Effect of a collagen peptide-fish oil high internal phase emulsion on the printability and gelation of 3D-printed surimi gel inks.

The effect of a high internal phase emulsion (HIPE) on three-dimensional-printed surimi gel inks was studied. Increasing the concentration of collagen peptide decreased the particle size of HIPE droplets and improved the viscoelasticity and stability. For example, when the collagen peptide concentration was 5 wt%, the viscoelasticity of the HIPE was high, as indicated by the presence of small and uniform particles, which formed a monolayer in the outer layer of the oil droplets to form stable a HIPE. A HIPE was used as the filling material to fill the surimi gel network, which reduced the porosity of the network. Surimi protein and peptides have dual emulsifying effects on the stabilization of oil. After adding the emulsion, the texture, gel properties and rheological properties of the surimi were reduced, and its printing adaptability was improved. This study provides new ideas for the production of surimi and its application in 3D printing.

Flavor formation of tilapia byproduct hydrolysates in Maillard reaction.

The Maillard reaction (MR) of tilapia byproduct protein hydrolysates was investigated for the use of byproduct protein as a food ingredient and to mask its fishy odor and bitter flavor. The flavor differences in tilapia byproduct hydrolysates before and after the MR were analyzed to explore the key flavor precursor peptides and amino acids involved in MR. The results suggested that eight key volatile substances, including 2,5-dimethylpyrazine, 2-pentylfuran, hexanal, octanal, nonanal, (E)-2-decenal, decanal, and 1-octen-3-ol contributed most to the MR products group (ROAV > 1). Ten volatile compounds, including 1-octen-3-ol, hexanal, 2-pentylfuran, 2,5-dimethylpyrazine, methyl decanoate, and 2-octylfuran, were the flavor markers that distinguished the different samples (VIP > 1). The four most consumed peptides were VAPEEHPTL, GPIGPRGPAG, KSADDIKKAF, and VWEGQNIVK. Umami peptides and bitter free amino acids (FAAs) were the key flavor precursor peptide and FAAs, respectively. Overall, the hydrolysates of tilapia byproducts with flavor improved by MR are a promising strategy for the production of flavorings.

The tRF-3024b hijacks miR-192-5p to increase BCL-2-mediated resistance to cytotoxic T lymphocytes in Esophageal Squamous Cell Carcinoma.

The limited efficacy of immune checkpoint inhibitors (ICIs) in the treatment of advanced Esophageal Squamous Cell Carcinoma (ESCC) poses a challenge. Recent evidence suggests that tumor cells' insensitivity to cytotoxic T lymphocytes (CTLs) contributes to drug resistance against ICIs. Here, a particular tRNA-derived fragment called tRF-3024b has been identified as playing a significant role in tumor cell resistance to CTLs. Through tRF sequencing (tRF-seq), we observed a high expression of tRF-3024b in ESCC cells that survived co-culture with CTLs. Further in vitro studies demonstrated that tRF-3024b reduced the apoptosis of tumor cells when co-cultured with CTLs. The mechanism behind this resistance involves tRF-3024b promoting the expression of B-cell lymphoma-2 (BCL-2) by sequestering miR-192-5p, a microRNA that would normally inhibit BCL-2 expression. This means that tRF-3024b indirectly enhances the protective effects of BCL-2, reducing apoptosis in tumor cells. Rescue assays confirmed that the suppressive function of tRF-3024b relies on BCL-2. In summary, the tRF-3024b/miR-192-5p/BCL-2 axis sheds light on the crucial role of tRF-3024b in regulating BCL-2 expression. These findings offer valuable insights into strategies to enhance the response of ESCC to CTLs and improve the effectiveness of immunotherapy approaches in treating ESCC.

Serum organophosphate flame retardants and plasticizers in Chinese females of childbearing age: Association with serum reproductive and thyroid hormones.

Organophosphate flame retardants (OPFRs) are extensively used as flame retardants and plasticizers, but their endocrine disrupting potentials have raised concerns. However, the impacts of OPFR exposures on reproductive and thyroid hormones in females remains unclear. In this study, serum concentrations of OPFRs were investigated, and levels of reproductive and thyroid hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone, prolactin (PRL), testosterone (T), and thyroid stimulating hormone, were analyzed in childbearing-age females undergoing in-vitro fertilization treatment from Tianjin, a coastal city in China (n = 319). Tris (2-chloroethyl) phosphate (TCEP) was the predominant OPFR, with a median concentration of 0.33 ng/mL and a detection frequency of 96.6%. In the whole population, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP) were positively associated with T (p < 0.05), while triethyl phosphate (TEP) was negatively associated with LH (p < 0.05) and LH/FSH (p < 0.01). Particularly, TCIPP was negatively associated with PRL in the younger subgroup (age≤30, p < 0.05). Moreover, TCIPP was negatively associated with diagnostic antral follicle counting (AFC) in the mediation analysis by a dominating direct effect (p < 0.01). In conclusion, serum levels of OPFRs were significantly associated with reproductive and thyroid hormone levels and a risk of decreased ovarian reserve in childbearing-age females, with age and body mass index being significant influencing factors.

Different responses to joint exposure to cadmium and zinc depends on the sex in Populus cathayana.

The alarming increase in soil contamination by heavy metals, such as cadmium and zinc demands immediate attention. The dioecious tree Populus cathayana, a phytoremediation plant, plays an important role in rehabilitating heavy metal contaminated areas. In this study, male and female P. cathayana plants were treated with Cd (20 mg kg-1) and different levels of Zn (25, 50, or 100 mg kg-1) to study their physiological responses. The results showed that Cd exposure alone caused stress by inhibiting the growth of both male and female plants. In both males and females, photosynthesis and antioxidant enzymes activities decreased substantially under Cd stress alone. Cd was largely located in the roots, but Zn was present in the shoots of both sexes. Zn supplementation considerably increased the photosynthetic rate from 14.62 % to 60.45 % and also enhanced the antioxidant enzymes activities from 24.11 % to 86.21 %. Zn treatment decreased the translocation ability of Cd compared to the Cd-only treatment, alleviating Cd toxicity. In addition, when sufficient Zn was made available, males showed a high degree of Cd accumulation, low root-to-shoot translocation, elevated antioxidant defense abilities, and an increased photosynthetic rate, while females were less responsive to Cd stress than males. Thus, combined exposure to Cd and Zn caused differential responses in plant growth and physiological processes between males and females P. cathayana. Male plants exhibit better Cd tolerance and accumulation capacity under optimum Zn supplementation. This study increases the fundamental knowledge regarding P. cathayana plants, which can be applied to enhance their remediation capacity in Cd-contaminated soils.

De Novo mutation in Epidermal growth factor receptor (EGFR)-D761Y responding to third generation tyrosine kinase inhibitor Osimertinib: A case report.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) mutations are the most common accurate gene targets. However, the lack of case reports or cohort studies on the exceptionally rare mutations limit the acquisition of deeper insights. PATIENT CONCERNS: A 76-year-old female nonsmoker presented to our hospital with a one-week disease history of cough accompanied by shortness of breath. DIAGNOSIS: Contrast-enhanced CT scan showed right pleural effusion with scattered inflammation and consolidation in the right upper lung. Tumor marker display showed obvious increased. Histopathology of the pulmonary mass combined with Immunohistochemical staining indicated lung adenocarcinoma. Contrast-enhanced magnetic resonance imaging suggested brain metastases. ECT scan showed bone metastasis. The patient was thus diagnosed as right lung adenocarcinoma of stage IV (cT3N3M1c). Next generation sequencing was performed to profile the mutation status of known oncogenic driver mutations, and only EGFR-D761Y in exon 19 (allelic frequency, AF: 0.53%) mutation was found. INTERVENTIONS: The patient was accordingly treated with the third generation EGFR-Epidermal growth factor receptor tyrosine kinase inhibitor (TKI) Osimertinib (80 mg, qd). Accompanied with whole brain radiotherapy (DT3000c Gy/10f) for brain metastases, technetium methylene diphosphonate injection was performed for bone metastases. OUTCOMES: The efficacy of the first-line Osimertinib treatment for 1 month was assessed as PR per RECIST version 1.1. The NSCLC patient harboring EGFR-D761Y mutation detected prior to the EGFR L858R mutation was benefited from the third-generation EGFR-TKI Osimertinib and had a worse prognosis than with other EGFR mutations according to data from previous case reports. CONCLUSIONS: This case reported a NSCLC patient with de novo mutation of EGFR-D761Y responding to third generation TKI Osimertinib.

Modification of the 8th American Joint Committee on Cancer staging system for gallbladder carcinoma to improve prognostic precision.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for gallbladder carcinoma (GBC) came into force since 2018. However, the prognostic precision of this staging system has not been properly assessed. This study aimed to evaluate the latest staging system and suggest modifications to improve its prognostic precision. METHODS: Data of patients with GBC was included from the Surveillance, Epidemiology and End Results (SEER) database (2004-2015) and multicenter database (2010-2017). Baseline clinicopathologic characteristics were recorded including age, sex, race, grade, T category, N category, M category and stage. The Kaplan-Meier method was used to plot survival functions. The prediction power of the AJCC 8th edition and its modified version were evaluated using the concordance index (C-index). RESULTS: A total of 2779 GBC patients were included in the SEER database and 591 were collected from multicenter database. While no significant difference in survival of patients was observed between stages IVA and IVB using the 8th AJCC staging system (p > 0.05), the prognosis of stage IIIA showed a slightly better outcome than stage IIIB (p = 0.046) in the SEER database. In the multicenter database, there was no significant difference between stage IIIA and stage IIIB (p > 0.05). Similarly, no significant difference in the survival of patients between stages IIIA and IIIB was observed when M0 patients with at least 6 lymph nodes (LNs) were analyzed (p > 0.05) for both SEER and multicenter database. On the other hand, a modified staging system was able to stratify patients from stage IIIA, stage IIIB and stage IV (p < 0.001). For the SEER database, the C-indexes of 8th AJCC staging system and that of its modified version were 0.709 and 0.742, respectively. For the multicenter database, the C-index of 8th AJCC staging system and that of our modified version were 0.635 and 0.679, respectively. CONCLUSIONS: The modified 8th staging system proposed in this study can improve the prognostic precision of the 8th AJCC staging system for GBC. We therefore suggest including these modifications in the next update of AJCC staging system for GBC.

Incidence, prevalence, and outcomes of systemic malignancy with bone metastases.

PURPOSE: Evidence on the incidence, prevalence, and outcomes of bone metastases among patients with systemic malignancy is limited. This study aimed to evaluate it using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We collected patients diagnosed with solid malignant tumors deriving outside of the bone, hematologic malignancies, Kaposi sarcoma, lymphoma, and myeloma from the SEER database (from 2010 to 2013). The incidence, prevalence, and outcomes of these systemic malignancies with bone metastases were then analyzed. RESULTS: A total of 67,605 patients with bone metastases at cancer diagnosis were included. The highest rate of bone metastases was observed in patients with small-cell lung cancer at the time of alternative primary site cancer diagnosis. Among 226,816 cases with metastatic disease, cases with breast cancer (65.58%), and prostate cancer (89.60%) had a high incidence proportion (>10%) of identified bone metastases. Patients with additional bone metastases resulting from prostate cancer, breast cancer, and testis cancer presented the best survival time. CONCLUSIONS: Incidence and prognosis differ considerably among bone metastases with different primary malignancy sites. These results may encourage appropriate application of bone imaging.

Study on immunostimulatory activity and extraction process optimization of polysaccharides from Caulerpa lentillifera.

The process of extracting polysaccharides from the green algae Caulerpa lentillifera was studied by single factor experiments and response surface methodology. Additionally, the immunostimulatory activity of Caulerpa lentillifera polysaccharides (CLP) on RAW264.7 mouse macrophage was evaluated by in vitro cell experiments. The results showed that the optimal extraction conditions consisted of ultrasonification for 30 min, extraction time of 9 h, extraction temperature of 100 °C, and a ratio of water to raw material of 40:1. RAW264.7 macrophage exhibited enhanced phagocytosis with no toxic effects after treatment with CLP. In addition, CLP effectively increased the synthesis and secretion of cytokines (IL-6, TNF-α, IL-1ß, and NO), whereby the secretion levels of IL-6, TNF-α, and IL-1ß were 1,840.32 ± 21.03 pg/mL (50 µg/mL), 197.17 ± 3.13 ng/mL (50 µg/mL), and 1,178.35 ± 78.82 pg/mL (25 µg/mL), respectively. The polysaccharides contained in Caulerpa lentillifera have potential value for further development due to their immunological activity.

A benchtop system to assess the feasibility of a fully independent and implantable brain-machine interface.

OBJECTIVE: State-of-the-art invasive brain-machine interfaces (BMIs) have shown significant promise, but rely on external electronics and wired connections between the brain and these external components. This configuration presents health risks and limits practical use. These limitations can be addressed by designing a fully implantable BMI similar to existing FDA-approved implantable devices. Here, a prototype BMI system whose size and power consumption are comparable to those of fully implantable medical devices was designed and implemented, and its performance was tested at the benchtop and bedside. APPROACH: A prototype of a fully implantable BMI system was designed and implemented as a miniaturized embedded system. This benchtop analogue was tested in its ability to acquire signals, train a decoder, perform online decoding, wirelessly control external devices, and operate independently on battery. Furthermore, performance metrics such as power consumption were benchmarked. MAIN RESULTS: An analogue of a fully implantable BMI was fabricated with a miniaturized form factor. A patient undergoing epilepsy surgery evaluation with an electrocorticogram (ECoG) grid implanted over the primary motor cortex was recruited to operate the system. Seven online runs were performed with an average binary state decoding accuracy of 87.0% (lag optimized, or 85.0% at fixed latency). The system was powered by a wirelessly rechargeable battery, consumed ∼150 mW, and operated for >60 h on a single battery cycle. SIGNIFICANCE: The BMI analogue achieved immediate and accurate decoding of ECoG signals underlying hand movements. A wirelessly rechargeable battery and other supporting functions allowed the system to function independently. In addition to the small footprint and acceptable power and heat dissipation, these results suggest that fully implantable BMI systems are feasible.

High glucose upregulates osteopontin expression by FoxO1 activation in macrophages.

Hyperglycemia plays a major role in the development of diabetic macrovascular complications, including atherosclerosis and restenosis, which are responsible for the most of disability and mortality in diabetic patients. Osteopontin (OPN) is an important factor involved in atherogenesis, and hyperglycemia enhances the transcriptional activity of FoxO1 which is closely association with insulin resistance and diabetes. Here, we showed that plasma OPN levels were significantly elevated in type 2 diabetic patients and positively correlated with glycated albumin (GA). The more atherosclerotic lesions were observed in the aorta of diabetic ApoE-/- mice analyzed by Sudan IV staining. High glucose increased both the mRNA and protein expression levels of OPN and inhibited the phosphorylation of FoxO1 in RAW 264.7 cells. Overexpression of WT or constitutively active mutant FoxO1 promoted the expression levels of OPN, while the dominant-negative mutant FoxO1 decreased slightly the expression of OPN. Conversely, knockdown of FoxO1 reduced the expression of OPN. Luciferase reporter assay revealed that high glucose and overexpression of FoxO1 enhanced the activities of the OPN promoter region nt -1918 ~ -713. Furthermore, the interactions between FoxO1 and the OPN promoter were confirmed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). Our results suggest that high glucose upregulates OPN expression via FoxO1 activation, which would play a critical role in the development of diabetic atherogenesis.

Impact of the number of examined lymph nodes on outcomes in patients with lymph node-negative gallbladder carcinoma.

AIM: To determine whether the number of examined lymph nodes (LNs) is correlated with the overall survival of gallbladder carcinoma (GBC) patients. METHODS: Patients were collected from the Surveillance Epidemiology and End Results database (2004-2013) and categorized by the number of LNs into six groups: 1 LN, 2 LNs, 3 LNs, 4 LNs, 5 LNs, and ≥ 6 LNs. Survival curves for overall survival were plotted with a Kaplan-Meier analysis. The log-rank test was used for univariate comparisons. RESULTS: In a cohort of 893 patients, the median number of examined LNs was two for the entire cohort. The survival for the 1 LN group was significantly poorer than those of the stage I and II disease groups and for the entire cohort. By dichotomizing the number of LNs from 1 to 6, we found that the minimum number of LNs that should be examined was four for stage I, four or five for stage II, and six for stage IIIA disease. Therefore, for the entire cohort, the number of examined LNs should be at least six, which is exactly consistent with the American Joint Committee on Cancer criteria. CONCLUSION: The examination of higher numbers of LNs is associated with improved survival after resection surgery for N0 GBC. The guidelines for GBC surgery, which recommend that six LNs be examined at least, are statistically valid and should be applied in clinical practice widely.

Stage III should be subclassified into Stage IIIA and IIIB in the American Joint Committee on Cancer (8th Edition) staging system for pancreatic cancer.

AIM: To ascertain the prognostic role of the T4 and N2 category in stage III pancreatic cancer according to the 8th edition of the American Joint Committee on Cancer (AJCC) classification. METHODS: Patients were collected from the Surveillance Epidemiology and End Results (SEER) database (2004-2013) and were divided into three groups: T(1-3)N2, T4N(0-1), and T4N2. Overall survival (OS) and disease-specific survival (DSS) of patients were evaluated by the Kaplan-Meier method. RESULTS: For the first time, we found a significant difference in OS and DSS between T(1-3)N2/T4N(0-1) and T4N2 but not between T(1-3)N2 and T4N(0-1). A higher grading correlated with a worse prognosis in the T(1-3)N2 and T4N2 groups. CONCLUSION: Patients with stage T4N2 had a worse prognosis than those with stage T(1-3)N2/T4N(0-1) in the 8th edition AJCC staging system for pancreatic cancer. We recommend that stage III should be subclassified into stage IIIA [T(1-3)N2/T4N(0-1)] and stage IIIB (T4N2).

Effects and action mechanisms of sodium fluoride (NaF) on the growth and cephalotaxine production of Cephalotaxus mannii suspension cells.

To explore the effects of NaF on the growth and cephalotaxine production of Cephalotaxus mannii suspension cells, NaF was added into the C mannii cell suspension cultures at day 15 of culture time. It is documented that NaF suppressed cell growth but enhanced cephalotaxine production. The largest yield obtained of cephalotaxine reached to 9.57mg/L when the cultures were treated with an appropriate dosage of 15mg/L NaF, which was 3.7 times that of the control cultures (2.58mg/L). Additionally, NaF markedly enhanced the activity of glucose 6-phosphate dehydrogenase (G6PDH) and reduced the level of hydrogen peroxide (H2O2) of cells. It was also found that NaF weakened the oxidative damage of cell membrane and led to lower content of malonyl dialdehyde (MDA) in NaF-treated cells compared with the control cells. The MDA content of NaF-treated cells decreased 91% compared to the controls. Although lower membrane lipid peroxidation in NaF-treated cells, its membrane permeability was higher than the control cells and showed a high product secret rate. What is more, NaF boosted the activity of phenylalanine ammonium-lyse (PAL), but did not burst a peak of PAL activity in the time curve of PAL activity. These results indicated NaF acted as an inhibitor of the Enbden Parnas (EMP) pathway, not as an elicitor to promote cephalotaxine production.

Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation.

A series of 3-substituted (5c-5f, 6c-6f) and 4-substituted (10a-10g) oxoisoaporphine derivatives were synthesized. It was found that all these synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and most of them could inhibit amyloid ß (Aß) self-induced aggregation with inhibition ratio from 31.8% to 57.6%. The structure-activity relationship studies revealed that the derivatives with higher selectivity on AChE also showed better inhibition on Aß self-induced aggregation. The results from cell toxicity study indicated that most quaternary methiodide salts had higher IC50 values than the corresponding non-quaternary compounds. This study provided potentially important information for further development of oxoisoaporphine derivatives as lead compounds for the treatment of Alzheimer's disease.

Paclitaxel production using co-culture of Taxus suspension cells and paclitaxel-producing endophytic fungi in a co-bioreactor.

The co-culture of the suspension cells of Taxus chinensis var. mairei and its endophytic fungi, Fusarium mairei, in a 20-L co-bioreactor was successfully established for paclitaxel production. The co-bioreactor consists of two-unit tanks (10 L each) with a repairable separate membrane in the center, culturing Taxus suspension cells in one tank and growing fungi in another. By optimizing the co-culture conditions, there was a desirable yield of paclitaxel in Taxus cell cultures. The Taxus cell cultures by co-culture produced 25.63 mg/L of paclitaxel within 15 days; it was equivalent to a productivity of 1.71 mg/L per day and 38-fold higher than that by uncoupled culture (0.68 mg/L within 15 days). The optimum conditions for co-culture in the co-bioreactor were: B5 medium, inoculating fungi when Taxus cells had grown for 5 days in the co-bioreactor, hydrophilic separate membrane in the center of the co-bioreactor, and air flow rate of 1:0.85 v/v/m in fungus cultures.