Enhancing Pseudomonas syringae pv. Actinidiae sensitivity in kiwifruit by repressing the NBS-LRR genes through miRNA-215-3p and miRNA-29-3p identification.

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit's response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit's sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit's defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.

Clinical research progress of telomerase targeted cancer immunotherapy: a literature review.

Background and Objective: Telomerase is activated or overexpressed in 85-90% of tumors, which maintains the length of telomere and has become an important anti-cancer target. Increasing clinical and preclinical data suggest that telomerase-targeted cancer immunotherapy could achieve effective killing of tumor cells in vivo. This article reviews the research progress of telomerase targeted cancer immunotherapy in clinical and pre-clinical trials, aiming to provide a reference for further clinical research and treatment of cancers. Methods: We investigated the research progress of telomerase immunotherapy in the last 20 years from four electronic databases. Key Content and Findings: Telomerase-targeted immunotherapies have been developed with the arising of a new era in immuno-oncology, including peptide vaccines, DNA vaccines, dendritic cells (DCs), adoptive cell transfer (ACT) therapies, antibodies, etc. Some of them have been approved for undergoing clinical trials by the Food and Drug Administration (FDA) for the treatment of various cancers, such as pancreatic cancer, non-small cell lung cancer, melanoma, leukaemia. Of all the treatment modalities, vaccines are the primary treatment methods, some of which have been even entered into phase III clinical trials. The main clinical application direction of telomerase vaccine is the combination with other drugs and treatment modalities, including combination with other vaccines targeting human telomerase reverse transcriptase (hTERT), traditional chemotherapy drugs and immunosuppressors. We also summarized the recent findings of immunotherapy targeting hTERT, focusing on various vaccines and the current status of associated clinical trials. We further discussed the advantages, disadvantages and potential developmental directions of various telomerase-targeted immunotherapies. Conclusions: Telomerase-targeted cancer immunotherapy has promising prospects in improving patient survival expectancy. This review may provide data support and design ideas for all researchers and pharmaceutical enterprises in this field.

Correction: A robust and porous titanium metal-organic framework for gas adsorption, CO2 capture and conversion.

Correction for 'A robust and porous titanium metal-organic framework for gas adsorption, CO2 capture and conversion' by Xuze Pan, et al., Dalton Trans., 2023, 52, 3896-3906, https://doi.org/10.1039/D2DT03158B.

PD-L1 siRNA hitched polyethyleneimine-elastase constituting nanovesicle induces tumor immunogenicity and PD-L1 silencing for synergistic antitumor immunotherapy.

BACKGROUND: PD-1/PD-L1 blockade has become a powerful method to treat malignant tumors. However, a large proportion of patients still do not benefit from this treatment, due to low tumor immunogenicity and low tumor penetration of the agents. Recently, neutrophil elastase has been shown to induce robust tumor immunogenicity, while the insufficient enzyme activity at the tumor site restricted its anti-tumor application. Here, we designed polyethyleneimine-modified neutrophil elastase (PEI-elastase) loaded with PD-L1small interfering RNA (PD-L1 siRNA) for improving enzymatic activity and delivering siRNA to tumor, which was expected to solve the above-mentioned problems. RESULTS: We first demonstrated that PEI-elastase possessed high enzymatic activity, which was also identified as an excellent gene-delivery material. Then, we synthesized anti-tumor lipopolymer (P-E/S Lip) by encapsulating PEI-elastase and PD-L1siRNA with pH-responsive anionic liposomes. The P-E/S Lip could be rapidly cleaved in tumor acidic environment, leading to exposure of the PEI-elastase/PD-L1 siRNA. Consequently, PEI-elastase induced powerful tumor immunogenicity upon direct tumor killing with minimal toxicity to normal cells. In parallel, PEI-elastase delivered PD-L1siRNA into the tumor and reduced PD-L1 expression. Orthotopic tumor administration of P-E/S Lip not only attenuated primary tumor growth, but also produced systemic anti-tumor immune response to inhibit growth of distant tumors and metastasis. Moreover, intravenous administration of P-E/S Lip into mice bearing subcutaneous tumors leaded to an effective inhibition of established B16-F10 tumor and 4T1 tumor, with histological analyses indicating an absence of detectable toxicity. CONCLUSIONS: In our study, a protease-based nanoplatform was used to cooperatively provoke robust tumor immunogenicity and down-regulate PD-L1 expression, which exhibited great potential as a combination therapy for precisely treating solid tumors.

Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy.

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

Discharge teaching quality positively predicts quality of life in colorectal cancer patients with temporary enterostomy: The mediating role of readiness for hospital discharge and stoma self-efficacy.

OBJECTIVES: This study aimed to examine the mediating role of readiness for hospital discharge (RHD) and stoma self-efficacy (SSE) in the relationship between quality of discharge teaching (QDT) and health-related quality of life (HRQOL) in colorectal cancer patients with temporary enterostomy, and the gender difference of mediating effect. BACKGROUND: It is not clear how RHD, QDT, SSE and HRQOL interact in colorectal cancer patients with temporary enterostomy. METHODS: This was a prospective follow-up survey. 221 colorectal cancer patients with temporary enterostomy were conveniently recruited from a general hospital in Southeast China. The Quality of Discharge Teaching Scale, Readiness for Hospital Discharge Scale, Stoma Self-Efficacy Scale, and Stoma Quality of Life Scale were used to collect data. Pearson's correlation and structural equation models were used to analyze the data. SPSS 26.0 and Amos 28.0 software were used for analysis the collected data. RESULTS: Regarding the relationship of QDT and HRQOL, only QDT-T had a direct effect among colorectal cancer patients with stomas (b = 0.233, P<0.001, percentile 95% CI = [0.145, 0.314]). However, both QDT-T and QDT-R can predict HRQOL indirectly through three paths: (1) the mediating role of SSE (b = 0.050, P = 0.009, percentile 95% CI = [0.013, 0.098]; b = 0.077, P = 0.008, percentile 95% CI = [0.021, 0.164]), (2) the mediating role of RHD (b = 0.044, P = 0.004, percentile 95% CI = [0.014, 0.085]; b = 0.044, P = 0.005, percentile 95% CI = [0.010, 0.102]), and (3) the chain mediating role of SSE and RHD (b = 0.030, P = 0.003, percentile 95% CI = [0.011, 0.059]; b = 0.047, P = 0.003, percentile 95% CI = [0.015, 0.103]). The similar chain mediating effect in male stoma patients was also found (b = 0.041, P = 0.002, percentile 95% CI = [0.016, 0.080]; b = 0.046, P = 0.004, percentile 95% CI = [0.011, 0.114]). CONCLUSIONS: Stoma self-efficacy and readiness for hospital discharge played important intermediary roles in the relationship between quality of discharge teaching and health-related quality of life in colorectal cancer patients with stomas. Health care providers can design SSE-enhancing and RHD-enhancing discharge planning for colorectal cancer patients with temporary enterostomies.

Iron deposition participates in LPS-induced cognitive impairment by promoting neuroinflammation and ferroptosis in mice.

Neuroinflammation is a common pathological feature and onset in multiple cognitive disorders, including postoperative cognitive dysfunction (POCD). Iron deposition was proved to participate in this process. But how iron mediates inflammation-induced cognitive deficits remains unknown. This study aimed to investigate the mechanism of iron through the neuroprotective effect of the iron chelator deferoxamine (DFO) in a mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Adult C57BL/6 mice were pretreated with 0.5 µg of DFO three days before intracerebroventricular microinjection of 2 µg of LPS. The mice showed memory deficits by showing decreased percentage of distance and the time within the platform-site quadrant, fewer platform-site crossings, and shortened swimming distance around the platform in the Morris water maze test, which were significantly mitigated by DFO pretreatment. Mechanistically, DFO prevented LPS-induced iron accumulation and modulated the imbalance of proteins expression related to iron metabolism, including elevated transferrin (TF) levels and reduced ferritin (Fth) caused by LPS. DFO attenuated the LPS-induced lipid peroxidation and oxidative stress, which is evidenced by the decrease of malondialdehyde (MDA) and lipid peroxidation (LPO) levels and the increase of superoxide dismutase (SOD) activity and glutathione (GSH) concentration. Moreover, DFO ameliorated ferroptosis-like mitochondrial damages in the hippocampus and also alleviated the expression of ferroptosis-related proteins in the hippocampus. Additionally, DFO attenuated microglial activation, alleviated LPS-induced inflammation, and reduced elevated levels of IL-6 and TNF-α in the hippocampus. Taken together, our findings suggested that DFO exerts neuroprotective effects by alleviating excessive iron participation in lipid peroxidation, reducing the occurrence of ferroptosis, inhibiting the vicious cycle between oxidative stress and inflammation, and ultimately ameliorating LPS-induced cognitive dysfunction, providing novel insights into the immunopathogenesis of inflammation-related cognitive dysfunction and future potential prevention options targeting iron.

Prenatal diagnosis of a skeletal disorder characterized by rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene: Case report and literature review.

BACKGROUND: The protein kinase domain containing cytoplasmic (PKDCC) gene (OMIM#618821) is associated with bone development. Biallelic variants in the PKDCC gene can cause rhizomelic limb shortening with dysmorphic features. CASE REPORT: A fetus was found to be rhizomelic limb shortening at 16 weeks of gestation and amniocentesis was performed at 19 weeks of gestation. Genomic DNA extracted from the amniotic fluid was subjected to chromosomal microarray analysis (CMA), and Trio-total whole-exome sequencing (Trio-WES). Sanger sequencing was used to verify the candidate pathogenic variants. CMA was normal, while Trio-WES identified two compound heterozygous variants in the PKDCC gene, namely c.417_c.423delCGGCGCG insTCATGGGCTCAGTACAC(p.G140fs*35) and c.345G>A (p.W115*,379). Then the fetus was aborted and the development of its bone cells were compared with that of a normal fetus of similar gestational age by histopathological examination. Clinical findings of the fetus were shortening humerus and femur, synophrys, much hair on the side face, simian line on the right palm, etc. Histopathological examination showed that the affected fetus had increased proliferative chondrocytes, widened proliferative bands, and delayed bone mineralization. CONCLUSIONS: We reported a prenatal case of rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene, which emphasized the important role of Trio-WES for diagnosis of skeletal dysplasia in fetuses.

Implicit theories of health predict HPV vaccination intention among young adult Chinese women: The mediating effect of consideration of future consequences and future self-continuity.

This study investigated the predicting effect of implicit theories of health on HPV vaccination intention among young adult Chinese women and its underlying mechanisms. Four-hundred and eighty-three young Chinese women adults (18-26 years old) participated this study by completing measures on implicit theories of health, consideration of future consequences, future self-continuity, and reported their HPV vaccination intention. The results demonstrated that age, whether they knew someone being diagnosed with cancer, implicit (incremental) theories of health, consideration of future consequences (CFC-Future), and future self-continuity significantly predicted young adult Chinese women's HPV vaccination intention. The predicting effect of implicit theories of health was mediated by consideration of future consequences and future self-continuity. Implications of the current research for promoting HPV vaccination among young adult women and directions for future research are discussed.

Relationship between preoperative high triglyceride-glucose index and myocardial injury following non-cardiac surgery in advanced-age patients: a retrospective cohort study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and insidious postoperative complication. This study aimed to evaluate the relationship between the triglyceride-glucose index (TyG) and MINS in advanced-age patients. METHODS: We performed a single-center retrospective study including patients ≥ 65 years of age who underwent non-cardiac surgery. The relationship between TyG and MINS was investigated using univariate and multivariate logistic regression analyses. Multivariate logistic regression analysis involved three models: Model I adjusted for preoperative factors, Model II adjusted for surgery-related factors, and Model III adjusted for both preoperative and surgery-related factors. Propensity score matching (PSM) was used to reduce the confounding effects of covariates. Subgroup analyses were then performed to evaluate the relationship between TyG and MINS in various subsamples. RESULTS: A total of 7789 patients were studied, among whom 481 (6.2%) developed MINS. A cut-off value of TyG of 8.57 was determined using a receiver operating characteristic (ROC) curve to be associated with the best predictive performance. Participants with TyG ≥ 8.57 were at a higher risk of developing MINS than those with TyG < 8.57 [n = 273 (7.6%) vs. n = 208 (4.9%), respectively; p < 0.001]. The univariate analysis showed that TyG ≥ 8.57 was significantly associated with MINS in elderly patients [odds ratio (OR): 1.58; 95% confidence interval (95%CI): 1.32-1.91; p < 0.001)]. In multivariate logistic regression, adjustments were made for risk factors including age, sex, body mass index (BMI), hypertension, coronary heart disease, and duration of surgery, etc. The adjusted ORs for TyG ≥ 8.57 were 1.46 (95%CI: 1.17-1.82), p = 0.001; 1.46 (95%CI: 1.19-1.77), p < 0.001; and 1.43 (95%CI: 1.13-1.81), p = 0.003, in the three multivariate models, respectively. The relationship remained after PSM (adjusted OR: 1.35, 95% CI: 1.03-1.78, p = 0.029). Furthermore, the relationship between TyG and MINS remained in a number of subgroups in the sensitivity analyses, but not in participants with peripheral vascular stenosis. CONCLUSIONS: A preoperative high TyG (≥ 8.57) is associated with a higher risk of MINS in advanced-age patients undergoing non-cardiac surgery.

Aqueous extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim. induces liver injury in mice via pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms. MATERIALS AND METHODS: Dried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1ß was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum. RESULTS: E. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1ß levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased. CONCLUSIONS: Our results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis.

Clinical performance of metagenomic next-generation sequencing for diagnosis of invasive fungal disease after hematopoietic cell transplant.

Background: Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. Methods: We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Results: Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. Conclusion: mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.

Alcalase-hydrolyzed insoluble soybean meal hydrolysate aggregates: Structure, bioactivity, function properties, and influences on the stability of oil-in-water emulsions.

We studied the influences of hydrolysis time on the structure, functional properties, and emulsion stability of insoluble soybean meal hydrolysate aggregates (ISMHAs). We assume that the ISMHAs produced by soybean meal can be used as emulsifiers to prepare stable emulsions. The molecular weights of these ISMHAs were below 53 kDa. After hydrolysis, a decrease in α-helices and an increase in random coils indicated that the soybean meal proteins were unfolding. Moreover, the fluorescence intensity, UV absorption, and surface hydrophobicity of ISMHAs increased. These results would contribute to their antioxidant activity and functional properties. Additionally, the 90-min ISMHA sample exhibited the highest ABTS+• scavenging activity (80.02 ± 4.55 %), foaming stability (52.92 ± 8.06 %), and emulsifying properties (emulsifying activity index of 97.09 m2/g; emulsifying stability index of 371.47 min). The 90-min ISMHA emulsion exhibited the smallest particle size and excellent storage stability. Soybean meal peptide by-product emulsifier has potential for sustainable application.

Riemerella anatipestifer UvrC is required for iron utilization, biofilm formation and virulence.

UvrC is a subunit of excinuclease ABC, which mediates nucleotide excision repair (NER) in bacteria. Our previous studies showed that transposon Tn4531 insertion in the UvrC encoding gene Riean_1413 results in reduced biofilm formation by Riemerella anatipestifer strain CH3 and attenuates virulence of strain YZb1. In this study, whether R. anatipestifer UvrC has some biological functions other than NER was investigated. Firstly, the uvrC of R. anatipestifer strain Yb2 was in-frame deleted by homologous recombination, generating deletion mutant ΔuvrC, and its complemented strain cΔuvrC was constructed based on Escherichia coli - R. anatipestifer shuttle plasmid pRES. Compared to the wild-type (WT) R. anatipestifer strain Yb2, uvrC deleted mutant ΔuvrC significantly reduced biofilm formation, tolerance to H2O2- and HOCl-induced oxidative stress, iron utilization, and adhesion to and invasion of duck embryonic hepatocytes, but not its growth curve and proteolytic activity. In addition, animal experiments showed that the LD50 value of ΔuvrC in ducklings was about 13-fold higher than that of the WT, and the bacterial loads in ΔuvrC infected ducklings were significantly lower than those in Yb2-infected ducklings, indicating uvrC deletion in R. anatipestifer attenuated virulence. Taken together, the results of this study indicate that R. anatipestifer UvrC is required for iron utilization, biofilm formation, oxidative stress tolerance and virulence of strain Yb2, demonstrating multiple functions of UvrC.RESEARCH HIGHLIGHTSDeletion of uvrC in R. anatipestfer Yb2 significantly reduced its biofilm formation.uvrC deletion led to reduced tolerance to H2O2- and HOCl-induced oxidative stress.The iron utilization of uvrC deleted mutant was significantly reduced.The uvrC deletion in R. anatipestifer Yb2 attenuated its virulence.

Effects of different aging methods on the ability of biochar to adsorb heavy metal cadmium and its physical and chemical properties.

The aging process can affect the physical and chemical properties as well as adsorption capacity of biochar. This study focuses on the heavy metal cadmium (Cd) as the research object, and artificially ages biochar prepared from rice straw and corn straw through accelerated freeze-thaw cycles, alternating dry wet cycles, and ultraviolet light treatment, in order to evaluate the effects of different aging conditions on the physical and chemical properties of the two different types of biochar and on their adsorption capacities for Cd. After aging, the pH of rice and corn biochar decreased to varying degrees, respectively. The surface structure was ruptured, the average pore diameter was decreased, and the specific surface area was increased by 27.3%, 21.9%, and 9.8% (rice) and 95.4%, 27.7%, and 13.4% (corn). Ultraviolet light aging has the most significant impact on the elemental content of biochar, and the C content was decreased by 12.4% (rice) and 9.3% (corn). The O content was increased by 11.2% (rice) and 44.1% (corn), and the numbers of O/C, H/C, (O + N)/C, and oxygen-containing functional groups were increased. These results demonstrate that the aging process reduces the degree of aromatization of biochar, while enhancing its polarity and Cd adsorption capacity. Rice straw biochar (RSB) has a greater ability to adsorb Cd than corn straw biochar (CSB). In addition, ultraviolet light aging is particularly effective in increasing heavy metal adsorption.

Diagnosing postoperative lymph node metastasis in thyroid cancer with multimodal radiomics and clinical features.

Purpose: This study aims to evaluate the diagnostic value of texture analysis for lymph node metastasis after thyroid cancer surgery. Methods: We retrospectively analyzed patients who underwent positron emission tomography/computed tomography (PET/CT) examination before 131I treatment at Shanghai Tenth People's Hospital between 2017 and 2020. Clinical follow-up results were used as the criterion for determining the presence of lymph node metastasis. The study included 119 patients, who were then randomly divided into training and test groups in a 7:3 ratio. Regions of interest were identified, and radiomics features were extracted using LIFEx 7.3.0. Mann-Whitney U test and LASSO regression were employed to screen radiomics parameters for modeling. Subsequently, a nomogram model was built by combining radscore and clinical features. SPSS 26.0 software was utilized for statistical analysis, and p < 0.05 was considered statistically significant. Results: Follow-up confirmed 54 patients with thyroid cancer lymph node metastasis and 65 patients in the non-metastasis group. A total of 119 lymph nodes were delineated. For each lesion, 164 CT texture features and 164 PET texture features were extracted, and 107 significant parameters were identified, including 16 CT texture parameters and 91 PET texture parameters. After screening, 3 CT parameters, 4 PET parameters and 12 PET/CT parameters were selected to establish three radiomic models. The AUC values were as follows: AUC (CT) = 0.730, AUC (PET) = 0.759 and AUC (PET/CT) = 0.864. We then combined clinical features and radscore to construct a nomogram, resulting in a C-index of 0.915 in the training group. In the test group, the C-index was confirmed to be 0.868. Conclusions: Radiomics may enhance the diagnostic efficiency of lymph node metastases after thyroid cancer surgery and could potentially assist clinicians in future diagnoses. The developed nomogram, which combines radiomics and clinical features, offers relatively high accuracy in helping clinicians assess the risk of metastasis in thyroid patients after surgery.

Comparison of calcium magnesium ferrite nanoparticles for boosting biohydrogen production.

Dark fermentation (DF) is an eco-friendly process that simultaneously achieves organic matter degradation and obtains hydrogen (H2). Nonetheless, low H2 yield mainly caused by poor activity of key microbes, is still a problem that requires being resolved. In this work, MgFe2O4 and Ca0.5Mg0.5Fe2O4 nanoparticles (NPs) were synthetized and served as additives to boost H2 form from DF. H2 productivity gradually increased with the rise of NPs, and declined when NPs exceeded their optimal dosages. The highest H2 yield was 183.6 ± 3.2 mL/g glucose at 100 mg/L of MgFe2O4 NPs, being 35.2 % higher than that of the control yield (135.8 ± 3.1 mL/g glucose). However, the highest H2 yield of 171.9 ± 2.5 mL/g glucose occurred at 400 mg/L of Ca0.5Mg0.5Fe2O4 NPs, increasing by 26.6 % over the control. Interestingly, the two NPs favored the butyric acid pathway for H2 synthesis. This provides guidance for multi-element oxide NPs used in DF.

Identify novel inflammation-related prognostic signature in pancreatic cancer patients.

Pancreatic cancer (PC) is a malignant tumor of the digestive system with a poor prognosis. PC patients with pancreatitis have a worse prognosis. But nobody reported the relationship between inflammation and prognosis in PC. Based on this, we are going to explore inflammation-related prognostic signature to predict patients' survival and potential therapeutic target. We screened gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to identify differentially expressed genes (DEGs) between tumor and normal tissues with P value < .05. Univariate and multivariate Cox regression analysis was applied to identify possible prognostic inflammation genes and establish an inflammation-related risk score system, which was validated by Kaplan-Meier and Receiver operating characteristic (ROC) curves. Finally, we used the TISIDB database to predict targeted drugs for up-regulated gene hepatocyte growth factor receptor (MET) and used AUTODOCK software for molecular docking. We built a prognostic model consisted of 3 inflammation-related genes (tumor necrosis factor receptor associated factor 1/TFAR1, tyrosine kinase 2/TYK2, MET). According to the median value of those genes' risk score, PC patients were ranked into high- (88) and low-risk (89) groups. Then, the results of the Kaplan-Meier curves and the area under the curve (AUC) of the ROC curves showed this model had a good predictive power (P < .001, AUC = 0.806). The result of human protein atlas (HPA) database showed the expression of TRAF1 and TYK2 were low in pancreatic cancer, the expression of MET was high. TISIDB database founded brigatinib could target to MET. And AUTODOCK showed brigatinib had a nice docking with MET. Taken together, our study suggested that inflammation-associated prognostic signature might be used as novel biomarkers for predicting prognosis in PC patients and potential therapeutic target of the disease.

Protein Kinase A Is a Master Regulator of Physiological and Pathological Cardiac Hypertrophy.

BACKGROUND: The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors. If and how PKA plays a role in physiological cardiac hypertrophy (PhCH) and pathological CH (PaCH) are not clear. METHODS: Transgenic mouse models expressing the PKA inhibition domain (PKAi) of PKA inhibition peptide alpha (PKIalpha)-green fluorescence protein (GFP) fusion protein (PKAi-GFP) in a cardiac-specific and inducible manner (cPKAi) were used to determine the roles of PKA in physiological CH during postnatal growth or induced by swimming, and in PaCH induced by transaortic constriction (TAC) or augmented Ca2+ influx. Kinase profiling was used to determine cPKAi specificity. Echocardiography was used to determine cardiac morphology and function. Western blotting and immunostaining were used to measure protein abundance and phosphorylation. Protein synthesis was assessed by puromycin incorporation and protein degradation by measuring protein ubiquitination and proteasome activity. Neonatal rat cardiomyocytes (NRCMs) infected with AdGFP (GFP adenovirus) or AdPKAi-GFP (PKAi-GFP adenovirus) were used to determine the effects and mechanisms of cPKAi on myocyte hypertrophy. rAAV9.PKAi-GFP was used to treat TAC mice. RESULTS: (1) cPKAi delayed postnatal cardiac growth and blunted exercise-induced PhCH; (2) PKA was activated in hearts after TAC due to activated sympathoadrenergic system, the loss of endogenous PKIα (PKA inhibition peptide α), and the stimulation by noncanonical PKA activators; (3) cPKAi ameliorated PaCH induced by TAC and increased Ca2+ influxes and blunted neonatal rat cardiomyocyte hypertrophy by isoproterenol and phenylephrine; (4) cPKAi prevented TAC-induced protein synthesis by inhibiting mTOR (mammalian target of rapamycin) signaling through reducing Akt (protein kinase B) activity, but enhancing inhibitory GSK-3α (glycogen synthase kinase-3α) and GSK-3ß signals; (5) cPKAi reduced protein degradation by the ubiquitin-proteasome system via decreasing RPN6 phosphorylation; (6) cPKAi increased the expression of antihypertrophic atrial natriuretic peptide (ANP); (7) cPKAi ameliorated established PaCH and improved animal survival. CONCLUSIONS: Cardiomyocyte PKA is a master regulator of PhCH and PaCH through regulating protein synthesis and degradation. cPKAi can be a novel approach to treat PaCH.

Quantum Dot-Based Immunoassays: Unraveling Sensitivity Discrepancies and Charting Future Frontiers.

The 2023 Nobel Prize in Chemistry honors the groundbreaking contributions of Alexei Ekimov, Louis Brus, and Moungi Bawendi to the field of quantum dots (QDs). In this spirit, we developed a direct competitive QD fluorescence immunoassay (dc-QD-FLISA) to detect aristolochic acid type I (AAI), a potent carcinogen found in herbal remedies. Unexpectedly, the dc-QD-FLISA exhibited lower sensitivity than that of an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA), contrary to our initial expectations. This discrepancy in the sensitivity prompted a comprehensive analysis of the entire experimental process. We propose that steric hindrance between QDs and antigen-binding sites on antibodies may significantly diminish the binding efficiency, reducing sensitivity within the dc-QD-FLISA method. Furthermore, issues such as buffer conditions, antibody handling, and separation methods are also contributing factors. We recommend site-directed QD modification and stringent consideration of the experimental conditions. This study not only provides insights into QD-based immunoassays but also highlights the need for future advancements in immunoassay technology in terms of augmenting sensitivity and specificity, potentially revolutionizing disease diagnosis, biomarker discovery, and biomedical research.