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Nanoparticle albumin-bound (nab)- paclitaxel has improved uptake by tumor cells in comparison to paclitaxel. The aim of this study was to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin with concurrent image-guidance volume modulated arc therapy (IG-VMAT) for locally advanced cervical cancer (LACC).This single-arm phase I trial followed the standard 3 + 3 dose escalation design. Patients with histologically proven stage IB2-IVA LACC were eligible. IG-VMAT included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and subsequent high dose rate intracavitary brachytherapy (HDR-IBT) at a total doses of 30.0 Gy in 5 fractions, twice a week. Concurrent chemotherapy regimen included weekly cisplatin (40 mg/mA total of 22 patients were enrolled from September 2019 to August 2021. The most common adverse events were grade 1-3 leukopenia, diarrhea, and nausea/vomiting. A total of 4 patients (18.0%) experienced DLT: grade 3 hypokalemia at 33 mg/mIn patients undergoing concurrent IG-VAMT with nab-paclitaxel plus cisplatin for LACC, MTD of nab-paclitaxel was 50 mg/m

α-Antimonene has recently been successfully fabricated in experiment; hence, it is timely to examine how various types of point defects in α-antimonene can affect its novel electronic properties.

Although effective, immune checkpoint blockade induces response in only a subset of cancer patients. There is an urgent need to discover new immune checkpoint targets. Recently, it was found that a class of sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed on the surface of T cells in cancer patients inhibit T cell activation through their intracellular immunosuppressive motifs by recognizing sialic acid-carrying glycans, sialoglycans. However, ligands of Siglecs remain elusive. Here, we report sialylated IgG (SIA-IgG), a ligand to Siglec-7, that is highly expressed in epithelial cancer cells. SIA-IgG binds Siglec-7 directly and inhibits TCR signals. Blocking of either SIA-IgG or Siglec-7 elicited potent antitumor immunity in T cells. Our study suggests that blocking of Siglec-7/SIA-IgG offers an opportunity to enhance immune function while simultaneously sensitizing cancer cells to immune attack.

The incidence of liver cancer is increasing year by year, and how to effectively diagnose early-stage liver cancer and improve the survival rate of liver cancer patients has become one of the current research topics of concern. Aiming at this problem, it is of great significance for the diagnosis of early liver cancer. With the in-depth research on the diagnosis of early-stage liver cancer, the research on growth differentiation factor 15 is gradually carried out, and its performance advantages are of great significance to solve the problem of detection and diagnosis of early-stage liver cancer. This study can improve the accuracy of early diagnosis of liver cancer. The purpose of this paper is to study the application of data mining in the study of clinical value of growth and differentiation factor 15 detection and diagnosis of early liver cancer. In this paper, the data mining algorithm is analyzed, the performance of the algorithm is experimentally analyzed, and the relevant theoretical formulas are used to explain. The results showed that the expression level of GDF-15 was significant in early primary liver cancer (tumor diameter P < 0.01 ), there was a significant difference ( P < 0.01 ) compared with adjacent tissue ( P < 0.01 ). Serum GDF-15 can be used as a tumor marker for predicting early stage liver cancer. The high expression of GDF-15 in early stage liver cancer is an independent risk factor affecting the prognosis of liver cancer patients.

The reported biological effects of cerium dioxide nanoparticles (nCeO2) in soils range from toxic to protective. However, divergences of nCeO2 toxicity in soils of different textures are not known. In this study, the availability of nCeO2 on earthworms (Eisenia foetida) in sandy loam soils and clay soils were discussed, and the biological effects of nCeO2 (0-1000 mg/kg) on earthworms in two soils were investigated. The results showed the bioaccumulation and biological effects of Ce on earthworms in the two soils were inconsistent. The BCR sequential extraction revealed that the major portions of Ce in both soils were in the residual form (98%-99%), and the acid-soluble Ce fraction were greater in clay soils. However, compared with clay soils, nCeO2 was more toxic to earthworms in sandy loam soils as assesses by earthworm biomass, morphology, and antioxidative damage. Thus, the high ecological risk of nCeO2 in sandy loam soils with higher pH and lower clay contents needs to be avoided, being used in agriculture to improve both crop yield and quality.

The reduction in habitat quality (as shown, in part, by the increase in habitat rarity) is an important challenge when protecting the Yunnan snub-nosed monkey. We used the InVEST model to quantitatively analyze the dynamic changes in the habitat of the Yunnan snub-nosed monkey from 1975 to 2022. The results show that in the study period, the degree of habitat degradation increased, with the degradation range at its widest in the south, and the degradation intensity highest in the north, especially along a center “spine” area in the north. Over the latter part of the study period, the habitat quality of most monkey groups improved, which is conducive to the survival and reproduction of the population. However, the habitat quality and monkey populations are still at significant risk. The results provide the basis for formulating the protection of the Yunnan snub-nosed monkey and provide research cases for the protection of other endangered species.

Inborn errors of TLR3-dependent type I IFN immunity in cortical neurons underlie forebrain herpes simplex virus-1 (HSV-1) encephalitis (HSE) due to uncontrolled viral growth and subsequent cell death. We report an otherwise healthy patient with HSE who was compound heterozygous for nonsense (R422*) and frameshift (P493fs9*) RIPK3 variants. Receptor-interacting protein kinase 3 (RIPK3) is a ubiquitous cytoplasmic kinase regulating cell death outcomes, including apoptosis and necroptosis. In vitro, the R422* and P493fs9* RIPK3 proteins impaired cellular apoptosis and necroptosis upon TLR3, TLR4, or TNFR1 stimulation and ZBP1/DAI-mediated necroptotic cell death after HSV-1 infection. The patient’s fibroblasts displayed no detectable RIPK3 expression. After TNFR1 or TLR3 stimulation, the patient’s cells did not undergo apoptosis or necroptosis. After HSV-1 infection, the cells supported excessive viral growth despite normal induction of antiviral IFN-β and IFN-stimulated genes (ISGs). This phenotype was, nevertheless, rescued by application of exogenous type I IFN. The patient’s human pluripotent stem cell (hPSC)–derived cortical neurons displayed impaired cell death and enhanced viral growth after HSV-1 infection, as did isogenic RIPK3-knockout hPSC-derived cortical neurons. Inherited RIPK3 deficiency therefore confers a predisposition to HSE by impairing the cell death–dependent control of HSV-1 in cortical neurons but not their production of or response to type I IFNs.

Background Cognitive impairment is one of the serious complications in diabetic patients. Iron accumulation is thought to be related to degenerative diseases and diabetes. Microglia have been shown to have features of iron accumulation in Alzheimer 's disease (AD). Triggering receptor expressed on myeloid cells-1(TREM-1)acts as an activating receptor for myeloid cells and is elevated in several neurodegenerative diseases. It is unclear whether microglial iron overload is involved in diabetic associated cognitive impairment (DACI), and whether there is an association between TREM-1 and iron metabolism.Methods We established a model cultured in high glucose (HG) for 72 hours in BV2/HMC3 and another one high fat diet (HFD) combined with STZ in C57 mice. Intracellular mitochondrial changes were observed by Transmission Electron Microscopy, intracellular Fe2 +, GSH/GSSG, MDA and ROS were detected using kits to assess lipid peroxidation in microglia. Prussian blue staining was used to observe iron deposition in the hippocampus. Cognitive performance of mice was assessed by Y-maze and novel object experiments (NOR). Western blot and immunofluorescence were used to observe the expression of iron and antioxidant-related protein (FPN1, FTL, TFR1,GPX4), apoptosis-related protein (BCL-2, BAX and Caspase3), TREM-1, endoplasmic reticulum stress (ERS)-related protein (BIP, P-IRE, IRE, ATF6, P-PERK, PERK, P-eIF2α, eIF2α, ATF4, CHOP).Results We found that hippocampus and microglia undergo iron overload and antioxidant inactivation in HFD/STZ mice. Iron overload, with increase of TREM-1 and antioxidant inactivation, occurred in BV2/HMC3 cultured by HG. Fer-1 could alleviate it by inhibiting HG-induced change of FPN1, GPX4, TFR1, as well as Fe2 +, GSH/GSSG ratio, MDA and ROS. Inhibiting TREM-1 by LP17 could block it, too. Furthermore, PERK/ eIF2α/ATF4/CHOP was obviously down-regulated by LP17 in HG cultured BV2. When LP17 was administered intraperitoneally, cognitive impairment was improved in HFD/STZ mice, iron deposition and antioxidant inactivation in microglia of hippocampus were relieved.Conclusions In this study, we found that iron deposition and antioxidant inactivation occurred in microglia of hippocampus in HFD/STZ mice, accompanied by increase of TREM-1, while inhibition of TREM-1 expression alleviated it and improved cognitive dysfunction, which was partially regulated by PERK/ eIF2α/ATF4/CHOP.

Copper oxide nanoparticles (CuO NPs) have received considerable attention for their toxic effects on crops and potential application in agriculture. In order to investigate the biological effects of CuO NPs on plants, we exposed cucumber (Cucumis sativus) to two sizes of CuO NPs (510 nm, μCuO and 43 nm, nCuO). Results indicated that with concentration increased, the available Cu content in soil increased significantly. The addition of CuO NPs increased Cu content and other nutrient element (e.g., K, P, Mn, and Zn) content in plants. However, diverse particle sizes had different effects. The nCuO treatment had larger translocation factor, higher nutrient element content in fruits, and lower oxidative damage than μCuO treatment. Moreover, nCuO of 100 mg/kg could stimulate cucumber growth, while μCuO had no obvious effects on growth. Conclusively, CuO NPs could be used as copper fertilizer to supply copper to cucumber. The nCuO had better effects on improving the bioavailability of Cu and nutritional value of fruits. These results can help develop strategies for safe disposal of CuO NPs as agricultural fertilizer.

Supplementary Data

Purpose:Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer.Patients and Methods:This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1.Results:A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5–18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6–78.2] and 70.8% (95% CI, 61.5–79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3–13.9) and 10.3 months (95% CI, 9.2–12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2–96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred.Conclusions:Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.

Objectives: To evaluate the predictive significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in the prognosis of high-grade endometrial carcinoma and to establish a novel predictive model. Design: A retrospective multicenter study. Setting: Fifteen hospitals of the Chinese Endometrial Carcinoma Consortium. Population: This study included 910 high-grade epithelial endometrial carcinoma patients from the multicenter who underwent initial surgical treatment between January 1, 2005, and December 31, 2019. Methods: Data was retrospectively obtained from the medical records and follow-up information of patients. Cox proportional hazard regression models were developed to predict the risk of recurrence and death at 3, 5, and 10 years, and the models were validated and calibrated. The area under the curve was used to measure the predictive performance of the model. Main outcomes measures: Disease-free survival and overall survival. Result: Platelet-lymphocyte ratio and neutrophil-lymphocyte ratio were risk factors for recurrence, and neutrophil-lymphocyte ratio was a risk factor for death. We established models for predicting death and recurrence. In the validation cohort, the area under receiver operating characteristic curve of disease-free survival model at 3,5 and 10 years was 0.72, 0.77, 0.77, and of overall survival model was 0.72, 0.81, and 0.84. Kaplan–Meier survival analysis showed a significant difference between low-risk and high-risk groups. Conclusions: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are risk factors affecting the prognosis of high-grade endometrial carcinoma patients. This novel prediction model for high-grade endometrial carcinoma can provide accurate postoperative risk classification and prognosis prediction for patients. Keywords: Endometrial carcinoma, prognostic model, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have been focusing on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we propose a novel mode for cancer metastasis. Here we show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance genes are induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source of the distal tissue tumor metastasis. This conclusion is supported by the presence of fused cells with both macrophage and tumor cell characteristics in the peripheral blood and ascites of patients with ovarian cancer. By suppressing the expression of CD206 in M2 macrophages by siRNA, we show that the growth and metastasis of tumors is suppressed at the in vitro cell line and in the in vivo experimental mice models. In summary, we show that M2 macrophages in the blood circulation undergo a "change of loyalty" to become "cancer cells" that undergo distal tissue metastasis, which can be suppressed by the knockdown of CD206 expression.

Essential oils (EOs) have been proved as natural food preservatives because of their effective and wide-spectrum antimicrobial activity. They have been extensively explored for potential applications in food industry, and substantial progresses have been achieved. However well EOs perform in antibacterial tests in vitro, it has generally been found that a higher level of EOs is needed to achieve the same effect in foods. Nevertheless, this unsimilar effect has not been clearly quantified and elaborated, as well as the underlying mechanisms. This review highlights the influence of intrinsic properties (e.g., oils and fats, carbohydrates, proteins, pH, physical structure, water, and salt) and extrinsic factors (e.g., temperature, bacteria characteristics, and packaging in vacuum/gas/air) of food matrix systems on EOs action. Controversy findings and possible mechanism hypotheses are also systematically discussed. Furthermore, the organoleptic aspects of EOs in foods and promising strategies to address this hurdle are reviewed. Finally, some considerations about the EOs safety are presented, as well as the future trends and research prospects of EOs applications in foods. The present review aims to fill the evidenced gap, providing a comprehensive overview about the influence of the intrinsic and extrinsic factors of food matrix systems to efficiently orientate EOs applications. Both intrinsic properties and extrinsic factors of food matrix affect the EOs action.EOs influence on the food organoleptic aspects were reviewed.Promising strategies for overcoming the organoleptic aspects of EOs were listed.Future research prospects are outlined to accelerate EOs application in foods. Both intrinsic properties and extrinsic factors of food matrix affect the EOs action. EOs influence on the food organoleptic aspects were reviewed. Promising strategies for overcoming the organoleptic aspects of EOs were listed. Future research prospects are outlined to accelerate EOs application in foods.

The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown.This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation.LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P 0.001) and prognostic prediction (P 0.0001) and was selected for further study. The functional role of the prognostic miR-532-5p-correlated competing endogenous RNA (ceRNA) network was investigated to clarify the crosstalk between LDs and LNM. The underlying mechanism was determined using site-directed mutagenesis, dual luciferase reporter assays, RNA immunoprecipitation assays, and rescue experiments. A xenograft LNM model was established to evaluate the effect of miR-532-5p and orlistat combination therapy on tumor growth and LNM.A novel 5-miRNAs prognostic signature was constructed to better predict the prognosis of CC patient. Further study demonstrated that miR-532-5p inhibited epithelial-mesenchymal transition and lymphangiogenesis by regulating LDs accumulation. Interestingly, we also found that LDs accumulation promoted cell metastasis in vitro. Mechanistically, we demonstrated a miR-532-5p-correlated ceRNA network in which LINC01410 was bound directly to miR-532-5p and effectively functioned as miR-532-5p sponge to disinhibit its target gene-fatty acid synthase (Our findings highlight a LD accumulation-dependent mechanism of miR-532-5p-modulated LNM and support treatment with miR-532-5p/orlistat as novel strategy for treating patients with LNM in CC.

Soil cadmium (Cd) and pyrene (PYR) pollutions have gained worldwide attention due to their negative effects on the environment. Intermittent flooding in rain-rich areas may affect phytoremediation of Cd and PYR in soil. Therefore, a pot-culture experiment, with and without flooding, was conducted to study the effects of flooding on soil Cd and PYR phytoremediation. Concentrations of Cd, PYR, and nutrients in soils and plants, as well as plant physiological and biochemical responses, were examined. Under both flooding and non-flooding conditions, willow (Salix × aureo-pendula CL 'J1011') demonstrated a better ability to remove soil Cd and PYR. Flooding led to higher Cd accumulation in roots than that in shoots. Conversely, non-flooding resulted in higher Cd accumulation in shoots than that in roots. The maximum concentrations of Cd in shoots were 11.02 and 14.07 mg kg