A 3'-pre-tRNA-derived small RNA tRF-1-Ser regulated by 25(OH)D promotes proliferation and stemness by inhibiting the function of MBNL1 in breast cancer.

BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.

Vanadium-doped metal-organic framework@Znln2S4 core-shell heterojunction-attenuated photoelectrochemical immunoassay.

Considering that cancer has become the second leading cause of death in humans, it is essential to develop an analytical approach that can sensitively detect tumor markers for early detection. We report an attenuated photoelectrochemical (PEC) immunoassay based on the organic-inorganic heterojunction 10MIL-88B(FeV)/ZnIn2S4 (10M88B(FeV)/ZIS) as a photoactive material for monitoring carcinoembryonic antigen (CEA). The 10M88B(FeV)/ZIS heterojunctions have excellent light-harvesting properties and high electrical conductivity, which are attributed to the advantages of both organic and inorganic semiconductors, namely, remarkable photogenerated carrier separation efficiency and long photogenerated carrier lifetime. Horseradish peroxidase (HRP) in the presence of H2O2 can catalyze 3,3'-diaminofenamide (DAB) producing brown precipitates (oxDAB), which is then loaded onto the 10M88B(FeV)/ZIS heterojunction to reduce the photocurrent and enable the quantitative detection of CEA. Under optimal conditions, the photocurrent values of the PEC biosensor are linearly related to the logarithm of the CEA concentrations, ranging from 0.01 ng mL-1 to 100 ng mL-1 with a detection limit (LOD) of 4.0 pg mL-1. Notably, the accuracy of the PEC biosensor is in agreement with that of the human CEA enzyme-linked immunosorbent assay (ELISA) kit.

Surface plasmon resonance-enhanced photoelectrochemical immunoassay with Cu-doped porous Bi2WO6 nanosheets.

The development of rapid screening sensing platforms to improve pre-screening mechanisms in community healthcare is necessary to meet the significant need for portable testing in biomarker diagnostics. Here, we designed a portable smartphone-based photoelectrochemical (PEC) immunoassay for carcinoembryonic antigen (CEA) detection using Cu-doped ultrathin porous Bi2WO6 (CuBWO) nanosheets as the photoactive material. The CuBWO nanosheets exhibit a fast photocurrent response and excellent electrical transmission rate under UV light due to their surface plasmon resonance effect (SPR). The method uses glucose oxidase-labeled secondary antibody as a signal indicator for sandwich-type immune conjugation. In the presence of the target CEA, the electrons and holes generated at the surface of the photo-excited ultrathin porous CuBWO were rapidly consumed by the production of H2O2 from glucose oxidase oxidizing glucose, resulting in a weakened photocurrent signal. The photocurrent intensity increased logarithmically and linearly with increasing CEA concentration (0.02-50 ng mL-1), with a detection limit of 15.0 pg mL-1 (S/N = 3). The system provides a broader idea for inferring the electron-hole transport mechanism in ultrathin porous nanosheet layer materials and developing efficient PEC sensors.

Epigenetic modification of TWIST1 in macrophages promotes hypertension-induced atherosclerotic plaque instability.

It is accepted that hypertension is a major, independent risk factor for atherosclerotic cardiovascular ischemic events, which are mainly attributed to the formation of unstable, vulnerable atherosclerotic lesions. But the mechanisms by which hypertension aggravates atherosclerosis (AS) through increased macrophage recruitment are unknown. It has been reported that TWIST1 can regulate the shear stress of blood flow in endothelial cells to promote the development of atherosclerosis, but the function of TWIST1 in macrophage recruitment during hypertension remains undefined. Here, the roles of TWIST1 in macrophage activation during N w -nitro-l-arginine-methyl ester (L-NAME; NO-synthase (NOS) inhibitor)-induced hypertension were investigated in ApoE-/- mice fed a high-fat diet (HFD) and RAW264.7 cells treated with oxidized low-density lipoprotein(ox-LDL). Oil Red O staining and hematoxylin and eosin staining were adopted to analyze atherosclerotic lesions and plaque instability. Chromatin immunoprecipitation (ChIP)-PCR was used to explore whether Lysine-specific histone demethylase 1A (LSD1/KDM1A) and Variegated suppressor 3-9 homolog 1 (SUV39H1) could regulate histone modification of the TWIST1 promoter. We reported that L-NAME increased the expression of TWIST1 in the aortic tissues of ApoE-/- mice fed a high-fat diet (HFD) and RAW264.7 cells treated with ox-LDL. TWIST1 accelerated the development of an unstable atherosclerotic phenotype by promoting macrophage activation, inflammatory factor secretion, macrophage polarization, and lipid phagocytosis. Moreover, we found that H3K9me2 and H3K9me3 in the TWIST1 promoter could be coregulated by LSD1 and SUV39H1, and this process was modulated by CK2α. Taken together, these results revealed that TWIST1 in macrophages is a critical factor that mediates foam cell formation and enhances atherosclerotic plaque vulnerability during hypertension, and targeting TWIST1 may be a promising new therapeutic approach for delaying the progression of AS in hypertension.

Smartphone-based photoelectrochemical immunoassay for carcinoembryonic antigen based on BiOCl/CuBi2O4 heterojunction.

Photoelectrochemical (PEC) immunoassay has been widely developed for biomarker detection, but most include heavy and expensive instruments that are not suited for portable and on-site detection. In this work, the PEC immunoassay platform for mobile phones was reported for flexible, rapid, low-cost detection of carcinoembryonic antigen (CEA). The PEC detection platform was successfully composed of disposable screen-printed carbon electrodes, a micro-electrochemical workstation, a flashlight (the excitation light source), and a smartphone with a companion software with a micro-electrochemical workstation for rapid and on-site detection of target biomarkers. In this portable smartphone-based PEC system, the S-scheme heterojunction BiOCl/CuBi2O4 was effectively excited due to the efficient electron transfer rate and excellent photocurrent response under visible light. Specifically, the sandwich-type immunoreaction for capturing target biomarkers introduced alkaline phosphatase (ALP) labeled gold nanoparticles (Au NPs). The addition of CEA increased the ascorbic acid (AA) content and enhanced the photocurrent. The proposed immunoassay presented a good linear with the logarithm of CEA concentrations range within 0.01-40 ng mL-1, and the detection limit of 3.5 pg mL-1 (S/N = 3). Therefore, the portable detection platform offered an implementable approach to the development of miniaturized and portable photoelectrochemical detectors and on-site detection technology.

Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer.

PURPOSE: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. METHODS: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. RESULTS: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. CONCLUSION: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.

A novel TOX3-WDR5-ABCG2 signaling axis regulates the progression of colorectal cancer by accelerating stem-like traits and chemoresistance.

The eradication of cancer stem cells (CSCs) with drug resistance confers the probability of local tumor control after chemotherapy or targeted therapy. As the main drug resistance marker, ABCG2 is also critical for colorectal cancer (CRC) evolution, in particular cancer stem-like traits expansion. Hitherto, the knowledge about the expression regulation of ABCG2, in particular its upstream transcriptional regulatory mechanisms, remains limited in cancer, including CRC. Here, ABCG2 was found to be markedly up-regulated in CRC CSCs (cCSCs) expansion and chemo-resistant CRC tissues and closely associated with CRC recurrence. Mechanistically, TOX3 was identified as a specific transcriptional factor to drive ABCG2 expression and subsequent cCSCs expansion and chemoresistance by binding to -261 to -141 segments of the ABCG2 promoter region. Moreover, we found that TOX3 recruited WDR5 to promote tri-methylation of H3K4 at the ABCG2 promoter in cCSCs, which further confers stem-like traits and chemoresistance to CRC by co-regulating the transcription of ABCG2. In line with this observation, TOX3, WDR5, and ABCG2 showed abnormal activation in chemo-resistant tumor tissues of in situ CRC mouse model and clinical investigation further demonstrated the comprehensive assessment of TOX3, WDR5, and ABCG2 could be a more efficient strategy for survival prediction of CRC patients with recurrence or metastasis. Thus, our study found that TOX3-WDR5/ABCG2 signaling axis plays a critical role in regulating CRC stem-like traits and chemoresistance, and a combination of chemotherapy with WDR5 inhibitors may induce synthetic lethality in ABCG2-deregulated tumors.

Ultrathin mesoporous BiOCl nanosheets-mediated liposomes for photoelectrochemical immunoassay with in-situ signal amplification.

Designing new biochemical sensors and achieving selectivity and high-sensitivity analysis is one of main research directions for immunoassays. Herein, a liposome-amplification photoelectrochemical (PEC) immunoassay was developed using ultrathin mesoporous bismuth chloride oxide nanosheets (BiOCl MSCN) for the highly selective and sensitive detection of carcinoembryonic antigen (CEA). Based on good photocurrent response of BiOCl MSCN toward dopamine, a liposome-conjugated secondary antibody loaded with dopamine was added for specific recognition in the presence of CEA. After the lysis treatment, the liberated dopamine was injected into the three-electrode electrolytic cell to enhance the photocurrent of BiOCl MSCN. Under the optimized conditions, the constructed liposome-mediated PEC immunoassay showed high sensitivity against CEA, with a dynamic response in the linear range of 0.05 ng mL-1 to 100 ng mL-1 and a detection limit of 35 pg mL-1. The present study proposes a new approach to the liposome-mediated PEC immunoassay constructed on ultrathin mesoporous BiOCl nanosheets, which can be used to target further the study of the sensing mechanism.

High-entropy effect with hollow (ZnCdFeMnCu)xS nanocubes for photoelectrochemical immunoassay.

High entropy (HE) compounds with chemically disordered multi-cation structures have become a hot research topic because of their fascinating "cocktail effect". However, high entropy effect with the efficient photoelectric response has not been reported for photoelectrochemical (PEC) immunoassays. Herein, an innovative PEC immunoassay for the sensitive detection of prostate-specific antigen (PSA) was ingeniously constructed using hollow nanocubic (ZnCdFeMnCu)xS photoactive matrices with high entropic effect via the cation exchange. Initially, a sandwich-type immunoreaction has behaved using dopamine-loaded liposome labeled with anti-PSA secondary antibodies. In the presence of PSA, addition of Triton X-100 caused the liposomal cleavage to release dopamine, which was then detected as a reduced photocurrent on (ZnCdFeMnCu)xS-based photoelectrode. Under optimal condition, the PEC immunoassay showed good photocurrent responses toward target PSA with the dynamic linear range of 0.1-50 ng mL-1 with a limit of detection of 34.1 pg mL-1. Significantly, this system can provide a new platform for the development of PEC immunoassays by coupling with high-entropy photoactive materials.

Nanoparticle albumin-bound paclitaxel-based neoadjuvant regimen: A promising treatment option for HER2-low-positive breast cancer.

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.

Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.

BACKGROUND: CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1). METHODS: In this study, we recruited five patients who relapsed after CD19-targeted CAR-T. CD19- and CD22-CAR lentivirus-transfected T cells were cultured separately and mixed before infusion in an approximate ratio of 1:1. The total dose range of CD19 and CD22 CAR-T was 4.3 × 106-1.5 × 107/kg. Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells. RESULTS: After CART2, all five patients had minimal residual disease (MRD)-negative complete remission (CR). The 6- and 12-month overall survival (OS) rates were 100%. The median follow-up time was 26.3 months. Three of the five patients bridged to consolidated allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CART2 and remained in MRD-negative CR at the cut-off time. In patient No. 3 (pt03), CAR-T cells were still detected in the peripheral blood (PB) at 347 days post-CART2. Cytokine release syndrome (CRS) only occurred with a grade of ≤ 2, and no patients experienced symptoms of neurologic toxicity during CART2. CONCLUSIONS: Mixed infusion of CD19- and CD22-targeted CAR-T cells is a safe and effective regimen for children with B-ALL who relapse after prior CD19-targeted CAR-T therapy. Salvage CART2 provides an opportunity for bridging to transplantation and long-term survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000032211. Retrospectively registered: April 23, 2020.

Prognostic analysis of three forms of Ki-67 in patients with breast cancer with non-pathological complete response before and after neoadjuvant systemic treatment.

BACKGROUND: Patients who do not achieve a pathological complete response (pCR) after neoadjuvant systemic treatment (NST) have a significantly worse prognosis. A reliable predictor of prognosis is required to further subdivide non-pCR patients. To date, the prognostic role in terms of disease-free survival (DFS) between the terminal index of Ki-67 after surgery (Ki-67T ) and the combination of the baseline Ki-67 at biopsy before NST (Ki-67B ) and the percentage change in Ki-67 before and after NST (Ki-67C ) has not been compared. AIM: This study aimed to explore the most useful form or combination of Ki-67 that can provide prognostic information to non-pCR patients. PATIENTS AND METHODS: We retrospectively reviewed 499 patients who were diagnosed with inoperable breast cancer between August 2013 and December 2020 and received NST with anthracycline plus taxane. RESULTS: Among all the patients, 335 did not achieve pCR (with a follow-up period of ≥1 year). The median follow-up duration was 36 months. The optimal cutoff value of Ki-67C to predict a DFS was 30%. A significantly worse DFS was observed in patients with a low Ki-67C (p < 0.001). In addition, the exploratory subgroup analysis showed relatively good internal consistency. Ki-67C and Ki-67T were considered as independent risk factors for DFS (both p < 0.001). The forecasting model combining Ki-67B and Ki-67C showed a significantly higher area under the curve at years 3 and 5 than Ki-67T (p = 0.029 and p = 0.022, respectively). CONCLUSIONS: Ki-67C and Ki-67T were good independent predictors of DFS, whereas Ki-67B was a slightly inferior predictor. The combination of Ki-67B and Ki-67C is superior to Ki-67T for predicting DFS, especially at longer follow-ups. Regarding clinical application, this combination could be used as a novel indicator for predicting DFS to more clearly identify high-risk patients.

MED27 plays a tumor-promoting role in breast cancer progression by targeting KLF4.

The mediator complex usually cooperates with transcription factors to be involved in RNA polymerase II-mediated gene transcription. As one component of this complex, MED27 has been reported in our previous studies to promote thyroid cancer and melanoma progression. However, the precise function of MED27 in breast cancer development remains poorly understood. Here, we found that MED27 was more highly expressed in breast cancer samples than in normal tissues, especially in triple-negative breast cancer, and its expression level was elevated with the increase in pathological stage. MED27 knockdown in triple-negative breast cancer cells inhibited cancer cell metastasis and stemness maintenance, which was accompanied by downregulation of the expression of EMT- and stem traits-associated proteins, and vice versa in non-triple-negative breast cancer. Furthermore, MED27 knockdown sensitized breast cancer cells to epirubicin treatment by inducing cellular apoptosis and reducing tumorsphere-forming ability. Based on RNA-seq, we identified KLF4 as the possible downstream target of MED27. KLF4 overexpression reversed the MED27 silencing-mediated arrest of cellular metastasis and stemness maintenance capacity in breast cancer in vitro and in vivo. Mechanistically, MED27 transcriptionally regulated KLF4 by binding to its promoter region at positions -156 to +177. Collectively, our study not only demonstrated the tumor-promoting role of MED27 in breast cancer progression by transcriptionally targeting KLF4, but also suggested the possibility of developing the MED27/KLF4 signaling axis as a potential therapeutic target in breast cancer.

Volume change rate before and after neoadjuvant systemic therapy of breast cancer is an efficacious evaluation index to predict pathological complete response.

Neoadjuvant systemic therapy (NST) is widely applied in breast cancer treatment, but individuals respond differently to the same NST regimen. It is unclear which patients should adjust their NST regimen and what such an adjustment should be, especially for patients with radiologically partial response (PR). This study aimed to identify a quantitative efficacy evaluation index to evaluate the therapeutic effect of NST. 164 patients were enrolled in this study received four cycles of epirubicin and cyclophosphamide (EC), followed by four cycles of taxanes with trastuzumab [T(H)], if needed. Of patients with a volume change rate of EC treatment (δV1) below 0.80, more than half benefited from subsequent T(H) treatment compared with EC treatment. Importantly, for δV1 of 0.80 and higher, patients' subsequent T(H) treatment was not as efficient as previous EC treatment and they have a lower pathological complete response (pCR) rate. Across all patients, nanoparticle albumin-bound paclitaxel had a numerically higher pCR rate over other taxanes in patients with triple-negative breast cancer. This study showed that the volume change rate is better than the diameter change rate in monitoring the therapeutic effect of NST. Furthermore, δV1 is a good quantitative efficacy evaluation index to distinguish patients resistant to EC treatment and predict the pCR rate and guide the adjustment of individualized NST regimens.

Comparison of clinicopathological characteristics and response to neoadjuvant systemic therapy in patients with HER2-low-positive and HER2-zero breast cancer.

Previous studies have observed that human epidermal growth factor receptor 2 (HER2)-low-positive patients and HER2-zero patients have different prognoses. This study was conducted to investigate whether there are differences in clinicopathological characteristics and the response to neoadjuvant systemic therapy (NST) defined as systemic treatment prior to surgery between HER2-low-positive patients and HER2-zero patients. We retrospectively analyzed the data of patients with HER2-negative breast cancer who received NST at the First Affiliated Hospital of Nanjing Medical University from 2014 to 2021. There were 238 patients with HER2-low-positive status and 198 patients with HER2-zero status. The proportion of hormone receptor (HR)-positive patients in the HER2-low-positive group was significantly higher than that in the HER2-zero group (82.8% vs 52.0%, p < 0.001). The HER2-low-positive group had more patients with low Ki67 expression (23.9% vs 16.2%, p = 0.045), higher mastectomy rate (94.5% vs 88.9%, p = 0.031), and larger pathological tumor size (21.6 vs 17.8 mm, p = 0.028) than the HER2-zero group. However, no significant differences were found in pathologic complete response (pCR) rates between the two groups. We draw a conclusion that patients with HER2-low status and HER2-zero status were not found to have different pCR rates after NST, irrespective of HR status. However, differences were observed in some clinicopathological characteristics between the two groups.

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.

PURPOSE: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS: Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19-/CD22+, one CD19-/CD22-, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients (P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION: CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.[Media: see text].

The protective pattern of chitosan-based active coating on texture stabilization of refrigerated carp fillets from the perspective of proteolysis.

Herein, the protective pattern of chitosan coating enriched with green tea extract on texture stabilization of refrigerated grass carp fillets was explored. In general, higher shear force and lower endogenous enzyme activities were observed in coated fillets, with the max. level of cathepsins and calpain decreasing by 30.2 âˆ¼ 39.6 % when compared to the control during storage. Meanwhile, the coating reduced protein composition changes and accumulation of protein degradation products. According to label-free proteomic analysis, the proteome closer to fresh sample was observed in coated fillets than that of the control, as supported by PCA and hierarchical cluster analysis. Meanwhile, 33 differential proteins involved in tissue structure, protein phosphorylation and protein turnover were further screened out, and most DAPs showed up-regulation in coated fillets compared to the control on day 12. Presumably, the coating modulated endogenous enzyme-induced myofibrillar protein degradation and protein phosphorylation level, thereby stabilizing the texture properties of refrigerated fillets.

Willingness of tobacco farmers to accept compensation for tobacco crop substitution in Lichuan City, China.

OBJECTIVE: This study, conducted in China, explores tobacco farmers' willingness to accept (WTA) compensation for tobacco crop substitution. METHODS: The contingent valuation method was used to elicit farmers' WTA compensation. A face-to-face survey was conducted with 280 tobacco farmers in Lichuan City, China. The standard logit regressions were used to identify the factors that influence farmers' WTA. RESULTS: Without compensation, most of the respondents were unwilling to implement tobacco crop substitution. However, if the government provided compensation, the proportion of respondents' willingness for substitution increased to 86.7%. Male tobacco farmers are more likely to accept a given compensation value than female farmers. Older tobacco farmers have a higher probability of accepting compensation. The number of farmers engaged in tobacco growing in a family is negatively associated with the probability of accepting a given compensation amount. Tobacco farmers with greater confidence in the expected benefits of tobacco crop substitution tend to be more willing to accept compensation. The mean WTA estimate was achieved as US$2020.35/ha/year. CONCLUSIONS: If appropriate compensation is provided for tobacco farmers, there is a potential to implement the tobacco crop substitution policy in the study area.

A prospective, randomized clinical trial of emergency treatment of chemotherapy-induced neutropenia and febrile neutropenia by pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF).

AIMS: As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. METHODS: A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. RESULTS: Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. CONCLUSION: This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.

A novel nomogram containing efficacy indicators to predict axillary pathologic complete response after neoadjuvant systemic therapy in breast cancer.

Background: Neoadjuvant systemic therapy (NST) could make some clinically node-positive (cN+) breast cancer patients achieve axillary pathologic complete response (pCR). This study aimed to identify the patients who are likely to achieve axillary pCR and help surgeons make surgical decisions on the axilla. Methods: The cN+ breast cancer patients who received NST from 2015 to 2021 at The First Affiliated Hospital of Nanjing Medical University were enrolled. Univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed based on the results of multivariate logistic regression analysis to predict the probability of axillary pCR and validated. Results: The axillary pCR was achieved in 208 (38.7%) patients. Patients who had a higher radiological response rate of breast tumor (P = 0.039), smaller longest diameter of positive node after NST (P = 0.028), ER-negative status (P = 0.006), HER2-positive status (P = 0.048) and breast pCR (P < 0.001) were more likely to achieve axillary pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.795 (95% CI: 0.747-0.843), and the calibration curve showed good agreement. Conclusion: A nomogram was constructed to predict the axillary pCR of cN+ patients receiving NST based on baseline and efficacy indicators to assist surgeons in making surgical decisions on the axilla.