4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2/HO-1 signalling pathway.

Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI-OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH-DA. Real-time PCR quantified inflammatory cytokines TNF-α, IL-6 and IL-1ß. Network Pharmacology and RNA sequencing (RNA-seq) analysis of the potential mechanism of 4-OI resistance to cisplatin-induced ferroptosis. The expressions of ferroptosis-related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO-1, GCLC and NQO1) were tested by real-time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin-induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4-OI exhibited anti-inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin-induced cell loss. In the present study, we show that 4-OI inhibits cisplatin-induced ferroptosis possibly through activation of the NRF2/HO-1 signalling pathway, thereby exerting a protective effect against cisplatin-induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin-induced hearing loss.

Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib.

BACKGROUND: Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There is an urgent need to identify specific biomarkers for cancer subtyping and early detection to enhance both morbidity and mortality outcomes. The addition of the EGFR tyrosine kinase inhibitor (TKI), erlotinib, to gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer slightly improved outcomes. However, restricted clinical benefits may be linked to the absence of well-characterized criteria for stratification and dependable biomarkers for the prediction of treatment effectiveness. METHODS AND RESULTS: We examined the levels of various cancer hallmarks and identified glycolysis as the primary risk factor for overall survival in PC. Subsequently, we developed a glycolysis-related score (GRS) model to accurately distinguish PC patients with high GRS. Through in silico screening of 4398 compounds, we discovered that erlotinib had the strongest therapeutic benefits for high-GRS PC patients. Furthermore, we identified ARNTL2 as a novel prognostic biomarker and a predictive factor for erlotinib treatment responsiveness in patients with PC. Inhibition of ARNTL2 expression reduced the therapeutic efficacy, whereas increased expression of ARNTL2 improved PC cell sensitivity to erlotinib. Validation in vivo using patient-derived xenografts (PDX-PC) with varying ARNTL2 expression levels demonstrated that erlotinib monotherapy effectively halted tumor progression in PDX-PC models with high ARNTL2 expression. In contrast, PDX-PC models lacking ARNTL2 did not respond favorably to erlotinib treatment. Mechanistically, we demonstrated that the ARNTL2/E2F1 axis-mediated cellular glycolysis sensitizes PC cells to erlotinib treatment by activating the PI3K/AKT signaling pathway. CONCLUSIONS: Our investigations have identified ARNTL2 as a novel prognostic biomarker and predictive indicator of sensitivity. These results will help to identify erlotinib-responsive cases of PC and improve treatment outcomes. These findings contribute to the advancement of precision oncology, enabling more accurate and targeted therapeutic interventions.

The radiomics nomogram predicts the prognosis of pancreatic cancer patients with hepatic metastasis after chemoimmunotherapy.

OBJECTIVE: To construct a prognostic model based on MR features and clinical data to evaluate the progression free survival (PFS), overall survival (OS) and objective response rate (ORR) of pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy. METHODS: 105 pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy were assigned to the training set (n = 52), validation set (n = 22), and testing set (n = 31). Multi-lesion volume of interest were delineated, multi-sequence radiomics features were extracted, and the radiomics models for predicting PFS, OS and ORR were constructed, respectively. Clinical variables were extracted, and the clinical models for predicting PFS, OS and ORR were constructed, respectively. The nomogram was jointly constructed by radiomics model and clinical model. RESULT: The ORR exhibits no significant correlation with either PFS or OS. The area under the curve (AUC) of nomogram for predicting 6-month PFS reached 0.847 (0.737-0.957), 0.786 (0.566-1.000) and 0.864 (0.735-0.994) in the training set, validation set and testing set, respectively. The AUC of nomogram for predicting 1-year OS reached 0.770 (0.635-0.906), 0.743 (0.479-1.000) and 0.818 (0.630-1.000), respectively. The AUC of nomogram for predicting ORR reached 0.914 (0.828-1.00), 0.938 (0.840-1.00) and 0.846 (0.689-1.00), respectively. CONCLUSION: The prognostic models based on MR imaging features and clinical data are effective in predicting the PFS, OS and ORR of chemoimmunotherapy in pancreatic cancer patients with hepatic metastasis, and can be used to evaluate the prognosis of patients.

Highly Flexible and Superelastic Graphene Nanofibrous Aerogels for Intelligent Sign Language.

Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels. The mechanical robustness is demonstrated to be derived from the trans-scale porous structure, which is composed of hyperbolic micropores and porous nanofibers to enable the large elastic deformation capability. It is further revealed that flexible and superelastic GNFAs exhibit high sensitivity and ultrastability as an electrical sensors to detect tension and flexion deformation. As proof, The GNFA sensor is implemented onto a human finger and achieves the intelligent recognition of sign language with high accuracy by multi-layer artificial neural network. This study proposes a highly flexible and elastic graphene aerogel for wearable human-machine interfaces in sensor technology.

Use of extreme gradient boosting, light gradient boosting machine, and deep neural networks to evaluate the activity stage of extraocular muscles in thyroid-associated ophthalmopathy.

PURPOSE: To develop a machine learning model to evaluate the activity stage of extraocular muscles in thyroid-associated ophthalmopathy (TAO). METHODS: This study retrospectively analysed data from patients with TAO who underwent contrast-enhanced magnetic resonance imaging (MRI) from 2015 to 2022. Three independent machine learning models, namely, extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and deep neural networks (DNNs), were constructed using common clinical features. The performance of these models was compared using evaluation metrics such as the area under the receiver operating curve (AUC), accuracy, precision, recall, and F1 score. The importance of features was explained using Shapley additive explanations (SHAP). RESULTS: A total of 2561 eyes of 1479 TAO patients were included in this study. The original dataset was randomly divided into a training set (80%, n = 2048) and a test set (20%, n = 513). In the performance evaluation of the test set, the LightGBM model had the best diagnostic performance (AUC 0.9260). According to the SHAP results, features such as conjunctival congestion, swollen caruncles, oedema of the upper eyelid, course of TAO, and intraocular pressure had the most significant impact on the LightGBM model. CONCLUSION: This study used contrast-enhanced MRI as an objective evaluation criterion and constructed a LightGBM model based on readily accessible clinical data. The model had good classification performance, making it a promising artificial intelligence (AI)-assisted tool to help community hospitals evaluate the inflammatory activity of extraocular muscles in TAO patients in a timely manner.

Long-term trends of lung cancer incidence and survival in southeastern China, 2011-2020: a population-based study.

BACKGROUND: Lung cancer is the primary cause of cancer-related deaths in China. This study analysed the incidence and survival trends of lung cancer from 2011 to 2020 in Fujian Province, southeast of China, and provided basis for formulating prevention and treatment strategies. METHODS: The population-based cancer data was used to analyse the incidence of lung cancer between 2011 and 2020, which were stratified by sex, age and histology. The change of incidence trend was analysed using Joinpoint regression. The relative survival of lung cancer with onset in 2011-2014, 2015-2017 and 2018-2020 were calculated using the cohort, complete and period methods, respectively. RESULTS: There were 23,043 patients diagnosed with lung cancer in seven registries between 2011 and 2020, with an age-standardized incidence rate (ASIR) of 37.7/100,000. The males ASIR increased from 51.1/100,000 to 60.5/100,000 with an annual percentage change (APC) of 1.5%. However, females ASIR increased faster than males, with an APC of 5.7% in 2011-2017 and 21.0% in 2017-2020. Compared with 2011, the average onset age of males and females in 2020 was 1.5 years and 5.9 years earlier, respectively. Moreover, the proportion of adenocarcinoma has increased, while squamous cell carcinoma and small cell carcinoma have decreased over the past decade. The 5-year relative survival of lung cancer increased from 13.8 to 23.7%, with a greater average increase in females than males (8.7% and 2.6%). The 5-year relative survival of adenocarcinoma, squamous cell carcinoma and small cell carcinoma reached 47.1%, 18.3% and 6.9% in 2018-2020, respectively. CONCLUSIONS: The incidence of lung cancer in Fujian Province is on the rise, with a significant rise in adenocarcinoma, a younger age of onset and the possibility of overdiagnosis. Thus, Fujian Province should strengthen the prevention and control of lung cancer, giving more attention to the prevention and treatment of lung cancer in females and young populations.

Electronic eye and electronic tongue data fusion combined with a GETNet model for the traceability and detection of Astragalus.

BACKGROUND: Astragalus is a widely used traditional Chinese medicine material that is easily confused due to its quality, price and other factors derived from different origins. This article describes a novel method for the rapid tracing and detection of Astragalus via the joint application of an electronic tongue (ET) and an electronic eye (EE) combined with a lightweight convoluted neural network (CNN)-transformer model. First, ET and EE systems were employed to measure the taste fingerprints and appearance images, respectively, of different Astragalus samples. Three spectral transform methods - the Markov transition field, short-time Fourier transform and recurrence plot - were utilized to convert the ET signals into 2D spectrograms. Then, the obtained ET spectrograms were fused with the EE image to obtain multimodal information. A lightweight hybrid model, termed GETNet, was designed to achieve pattern recognition for the Astragalus fusion information. The proposed model employed an improved transformer module and an improved Ghost bottleneck as its backbone network, complementarily utilizing the benefits of CNN and transformer architectures for local and global feature representation. Furthermore, the Ghost bottleneck was further optimized using a channel attention technique, which boosted the model's feature extraction effectiveness. RESULTS: The experiments indicate that the proposed data fusion strategy based on ET and EE devices has better recognition accuracy than that attained with independent sensing devices. CONCLUSION: The proposed method achieved high precision (99.1%) and recall (99.1%) values, providing a novel approach for rapidly identifying the origin of Astragalus, and it holds great promise for applications involving other types of Chinese herbal medicines. © 2024 Society of Chemical Industry.

γ-Glutamyl-transpeptidase CsGGT2 functions as light-activated theanine hydrolase in tea plant (Camellia sinensis L.).

Theanine is an important secondary metabolite endowing tea with umami taste and health effects. It is essential to explore the metabolic pathway and regulatory mechanism of theanine to improve tea quality. Here, we demonstrated that the expression patterns of CsGGT2 (γ-glutamyl-transpeptidase), participated in theanine synthesis in vitro in our previous research, are significantly different in the aboveground and underground tissues of tea plants and regulated by light. Light up-regulated the expression of CsHY5, directly binding to the promoter of CsGGT2 and acting as an activator of CsGGT2, with a negative correlation with theanine accumulation. The enzyme activity assays and transient expression in Nicotiana benthamiana showed that CsGGT2, acting as bifunctional protein, synthesize and degrade theanine in vitro and in planta. The results of enzyme kinetics, Surface plasmon resonance (SPR) assays and targeted gene-silencing assays showed that CsGGT2 had a higher substrate affinity of theanine than that of ethylamine, and performed a higher theanine degradation catalytic efficiency. Therefore, light mediates the degradation of theanine in different tissues by regulating the expression of the theanine hydrolase CsGGT2 in tea plants, and these results provide new insights into the degradation of theanine mediated by light in tea plants.

Vps33B in Dendritic Cells Regulates House Dust Mite-Induced Allergic Lung Inflammation.

Dendritic cells (DCs) are the most specialized APCs that play a critical role in driving Th2 differentiation, but the mechanism is not fully understood. Here we show that vacuolar protein sorting 33B (Vps33B) plays an important role in this process. Mice with Vps33b-specific deletion in DCs, but not in macrophages or T cells, were more susceptible to Th2-mediated allergic lung inflammation than wild-type mice. Deletion of Vps33B in DCs led to enhanced CD4+ T cell proliferation and Th2 differentiation. Moreover, Vps33B specifically restrained reactive oxygen species production in conventional DC1s to inhibit Th2 responses in vitro, whereas Vps33B in monocyte-derived DCs and conventional DC2s was dispensable for Th2 development in asthma pathogenesis. Taken together, our results identify Vps33B as an important molecule that mediates the cross-talk between DCs and CD4+ T cells to further regulate allergic asthma pathogenesis.

HDACs/mTOR inhibitor synergizes with pyrotinib in HER2-positive pancreatic cancer through degradation of mutant P53.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), as a highly lethal malignancy with high mortality, lacks of effective treatment. Canonical therapeutic targets in PDAC demand further verification among which HER2 receptor tyrosine kinase inhibitor pyrotinib as treatment targets has not be decided. METHODS: Anti-PDAC efficacy of pyrotinib was evaluated both in vitro and in vivo using both cell lines and patient-derived xenografts. By screening a large-scale library of 1453 compounds, we identified HDACs/mTOR inhibitor 1 as a promising candidate to synergize with pyrotinib. The combination therapy was evaluated in vitro and in vivo in multiple cell lines and animal models. Furthermore, RNA-seq analysis was performed to reveal the latent molecular mechanism of combination therapy. RESULTS: In our study, pyrotinib monotherapy was found to be inefficient to anti-PDAC which exhibited limited anti-proliferation effect in vitro and in vivo. Through therapy combined with HDACs/mTOR inhibitor 1, pyrotinib triggered intense apoptosis in PDAC both in cell lines and animal models. Mechanistic analyses revealed that mutant P53 degradation mediated by HDAC inhibition synergized with HER2 and mTOR inhibition. CONCLUSIONS: In conclusion, identification of HDACs/mTOR inhibitor as a synergistic inhibitor, provides a potent therapeutic strategy that targets HER2-positive pancreatic cancer.

The effect of patient perceived involvement on patient loyalty in primary care: The mediating role of patient satisfaction and the moderating role of the family doctor contract service.

BACKGROUND: The Chinese government has taken many incentives to promote the implementation of the family doctor (FD) contract service; however, whether primary health care providers establishing a strong relationship with patients that shapes their loyalty is still unknown. Under this circumstance, drawing the public attention to patient loyalty in primary care and clarifying the underlying mechanism of loyalty is imperative to the development of primary care. OBJECTIVE: To analyse the effect of patient perceived involvement on patient loyalty in primary care, investigate the mediating role of patient satisfaction, and explore the moderating role of the FD contract service on the relationship between patient perceived involvement and patient loyalty. METHODS: A cross-sectional questionnaire survey of patients in primary health facilities was conducted in Jilin province of China. Participants comprised 1334 patients selected via a multi-stage sampling method. RESULTS: Patient perceived involvement not only had a direct positive impact on patient loyalty but also had an indirect effect on patient loyalty via patient satisfaction. Furthermore, for patients who contracted with FDs, patient perceived involvement had a higher direct effect and indirect effect on patient loyalty when compared with patients who did not contract with FDs. CONCLUSIONS: Our findings suggest that health managers should encourage patients to participate in medical visits to improve patient satisfaction. Additionally, customised and tailored health services that meet individuals' specific needs and preferences should be designed and implemented to attract more patients to contract the FD contract service.

A Novel Molecular Signature of Cancer-Associated Fibroblasts Predicts Prognosis and Immunotherapy Response in Pancreatic Cancer.

Cancer-associated fibroblasts (CAFs), a prominent population of stromal cells, play a crucial role in tumor progression, prognosis, and treatment response. However, the relationship among CAF-based molecular signatures, clinical outcomes, and tumor microenvironment infiltration remains largely elusive in pancreatic cancer (PC). Here, we collected multicenter PC data and performed integrated analysis to investigate the role of CAF-related genes (CRGs) in PC. Firstly, we demonstrated that α-SMA+ CAFs were the most prominent stromal components and correlated with the poor survival rates of PC patients in our tissue microarrays. Then, we discriminated two diverse molecular subtypes (CAF clusters A and B) and revealed the significant differences in the tumor immune microenvironment (TME), four reported CAF subpopulations, clinical characteristics, and prognosis in PC samples. Furthermore, we analyzed their association with the immunotherapy response of PC patients. Lastly, a CRG score was constructed to predict prognosis, immunotherapy responses, and chemosensitivity in pancreatic cancer patients. In summary, these findings provide insights into further research targeting CAFs and their TME, and they pave a new road for the prognosis evaluation and individualized treatment of PC patients.

Guest-Binding-Induced Interhetero Hosts Charge Transfer Crystallization: Selective Coloration of Commonly Used Organic Solvents.

Unprecedented interheteromacrocyclic hosts charge transfer (CT) crystals were generated by cooling organic solutions containing p-dimethoxybenzene-constituted pillar[5]arene (P5A) and p-benzoquinone-constituted pillar[5]quinone (P5Q). Despite the weak CT interaction known between p-dimethoxybenzene and p-benzoquinone and the lack of formation of CT complexes between P5A and P5Q in the solution phase, CT cocrystals between P5A and P5Q were formed with solvent molecules included into the hosts' cavities. Such a cocrystallization arises from an elegant synergy between the CT interaction and solvent-binding-promoted crystallization. The interhetero hosts CT crystals were studied by optical and electron microscopic techniques, X-ray powder diffraction, solid-state NMR, UV-vis, IR spectroscopic studies, and X-ray single-crystal studies. The solvent complexation was critical for formation of the supramolecular CT microcrystals. The CT absorption bands faded upon removing the solvent molecules under vacuum, but they could be recovered by reuptake of the solvent molecules. Intriguingly, the CT absorption bands and uptake kinetics are distinguishably different for various organic solvents, thus providing a unique way to distinguish between different commonly used chemicals.

The Aquaporin TaPIP2;10 Confers Resistance to Two Fungal Diseases in Wheat.

Plants employ aquaporins (AQPs) of the plasma membrane intrinsic protein (PIP) family to import environmental substrates, thereby affecting various processes, such as the cellular responses regulated by the signaling molecule hydrogen peroxide (H2O2). Common wheat (Triticum aestivum) contains 24 candidate members of the PIP family, designated as TaPIP1;1 to TaPIP1;12 and TaPIP2;1 to TaPIP2;12. None of these TaPIP candidates have been characterized for substrate selectivity or defense responses in their source plant. Here, we report that T. aestivum AQP TaPIP2;10 facilitates the cellular uptake of H2O2 to confer resistance against powdery mildew and Fusarium head blight, two devastating fungal diseases in wheat throughout the world. In wheat, the apoplastic H2O2 signal is induced by fungal attack, while TaPIP2;10 is stimulated to translocate this H2O2 into the cytoplasm, where it activates defense responses to restrict further attack. TaPIP2;10-mediated transport of H2O2 is essential for pathogen-associated molecular pattern-triggered plant immunity (PTI). Typical PTI responses are induced by the fungal infection and intensified by overexpression of the TaPIP2;10 gene. TaPIP2;10 overexpression causes a 70% enhancement in wheat resistance to powdery mildew and an 86% enhancement in resistance to Fusarium head blight. By reducing the disease severities, TaPIP2;10 overexpression brings about >37% increase in wheat grain yield. These results verify the feasibility of using an immunity-relevant AQP to concomitantly improve crop productivity and immunity.

Survival of cancer patients in Fujian, Southeast China: a population-based cancer registry study.

Survival rates are usually used to evaluate the effect of cancer treatment and prevention. No study has focused on the characteristic of population-based cancer survival in Fujian, which is regarded as one of the high-risk areas of cancer in China. This study aims to analyze the 5-year relative survival of patients in Fujian Province using population-based cancer registry data. A total of 8 population-based registries in Fujian Province reported cancer cases diagnosed in 2012-2014. Relative survival was calculated as the ratio between observed survival and expected survival. The 5-year relative survival for all cancers combined was 36.19% and the age-standardized 5-year relative survival for all patients was 31.80%. Females had higher relative survival than males (38.90% and 27.00%). The patients in urban areas had higher relative survival than those in rural areas (32.34% and 31.29%). Lung, gastric, liver, colorectal, and esophageal cancers were the five most common cancers, with 5-year relative survival below 50%. This is the first study that evaluated the population-based cancer relative survival in Fujian, China. Our study suggests that the overall survival of cancer patients in Fujian Province is poor. Furthermore, the results of this study can be used as a baseline for further research in Fujian, and provide important evidence for cancer etiology research.

Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis.

Dendritic cells (DCs) play pivotal roles in maintaining intestinal homeostasis, but how the DCs regulate diverse immune networks on homeostasis breakdown remains largely unknown. Here, we report that, in response to epithelial barrier disruption, colonic DCs regulate the differentiation of type 1 regulatory T (Tr1) cells through p38α-dependent IL-27 production to initiate an effective immune response. Deletion of p38α in DCs, but not in T cells, led to increased Tr1 and protected mice from dextran sodium sulfate-induced acute colitis and chronic colitis-associated colorectal cancer. We show that higher levels of IL-27 in p38α-deficient colonic cDC1s, but not cDC2s, were responsible for the increase of Tr1 cells. Moreover, p38α-dependent IL-27 enhanced IL-22 secretion from intestinal group 3 innate lymphoid cells and protected epithelial barrier function. In p38α-deficient DCs, the TAK1-MKK4/7-JNK-c-Jun axis was hyperactivated, leading to high IL-27 levels, and inhibition of the JNK-c-Jun axis suppressed IL-27 expression. ChIP assay revealed direct binding of c-Jun to the promoter of Il27p28, which was further enhanced in p38α-deficient DCs. In summary, here we identify a key role for p38α signaling in DCs in regulating intestinal inflammatory response and tumorigenesis, and our finding may provide targets for the treatment of inflammatory intestinal diseases.

Identification of differentially expressed genes associated with aluminum resistance in the soybean plant.

Aluminum (Al) toxicity is a major limitation to crop production in countries where acidic soil is abundant. In China, soybean production is constrained by Al stress-induced toxicity. As such, there is growing interest to develop Al-resistant varieties. In the present study, we sought to determine potential genes, functions and pathways for screening and breeding of Al-resistant varieties of soybean. First, we mined the E-GEOD-18517 dataset and identified 729 differentially expressed genes (DEGs) between untreated and Al-treated groups. Next, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathways enrichment analysis and observed that most of the screened genes were mainly enriched in defense response, plasma membrane and molecular transducer activity. They were also enriched in three important pathways, the phenylpropanoid biosynthesis, plant-pathogen interaction, and cutin, suberine and wax biosynthesis. Utilizing weighted gene co-expression network analysis of 815 DEGs screened by Venn diagram, we identified DEGs that were the most disparate between treated and untreated groups. LOC100793667 (probable protein phosphatase 2C 60, GLYMA_17G223800), LOC100780576 (ethylene-responsive transcription factor 1B, GLYMA_02G006200), and LOC100785578 (protein ESKIMO 1, GLYMA_02G258000) were the most differentially expressed, which were consistent with the qRT-PCR results. As these genes are known to participate in essential functions, such as cell junction and phenylpropanoid biosynthesis, these genes may be important for breeding Al-resistant varieties. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01018-x.

The relationship between ground reaction force in sit-to-stand movement and lower extremity function in community-dwelling Japanese older adults using long-term care insurance services.

[Purpose] The purpose of this study was to investigate which of the four chair-rising methods has low-load and the highest success rate, and whether the GRF parameters in that method are useful for measuring lower extremity function among physically frail Japanese older adults. [Subjects and Methods] Fifty-two individuals participated in this study. The participants voluntarily attempted four types of Sit-to-stand test (one variation without and three variations with the use of their arms). The following parameters were measured: peak reaction force (F/w), two force development rate parameters (RFD1.25/w, RFD8.75/w) and two time-related parameters (T1, T2). Three additional commonly employed clinical tests (One-leg balance with eyes open, Timed up and go and 5-meter walk test) were also conducted. [Results] "Hands on a chair" chair-rising method produced the highest success rate among the four methods. All parameters were highly reliable between testing occasions. T2 showed strongly significant associations with Timed up and go and 5-meter walk test in males. RFD8.75/w showed significant associations with Timed up and go and 5-meter walk test in females. [Conclusion] Ground reaction force parameters in the Sit-to-stand test are a reliable and useful method for assessment of lower extremity function in physically frail Japanese older adults.

Establishment and characterization of a novel hypopharyngeal squamous cell carcinoma cell line CZH1 with genetic abnormalities.

Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among head and neck squamous cell carcinomas. The lack of available tumor cell lines poses a significant obstacle to the development of efficient treatments for HPSCC. In this study, we successfully established a novel cell line, named CZH1, from the postcricoid region of a Chinese male patient with a T3N0M0 HPSCC. Short tandem repeat analysis confirmed the uniqueness of CZH1. The cell line was characterized by its phenotypes, biomarkers, and genetics. Importantly, CZH1 cells retained the typical features of epithelial malignancy, similar to the primary tumor tissue. Furthermore, CZH1 demonstrated a greater capacity for invasion and increased susceptibility to irradiation in comparison to FaDu, which is the most commonly used HPSCC cell line. Whole-exome sequencing analysis revealed that CZH1 cells had typical genomic features of HNSCC, including mutations of TP53 and amplifications of multiple transcripts. Therefore, our newly developed CZH1 cell line could serve as an efficient tool for the in vitro investigation of the etiology, pathogenesis, and preclinical treatment of HPSCC.