The Difference of Milk-Derived Extracellular Vesicles from Cow Colostrum and Mature Milk on miRNAs Expression and Protecting Intestinal Epithelial Cells against Lipopolysaccharide Damage.

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1ß). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation.

[Blocking Effects of Foliar Conditioners on Cadmium, Arsenic, and Lead Accumulation in Wheat Grain in Compound-contaminated Farmland].

Heavy metal contamination of soil has become a hot issue of social concern due to its impact on the safety of agricultural products in recent years. Wheat is one of the most dominant staple food crops worldwide and has become a major source of toxic metals in human diets. Foliar application was considered to be a more efficient and economical method of heavy metal remediation. Field experiments were carried out in Cd-, As-, and Pb-contaminated farmland soils. The effects of foliar conditioners on the accumulation of Cd, As, and Pb in wheat grains were investigated after being sprayed with Zn (0.2% ZnSO4), Mg (0.4% MgSO4), and Mn (0.2% MnSO4) separately and in combination. Thus, the effective foliar conditioners were selected to block the accumulation of Cd, As, and Pb in wheat grains grown in combined heavy metal-contaminated farmland in north China. The results showed that, compared with that in the control, the Cd, As, and Pb contents in wheat grains of the Zn+Mg+Mn foliar treatment were significantly decreased by 18.96%, 23.87%, and 51.31%, respectively, and TFgrain/straw decreased by 14.62%, 27.73%, and 47.70%, respectively. Thus, spraying the compound foliar conditioner of Zn+Mg+Mn could effectively reduce heavy metal accumulation in wheat grains through inhibition translocation of those metals from stem leaves to grain. In addition, the results indicated that Cd and As were mainly distributed at the central endosperm (34.08%-37.08%), whereas Pb was primarily distributed at the pericarp and seed coat (27.78%) of the wheat grain. Compared with that in the control, spraying the compound foliar conditioner of Zn+Mg+Mn extremely decreased Cd and As accumulation in the aleurone layer of the wheat grain by 81.10% and 82.24%, respectively. Except for the pericarp, seed coat, and central endosperm layers, the Pb content in each grain layer was dramatically decreased by 42.85% to 91.15%. There was only a significant negative correlation between heavy metal content and Zn content in the aleurone layer (P2) of wheat flour. In summary, the accumulation of Cd, As, and Pb in wheat grains, especially in the aleurone layer, could be effectively reduced by foliar conditioner application at the jointing, booting, and early filling stages of wheat, separately. Furthermore, besides the foliar treatment, removing wheat bran to reduce Cd contamination in wheat grains is highly recommended to ensure the safe production of wheat.

Novel model integrating computed tomography-based image markers with genetic markers for discriminating radiation pneumonitis in patients with unresectable stage III non-small cell lung cancer receiving radiotherapy: a retrospective multi-center radiogenomics study.

BACKGROUND: Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC. METHODS: In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively. RESULTS: The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram. CONCLUSION: Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.

[Distribution and Transport of Cadmium and Arsenic in Different Aboveground Parts of Wheat After Flowering].

To investigate the effects of leaves and stems on the accumulation and transport of cadmium(Cd) and arsenic(As) in wheat shoots after flowering, a field experiment was conducted in a typical Cd and As co-contaminated agricultural land to explore the distribution and translocation of Cd and As in the different parts of two wheat cultivars after flowering. The results showed that Cd was mainly distributed in the nodes of two varieties, and the translocation factors of Cd from internode 3 to node 2, from internode 2 to node 1, and from sheath 1 to node 1 were markedly higher than those of other aboveground parts during the grain-filling stage. However, Cd was mainly distributed in the leaves, and the translocation factors of Cd from sheath to leaf and from node 1 to rachis was significantly higher than those of other parts at the mature stage. In addition, the transport capacity of Cd from glume to rachis and from rachis to grain in JM22 was significantly lower than that in SN28, which significantly reduced Cd concentrations in the rachis, glume, and grain of JM22 by 22.3%, 40.8%, and 44.4%, respectively. Meanwhile, As was mainly distributed in the wheat leaves from the grain-filling stage to the mature stage, and As concentrations in the glume and grain of JM22 were 25.8% and 33.3% lower than those of SN28, respectively. Additionally, the translocation factors of As from the sheath to the node were significantly 438% and 190% higher than that from leaf to sheath and from node to internode during the whole grain filling stage and mature stage. Moreover, the translocation factors of As from glumes to grains and from rachis to grains in JM22 were 40.6% and 44.4% lower than that in SN28, respectively. In summary, flag leaf, node 1, and the rachis had regulated Cd transport and accumulation in wheat grains, whereas leaf 3, flag leaf, node 1, the glumes, and the rachis were mainly responsible for As transport and accumulation in wheat grains.

Influence of Estrus on Dairy Cow Milk Exosomal miRNAs and Their Role in Hormone Secretion by Granulosa Cells.

Estrus is crucial for cow fertility in modern dairy farms, but almost 50% of cows do not show the behavioral signs of estrus due to silent estrus and lack of suitable and high-accuracy methods to detect estrus. MiRNA and exosomes play essential roles in reproductive function and may be developed as novel biomarkers in estrus detection. Thus, we analyzed the miRNA expression patterns in milk exosomes during estrus and the effect of milk exosomes on hormone secretion in cultured bovine granulosa cells in vitro. We found that the number of exosomes and the exosome protein concentration in estrous cow milk were significantly lower than in non-estrous cow milk. Moreover, 133 differentially expressed exosomal miRNAs were identified in estrous cow milk vs. non-estrous cow milk. Functional enrichment analyses indicated that exosomal miRNAs were involved in reproduction and hormone-synthesis-related pathways, such as cholesterol metabolism, FoxO signaling pathway, Hippo signaling pathway, mTOR signaling pathway, steroid hormone biosynthesis, Wnt signaling pathway and GnRH signaling pathway. Consistent with the enrichment signaling pathways, exosomes derived from estrous and non-estrous cow milk both could promote the secretion of estradiol and progesterone in cultured bovine granulosa cells. Furthermore, genes related to hormonal synthesis (CYP19A1, CYP11A1, HSD3B1 and RUNX2) were up-regulated after exosome treatment, while exosomes inhibited the expression of StAR. Moreover, estrous and non-estrous cow-milk-derived exosomes both could increase the expression of bcl2 and decrease the expression of p53, and did not influence the expression of caspase-3. To our knowledge, this is the first study to investigate exosomal miRNA expression patterns during dairy cow estrus and the role of exosomes in hormone secretion by bovine granulosa cells. Our findings provide a theoretical basis for further investigating milk-derived exosomes and exosomal miRNA effects on ovary function and reproduction. Moreover, bovine milk exosomes may have effects on the ovaries of human consumers of pasteurized cow milk. These differential miRNAs might provide candidate biomarkers for the diagnosis of dairy cow estrus and will assist in developing new therapeutic targets for cow infertility.

Recurrence patterns are significantly associated with the 18F­FDG PET/CT radiomic features of patients with locally advanced non­small cell lung cancer treated with chemoradiotherapy.

A model for predicting the recurrence pattern of patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy is of great importance for precision treatment. The present study analyzed whether the comprehensive quantitative values (CVs) of the fluorine-18(18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) radiomic features and metastasis tumor volume (MTV) combined with clinical characteristics could predict the recurrence pattern of patients with LA-NSCLC treated with chemoradiotherapy. Patients with LA-NSCLC treated with chemoradiotherapy were divided into training and validation sets. The recurrence profile of each patient, including locoregional recurrence (LR), distant metastasis (DM) and both LR/DM were recorded. In the training set of patients, the primary tumor prior radiotherapy with 18F-FDG PET/CT and both primary tumors and lymph node metastasis were considered as the regions of interest (ROIs). The CVs of ROIs were calculated using principal component analysis. Additionally, MTVs were obtained from ROIs. The CVs, MTVs and the clinical characteristics of patients were subjected to aforementioned analysis. Furthermore, for the validation set of patients, the CVs and clinical characteristics of patients with LA-NSCLC were also subjected to logistic regression analysis and the area under the curve (AUC) values calculated. A total of 86 patients with LA-NSCLC were included in the analysis, including 59 and 27 patients in the training and validation sets of patients, respectively. The analysis revealed 22 and 12 cases with LR, 24 and 6 cases with DM and 13 and 9 cases with LR/DM in the training and validation sets of patients, respectively. Histological subtype, CV2-5 and CV3-4 were identified as independent variables in the logistic regression analysis (P<0.05). In addition, the AUC values for diagnosing LR, DM and LR/DM were 0.873, 0.711 and 0.826, and 0.675, 0.772 and 0.708 in the training and validation sets of patients, respectively. Overall, the results demonstrated that the spatial and metabolic heterogeneity quantitative values from the primary tumor combined with the histological subtype could predict the recurrence pattern of patients with LA-NSCLC treated with chemoradiotherapy.

Short-term outcomes of reduced-port laparoscopic surgery versus conventional laparoscopic surgery for total gastrectomy: a single-institute experience.

BACKGROUND: The efficacy of reduced-port laparoscopic surgery (RLS) for total gastrectomy remains unclear. This study focused on evaluating the short-term outcomes of RLS compared with conventional laparoscopic surgery (CLS) for total gastrectomy. METHODS: One hundred and ten patients who underwent completed laparoscopic total gastrectomy for gastric cancer between September 2018 and June 2022 were retrospectively collected and classified into two groups (65 CLS and 45 RLS) according to different operation approach. Twenty-four RLS cases underwent single-incision plus two ports laparoscopic surgery (SILS + 2) and twenty-one underwent single-incision plus one port laparoscopic surgery (SILS + 1). Surgical outcomes, pain intensity, cosmetic and postoperative morbidity, and mortality were compared between groups. RESULTS: The overall incidence of postoperative complications was similar between the CLS group and the RLS group (16.9% vs. 8.9%, P = 0.270). It was also comparable in the Clavien-Dindo classification (P = 0.774). However, compared with the CLS group, the RLS group had a significantly shorter total length of incision (5.6 ± 1.0 cm vs. 7.1 ± 0.7 cm, P = 0.000); shorter time to first ambulation (24.9 ± 5.9 h vs. 27.6 ± 5.0 h, P = 0.009), flatus (3.0 ± 0.8 d vs. 3.5 ± 1.0 d, P = 0.022) and oral intake (4.0 ± 1.6 d vs. 6.1 ± 5.1 d, P = 0.011); lower white blood cell count on the third day after the operation (9.8 ± 4.0*109/L vs. 11.6 ± 4.7*109/L, P = 0.037); and lower visual analogue scale score on postoperative days 1 and 3(3.0 ± 0.7 vs. 3.3 ± 0.7, P = 0.044 and 0.6 ± 0.7 vs. 1.6 ± 0.6, P = 0.000 respectively). On the other hand, it didn't find any difference in short-term outcomes between the SILS + 2 group and the SILS + 1 group (P > 0.05). But the proximal resection margin was longer in the SILS + 2 group than in the SILS + 1 group (2.6 ± 0.7 cm vs. 1.5 ± 0.9 cm, P = 0.046) in patients with adenocarcinoma of the esophagogastric junction (AEG). CONCLUSIONS: RLS for total gastrectomy is a feasible and safe technique when performed by an experienced laparoscopic surgeon. Moreover, compared with SILS + 1, SILS + 2 might have some advantages in AEG patients.

High and low dose of luzindole or 4-phenyl-2-propionamidotetralin (4-P-PDOT) reverse bovine granulosa cell response to melatonin.

Background: Communication between oocytes and granulosa cells ultimately dictate follicle development or atresia. Melatonin is also involved in follicle development. This study aimed to investigate the effects of melatonin and its receptor antagonists on hormone secretion, as well as gene expression related to hormone synthesis, TGF-ß superfamily, and follicle development in bovine granulosa cells, and assess the effects of melatonin in the presence of 4-P-PDOT and luzindole. Methods: Bovine ovaries were collected from a local abattoir and follicular fluid (follicle diameter 5-8 mm) was collected for granulosa cell isolation and culture. Granulosa cells and culture medium were collected 48 h after treatment with melatonin at high dose concentrations (10-5 M) and low dose concentrations (10-9 M) in the absence/presence of 4-P-PDOT and luzindole (10-5 M or 10-9 M). Furthermore, the expression level of genes related to hormonal synthesis (CYP11A1, CYP19A1, StAR, and RUNX2), TGF-ß superfamily (BMP6, INHA, INHBA, INHBB, and TGFBR3), and development (EGFR, DNMT1A, and FSHR) were detected in each experimental group by real-time quantitative PCR. In addition, the level of hormones in culture medium were detected using ELISA. Results: Both 10-5 M and 10-9 M melatonin doses promoted the secretion of inhibin A and progesterone without affecting the production of inhibin B and estradiol. In addition, both promoted the gene expression of INHA, StAR, RUNX2, TGFBR3, EGFR, and DNMT1A, and inhibited the expression of BMP6, INHBB, CYP11A1, CYP19A1, and FSHR. When combined with different doses of 4-P-PDOT and luzindole, they exhibited different effects on the secretion of inhibin B, estradiol, inhibin A, and progesterone, and the expression of CYP19A1, RUNX2, BMP6, INHBB, EGFR, and DNMT1A induced by melatonin. Conclusion: High and low dose melatonin receptor antagonists exhibited different effects in regulating hormone secretion and the expression of various genes in response to melatonin. Therefore, concentration effects must be considered when using luzindole or 4-P-PDOT.

Recurrence and Survival Rates of Patients Who Undergo Minimally Invasive Surgery for Endometrial Carcinoma with Different Prognostic Risk Groups.

OBJECTIVE: To compare the recurrence rate and prognosis between minimally invasive surgical (MIS) approach and open surgical approach of endometrial carcinoma (EC) patients with different prognostic risk groups. METHODS: A retrospective analysis of all cases undergoing EC surgery between January 2011 and March 2018 was performed. The patients were grouped according to the management guidelines of EC patients jointly formulated by the ESGO/ESTRO/ESP 2020. Different surgical approaches were compared with regard to tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 665 patients met the inclusion criteria of which 196 patients underwent MIS (29.5%), and 469 patients underwent open surgery (70.5%). In the MIS group, there was a significant higher rate of recurrence (17.3% vs 6.6%, P = 0.000) compared to the open surgery group. The recurrence rate of MIS was 7.7% (P = 0.000) in the medium-high risk group and 8.2% (P = 0.014) in the high-risk group. Multivariate logistic regression analysis showed that the independent factors influencing recurrence included prognostic risk grouping, surgical approach and lymph vascular space invasion (LVSI) positivity (P < 0.05). K-M survival analysis revealed that in the intermediate and high-risk group of EC, MIS patients had a significantly lower DFS than those undergoing open surgery (P < 0.05), but no significant difference was found in OS. CONCLUSIONS: For patients with EC at moderate and high prognostic risk, MIS is associated with poorer DFS compared to open surgery, but OS was similar across prognostic risk groups. The application of MIS in patients with moderate and high-risk EC needs further research and analysis.

Brain metastases from small cell lung cancer and non-small cell lung cancer: comparison of spatial distribution and identification of metastatic risk regions.

PURPOSE: This study aims to investigate the spatial distribution difference of brain metastases (BM) between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and to identify the metastatic risk in brain regions. METHODS: T1-enhanced MR images of 2997 BM from 728 eligible patients with SCLC and NSCLC were retrospectively reviewed by three independent medical institutions in China. All images were spatially normalised according to the Montreal Neurological Institute space, following BM delineation confirmed by three senior radiologists. The brain regions in the normalised images were identified based on the merged Anatomical Automatic Labeling atlas, and all BM locations were mapped onto these brain regions. Two-tailed proportional hypothesis testing was used to compare the BM observed rate with the expected rate based on the region's volume, and metastatic risk regions were finally identified. RESULTS: In SCLC and NSCLC, BM was mainly present in the deep white matter (22.51% and 17.96%, respectively), cerebellar hemisphere (9.84% and 7.46%, respectively) and middle frontal gyrus (6.72% and 7.97%, respectively). The cerebellar hemisphere was a high-risk brain region in the SCLC. The precentral gyrus, middle frontal gyrus, paracentral lobule and cerebellar hemisphere were high-risk BM in the NSCLC. The inferior frontal gyrus and the temporal pole were a low-risk brain region in the SCLC and NSCLC, respectively. CONCLUSION: The spatial BM distribution between SCLC and NSCLC is similar. Several critical brain regions had relatively low BM frequency in both SCLC and NSCLC, where a low-dose radiation distribution can be delivered due to adequate preoperative evaluations.

NNMT-DNMT1 Axis is Essential for Maintaining Cancer Cell Sensitivity to Oxidative Phosphorylation Inhibition.

Lacking a clear understanding of the molecular mechanism determining cancer cell sensitivity to oxidative phosphorylation (OXPHOS) inhibition limits the development of OXPHOS-targeting cancer treatment. Here, cancer cell lines sensitive or resistant to OXPHOS inhibition are identified by screening. OXPHOS inhibition-sensitive cancer cells possess increased OXPHOS activity and silenced nicotinamide N-methyltransferase (NNMT) expression. NNMT expression negatively correlates with OXPHOS inhibition sensitivity and functionally downregulates the intracellular levels of S-adenosyl methionine (SAM). Expression of DNA methyltransferase 1 (DNMT1), a SAM consumer, positively correlates with OXPHOS inhibition sensitivity. NNMT overexpression and DNMT1 inhibition render OXPHOS inhibition-sensitive cancer cells resistant. Importantly, treatments of OXPHOS inhibitors (Gboxin and Berberine) hamper the growth of mouse tumor xenografts by OXPHOS inhibition sensitive but not resistant cancer cells. What's more, the retrospective study of 62 tumor samples from a clinical trial demonstrates that administration of Berberine reduces the tumor recurrence rate of NNMTlow /DNMT1high but not NNMThigh /DNMT1low colorectal adenomas (CRAs). These results thus reveal a critical role of the NNMT-DNMT1 axis in determining cancer cell reliance on mitochondrial OXPHOS and suggest that NNMT and DNMT1 are faithful biomarkers for OXPHOS-targeting cancer therapies.

Comparison of short-term outcomes between single-incision plus one-port laparoscopic surgery and conventional laparoscopic surgery for distal gastric cancer: a randomized controlled trial.

Background: The technical safety and efficacy of single-incision plus one-port laparoscopic surgery (SILS+1) for distal gastric cancer remain unclear. This study was performed to compare the short-term outcomes of patients with distal gastric cancer undergoing SILS+1 versus conventional laparoscopic surgery (CLS). Methods: This randomized controlled trial involved patients with clinical stage cT1b-3N0-2M0 distal gastric cancer. The patients were randomized to the CLS group or SILS+1 group. The surgical and pathologic outcomes, postoperative mortality, and pain intensity were compared between the two groups. Results: From January 2019 to April 2021, 117 patients were enrolled and assigned to either the CLS group (n=59) or SILS+1 group (n=58). The clinical characteristics, including blood loss, tumor diameter, pathologic stage, number of lymph nodes harvested, and postoperative recovery, were similar between the two groups (P>0.05). There were no statistically significant differences in the overall postoperative complication rates between the CLS group and SILS+1 group (10.2% vs. 6.9%, respectively; P=0.743). The Clavien-Dindo classification was also comparable (P=0.435). However, the operating time was significantly longer in the CLS group than SILS+1 group (207.0±41.2 vs. 185.1±40.7 min, respectively; P=0.005), and the total incision length was significantly shorter in the SILS+1 group than CLS group (6.1±0.6 vs. 7.6±0.7 cm, respectively; P=0.000). Moreover, on the third day after surgery, the visual analog scale (VAS) score was significantly higher in the CLS group than SILS+1 group (1.6±0.6 vs. 0.6±0.7, respectively; P=0.000). Conclusions: The results of this study suggest that SILS+1 for distal gastric cancer performed by an experienced surgeon might be a feasible and safe technique with better cosmetic results and less pain in strictly selected patients. Trial Registration: This trial was registered at www.chictr.org.cn (ChiCTR2100051491).

[Characteristics and Health Risk Assessment of Cadmium, Lead, and Arsenic Accumulation in Leafy Vegetables Planted in a Greenhouse].

In recent years, dust pollution has occurred frequently in spring and haze or fog in autumn and winter. The inhalable particulate matters in the atmosphere, especially PM2.5, loaded in heavy metals such as cadmium, lead, and arsenic, are easily taken up by leafy vegetables and accumulate in the edible parts. It is not clear whether the accumulation of heavy metals in the edible parts of leafy vegetables in greenhouses is also affected by atmospheric deposition. Therefore, a field experiment was conducted to explore characteristics and health risk assessment of cadmium, lead, and arsenic accumulation in leafy vegetables planted in a greenhouse using six types of common leafy vegetables (spinach, leaf lettuce, lettuce, pakchoi, Chrysanthemum coronarium, and fennel) in the Beijing-Tianjin-Hebei region. The results showed that C. coronarium, pakchoi, and spinach are the leafy vegetables with a low accumulation of Cd, Pb, and As, respectively. Fennel is the leafy vegetable with a low accumulation of Cd and Pb. In the greenhouse, Pb concentrations in PM2.5 were 42.6 and 8.4 times of Cd and As, respectively. Moreover, PM2.5-Pb contributed on average 36.5% to the edible parts of six kinds of leafy vegetables, which indicated that the Cd, Pb, and As accumulated in leafy vegetables were mainly derived from the soil. Meanwhile, the concentrations of Cd, Pb, and As in the edible parts of vegetables did not exceed the safety limitations of three heavy metals (GB 2762-2017), and Pb accumulation in leafy vegetables does not pose a health risk to humans. However, Cd in the leafy vegetables could threaten the health of adults and children, except for the intake of fennel. Conversely, As in the C. coronarium could threaten the health of adults and children.

Bioimaging of Pb by LA-ICP-MS and Pb isotopic compositions reveal distributions and origins of Pb in wheat grain.

Atmospheric heavy metal deposition in agroecosystems has increased recently, especially in northern China, which poses serious risks to crop safety and human health via food chain. Wheat grains can accumulate high levels of Pb even when wheat is planted in soils with low levels of Pb. However, the influence of atmospheric deposition on the accumulation and distribution of Pb in wheat grain is still unclear. A field survey was conducted in three districts (A: a district with industrial and traffic pollution; B: a district with traffic pollution; and C: an unpolluted district) in Hebei Province, North China. The grain of wheat cultivated in district A accumulated more Pb from soil and atmospheric deposition than those in other districts, and the bran from district A contained 3.50 and 2.04 times more Pb than those from districts B and C, respectively. The Pb distribution pattern in wheat grain detected by laser ablation inductively coupled mass spectrometry (LA-ICP-MS) was characterized by accumulation mostly in the pericarp and seed coat rather than in the crease, embryo and endosperm. Furthermore, Pb isotopic data showed that airborne Pb was the major source (>50%) of Pb in wheat grain. Interestingly, average contributions of Pb from atmospheric deposition to white flour (78.22%) were higher than its contributions to bran (56.27%). In addition, wheat flag leaves were exposed to PbSO4 at the booting stage, and much greater Pb accumulation (0.33-0.48 mg/kg) was observed in exposed wheat grain than in the control (P < 0.05), PbSO4 constituted most (82.80-100%) of the Pb in the wheat grain. In summary, the results confirmed the efficient foliar Pb uptake and transfer from atmospheric deposition into wheat grain. It would be a new sight for understanding the contribution of airborne Pb to Pb accumulation in wheat grains.

Technical solutions for minimizing wheat grain cadmium: A field study in North China.

The minimization of Cd pollution in wheat is urgently needed in many parts of the world. Thus, the aims of the present study were to evaluate the feasibility of popular technologies (i.e., soil amendment and low-Cd wheat cultivar) at sites with different Cd risk levels (high and low) and to propose a risk-based strategy for safe grain production. At a high-Cd site, wheat variety JM22 yielded significantly lower grain Cd than SX828, regardless of soil amendment (biochar, sepiolite, and microbial agent YZ1). Neither biochar nor sepiolite amendment reduced grain Cd, DTPA-Cd, or bioconcentration factors, possibly due to low dosage. Metagenomic sequencing and quantitative PCR showed that YZ1 colonization had little effect on rhizospheric fungal community structure and could not be sustained through winter. At a low-Cd site, significantly lower grain Cd was observed in JM22, LX99, and JM262, which could be used as low-Cd cultivars in the study area. Interestingly, the grain Cd of JM22 was linearly correlated with soil Cd (R2 = 0.84), which allowed the inference of a soil Cd threshold of 1.55 mg·kg-1, below which JM22 alone was capable of producing safe grain. Cost-benefit analysis also indicated that the use of low-Cd cultivars is promising for pollution control. This study provides viable technical solutions for minimizing the grain Cd of wheat grown in northern China.

[Uptake and Accumulation of Cadmium and Zinc by Two Energy Grasses: A Field Experiment].

The remediation potential of large biomass energy grasses in cadmium-contaminated soil remains ambiguous. A field experiment was carried out in a cadmium-contaminated farmland using two energy grasses and two control plants. The two energy grasses were hybrid pennisetum (Pennisetum americanum×P. purpureum, PAP) and purple elephant grass (P. purpureum 'Purple', PPP), and the two control plants were Iris lactea var. chinensis (ILC) and a cadmium hyperaccumulator, Noccaea caerulescens (NC). The results showed that the aboveground biomass of PAP was the largest among the four plants, and 126 and 36 times that of NC and ILC, respectively, but no significant difference with that of PPP. The concentrations of cadmium and zinc in the shoots and roots of NC were significantly higher than in the other plants. Zinc concentrations in the shoots and roots of ILC were lower than in the other plants, while cadmium concentrations were significantly higher than in PAP and PPP (P<0.05). The amounts of cadmium and zinc accumulated in the shoots of PPP were the highest among the four plants, while cadmium concentrations in the shoots and roots of PPP were significantly lower than in ILC and NC (P<0.05). Cadmium amounts accumulated in PPP shoots were 7.0 and 4.1 times that of ILC and NC, respectively. Zinc amounts accumulated in PPP shoots were 41 and 11 times that of ILC and NC, respectively (P<0.05). Cadmium accumulation in the shoots of PAP was 19.4% lower than in PPP, and zinc accumulation had no significant difference with that of PPP. NC, having a bioconcentration factor of shoot (BCFS) and a translocation factor (TF) for cadmium and zinc both larger than 1, is usable for phytoextraction of soils contaminated by cadmium and zinc. ILC, having a bioconcentration factor of root (BCFR) larger than 1 and a TF lower than 1 for cadmium, is usable for the phytostabilization of soils contaminated by cadmium. PPP, having a BCFR larger than 1 and a TF lower than 1 for zinc, can be used in the phytostabilization of soils contaminated by zinc. Under field conditions, PPP and PAP showed great potential for the extraction and removal of cadmium and zinc from soil due to their large biomass and ability to produce economic benefits, have good application prospects.

Predicting postoperative peritoneal metastasis in gastric cancer with serosal invasion using a collagen nomogram.

Accurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.

Dux-Mediated Corrections of Aberrant H3K9ac during 2-Cell Genome Activation Optimize Efficiency of Somatic Cell Nuclear Transfer.

Differentiated somatic cells can be reprogrammed to totipotent embryos through somatic cell nuclear transfer (SCNT) with low efficiency. The histone deacetylase inhibitor trichostatin A (TSA) has been found to improve SCNT efficiency, but the underlying mechanism remains undetermined. Here, we examined genome-wide H3K9ac during SCNT embryo development and found that aberrant H3K9ac regions resulted in reduced 2-cell genome activation. TSA treatment largely corrects aberrant acetylation in SCNT embryos with an efficiency that is dictated by the native epigenetic environment. We further identified that the overexpression of Dux greatly improves SCNT efficiency by correcting the aberrant H3K9ac signal at its target sites, ensuring appropriate 2-cell genome activation. Intriguingly, the improvement in development mediated by TSA and Kdm4b is impeded by Dux knockout in SCNT embryos. Together, our study reveals that reprogramming of H3K9ac is important for optimal SCNT efficiency and identifies Dux as a crucial transcription factor in this process.

Whole Brain Radiation Therapy Plus Focal Radiation Boost May Generate Better Survival Benefit for Brain Metastases From Non-small Cell Lung Cancer.

BACKGROUND: Owing to improved systemic therapies, the survival of patients with non-small cell lung cancer (NSCLC) was prolonged, and the risk of brain metastases was consequently increased. This study aims to compare different radiotherapy for brain metastases in patients with NSCLC. MATERIALS AND METHODS: The patients with NSCLC who were treated with whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for brain metastases at three medical centers between January 2012 and December 2017 were retrospectively analyzed. RESULTS: Of the 684 eligible patients, 217 received WBRT plus focal radiation boost (WBRT+boost), 324 received WBRT, and 143 received SRS. Patients with WBRT+boost lived longer than those with WBRT (median overall survival (OS), 22.2 vs 13.7 months, P < 0.001) or SRS (22.2 vs 17.3 months, P = 0.011). In subgroup analyses, the survival advantage of WBRT+boost was more obvious among patients with 1 to 3 brain metastases or who received targeted therapy than did SRS. From pair-wise comparisons of intracranial progression-free survival (iPFS), WBRT+boost was also superior to WBRT (12.9 vs 10.6 months, P = 0.028) and SRS (12.9 vs 9.1 months, P = 0.001). CONCLUSIONS: Patients who were treated with WBRT+boost experienced significantly longer OS and iPFS than those with WBRT or SRS alone. WBRT+boost should be a preferred strategy for brain metastases in NSCLC patients.

[Characteristics of Cd, As, and Pb in Soil and Wheat Grains and Health Risk Assessment of Grain-Cd/As/Pb on the Field Scale].

In recent years, heavy metal pollution in farmlands has become increasingly serious because of human activities such as metal smelting, sewage irrigation, and road traffic in China. A field survey was conducted to investigate characteristics of Cd, As, and Pb in soil and wheat grains and assess the health risk of grain-Cd/As/Pb to humans on the fields scale. The farmland was influenced by smelter and sewage irrigation in the attitude and by road traffic in the horizon. The results showed that in farmland soil with moderate pollution levels, Cd, As, and Pb concentrations in soil samples all exceeded the risk screening values of farmland soil (GB 15618-2018), and the exceeding rates were 100%, 100%, and 36.7% respectively; the exceeding rates of Cd and Pb concentrations in wheat grains were 76.7% and 13.3%, respectively (GB 2762-2017). Distance from smelter, river of sewage irrigation, and road had no significant effect on Cd, As, and Pb concentrations in soil but had a significant effect on Cd and As concentrations in wheat grains, with the median Cd and As concentrations of the closest group being 14.9% and 41.8%, respectively, higher than the highest group (P<0.05). The Pb concentrations in soil and wheat grains were influenced by road traffic; the median Pb concentrations of the closest group were 78.9% and 471%, respectively, higher than the highest group (P<0.05). Cd and As in wheat grains have carcinogenic risks (Ri>1×10-4), RCd > RAs, Rchildren > Radult, while Pb poses no health risks in this farmland.