation of the browning reaction and the NO-ROS network. This method has a promising future for making fresh-cut products more appealing to consumers and may provide guidance for fresh-cut producers and related industries.

Advances in Extraction, Purification, and Analysis Techniques of the Main Components of Kudzu Root: A Comprehensive Review.

Kudzu root (Pueraria lobate (Willd.) Ohwi, KR) is an edible plant with rich nutritional and medicinal values. Over the past few decades, an ample variety of biological effects of Pueraria isoflavone have been evaluated. Evidence has shown that Pueraria isoflavone can play an active role in antioxidant, anti-inflammatory, anti-cancer, neuroprotection, and cardiovascular protection. Over 50 isoflavones in kudzu root have been identified, including puerarin, daidzein, daidzin, 3'-hydroxy puerarin, and genistein, each with unambiguous structures. However, the application of these isoflavones in the development of functional food and health food still depends on the extraction, purification and identification technology of Pueraria isoflavone. In recent years, many green and novel extraction, purification, and identification techniques have been developed for the preparation of Pueraria isoflavone. This review provides an updated overview of these techniques, specifically for isoflavones in KR since 2018, and also discusses and compares the advantages and disadvantages of these techniques in depth. The intention is to provide a research basis for the green and efficient extraction, purification, and identification of Pueraria isoflavone and offers investigators a valuable reference for future studies on the KR.

Poly(ether ether ketone) Conferred Polyolefin Separators with High Dimensional Thermal Stability for Lithium-Ion Batteries.

The traditional polyolefin separators used in lithium-ion batteries (LIBs) are plagued by limitations such as poor wetting of electrolytes and insufficient thermal stability, hindering the progress of LIBs. To overcome these limitations, we have developed a modified phase inversion technique to efficiently and durably coat polyolefin separators with poly(ether ether ketone) (PEEK). The resulting PEEK-coated polyolefin separators exhibit mechanical properties similar to those of unmodified polyolefin separators, with comparable tensile strength and modulus. Furthermore, the PEEK coating provides outstanding thermal stability, as the modified separators maintain their stability even at temperatures up to 200 °C, which is among the best results reported for polyolefin-based separators. In addition, the PEEK coating enhances ionic conductivity by more than 100% compared to polyolefin counterparts, leading to significant improvement in the electrochemical performance of prototype half cells. The modified phase inversion technique presented here offers a practical solution for coating polyolefin separators with functional polymers, paving the way for next-generation separator materials.