[Influencing Factors of Cadmium Content in Wheat Grain: A Meta-analysis and Decision Tree Analysis].

Rapid urbanization, industrialization, and agricultural intensification have resulted in serious soil problems, such as soil acidification and cadmium pollution, affecting food security and human health. Wheat is the second largest food crop in China and has a strong accumulation capacity for cadmium. Understanding the influencing factors of cadmium content in wheat grain is crucial to realize the safe production of wheat. However, a comprehensive and quantitative analysis of how soil physicochemical properties and cultivars affect wheat cadmium accumulation is lacking. The Meta-analysis and decision tree analysis of 56 related studies published in the past 10 years showed that the proportion of cadmium content in soil and wheat grain exceeding the national standard was 52.6% and 64.1%, respectively. Among soil physical and chemical properties, pH, organic matter, available phosphorus, and total soil cadmium content were the important factors affecting the cadmium content in wheat grains. When soil pH ≤ 5.5 and 5.5

OECs Prevented Neuronal Cells from Apoptosis Partially Through Exosome-derived BDNF.

It is known that neurotrophic factors are a major source of the neuroprotective effects of olfactory ensheathing cells (OECs). However, the form of neurotrophic factors that originate from OECs is not fully understood. Our previous study demonstrated that OECs could secrete exosome (OECs-Exo), which provided neuroprotection by switching the phenotype of macrophages/microglia. Considering that exosomes could also be taken up by neurons, we explored the direct effect of OECs-Exo on neuronal survival and the underlying mechanism. Electron microscopy, nano-traffic analysis, and Western blotting were applied to identify the OECs-Exo. The effect of OECs-Exo on neuronal survival was tested by flow cytometry and TUNEL staining. Western blotting and ELISA were used to detect neurotrophic factors in purified OECs-Exo. We first isolated OECs-Exo and found that OECs-Exo exerted protective effects on neuronal survival in response to TNF-α challenge. Brain-derived neurotrophic factor (BDNF) was then identified in OECs-Exo, and its receptor TrkB in neurons was activated by OECs-Exo treatment. Furthermore, we demonstrated that OECs prevented TNF-α-induced apoptosis in neurons partially through exosome-derived BDNF. Our data showed that OECs attenuated TNF-α-induced apoptosis in neurons partially through OEC-Exo-derived BDNF, which might provide a novel strategy for the neuroprotective effect of OEC-Exo-based treatment.

Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling.

Background context: Low back pain, affecting nearly 40% of adults, mainly results from intervertebral disc degeneration (IVDD), while the pathogenesis of IVDD is still not fully elucidated. Recently, some researches have revealed that necroptosis, a programmed necrosis, participated in the progression of IVDD, nevertheless, the underlying mechanism remains unclear. Purpose: To study the mechanism of necroptosis of Nucleus Pulposus (NP) cells in IVDD, focusing on the role of MyD88 signaling. Study design: The expression and co-localization of necroptotic indicators and MyD88 were examined in vivo, and MyD88 inhibitor was applied to determine the role of MyD88 signaling in necroptosis of NP cells in vitro. Methods: Human disc specimens were collected from patients receiving diskectomy for lumbar disc herniation (LDH) or traumatic lumbar fractures after MRI scanning. According to the Pfirrmann grades, they were divided into normal (Grades 1, 2) and degenerated groups (4, 5). Tissue slides were prepared for immunofluorescence to assess the co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 histologically. The combination of TNFα, LPS and Z-VAD-FMK was applied to induce necroptosis of NP cells. Level of ATP, reactive oxygen species (ROS), live-cell staining and electron microscope study were employed to study the role of MyD88 signaling in necroptosis of NP cells. Results: In vivo, the increased expression and co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 were found in NP cells of degenerated disc, while very l low fluorescence intensity in tissue of traumatic lumbar fractures. In vitro, the MyD88 inhibitor effectively rescued the necroptosis of NP cells, accompanied by increased viability, ATP level, and decreased ROS level. The effect of MyD88 inhibition on necroptosis of NP cells was further confirmed by ultrastructure of mitochondria shown by Transmission Electron Microscope (TEM). Conclusion: Our results indicated that the involvement of MyD88 signaling in the necroptosis of NP cells in IVDD, which will replenish the pathogenesis of IVDD and provide a novel potential therapeutic target for IVDD.

TDO2+ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma.

Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ and CD8+ T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2+ myofibroblasts were located distally from tumor nests, and both CD4+ and CD8+ T cells were enriched around them. Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2+ myofibroblasts are potential targets for immunotherapy.

Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals.

Over 100 glycosylphosphatidylinositol-anchored proteins (GPI-APs) are encoded in the mammalian genome. It is not well understood how these proteins are targeted and translocated to the endoplasmic reticulum (ER). Here, we reveal that many GPI-APs, such as CD59, CD55, and CD109, utilize human SND2 (hSND2)-dependent ER targeting machinery. We also found that signal recognition particle receptors seem to cooperate with hSND2 to target GPI-APs to the ER. Both the N-terminal signal sequence and C-terminal GPI attachment signal of GPI-APs contribute to ER targeting via the hSND2-dependent pathway. Particularly, the hydrophobicity of the C-terminal GPI attachment signal acts as the determinant of hSND2 dependency. Our results explain the route and mechanism of the ER targeting of GPI-APs in mammalian cells.

Pyrroloquinoline quinone promotes mitochondrial biogenesis in rotenone-induced Parkinson's disease model via AMPK activation.

Mitochondrial dysfunction is considered to be one of the important pathogenesis in Parkinson's disease (PD). We previously showed that pyrroloquinoline quinone (PQQ) could protect SH-SY5Y cells and dopaminergic neurons from cytotoxicity and prevent mitochondrial dysfunction in rotenone-induced PD models. In the present study we investigated the mechanisms underlying the protective effects of PQQ in a mouse PD model, which was established by intraperitoneal injection of rotenone (3 mg·kg-1·d-1, ip) for 3 weeks. Meanwhile the mice were treated with PQQ (0.8, 4, 20 mg·kg-1·d-1, ip) right after rotenone injection for 3 weeks. We showed that PQQ treatment dose-dependently alleviated the locomotor deficits and nigral dopaminergic neuron loss in PD mice. Furthermore, PQQ treatment significantly diminished the reduction of mitochondria number and their pathological change in the midbrain. PQQ dose-dependently blocked rotenone-caused reduction in the expression of PGC-1α and TFAM, two key activators of mitochondrial gene transcription, in the midbrain. In rotenone-injured human neuroblastoma SH-SY5Y cells, PTMScan Direct analysis revealed that treatment with PQQ (100 µM) differentially regulated protein phosphorylation; the differentially expressed phosphorylated proteins included the signaling pathways related with adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway. We conducted Western blot analysis and confirmed that AMPK was activated by PQQ both in PD mice and in rotenone-injured SH-SY5Y cells. Pretreatment with AMPK inhibitor dorsomorphin (4 µM) significantly attenuated the protective effect and mitochondrial biogenesis by PQQ treatment in rotenone-injured SH-SY5Y cells. Taken together, PQQ promotes mitochondrial biogenesis in rotenone-injured mice and SH-SY5Y cells via activation of AMPK signaling pathway.

A photostable Si-rhodamine-based near-infrared fluorescent probe for monitoring lysosomal pH during heat stroke.

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H+-triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pKa is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects.

Long-term results of CT-guided percutaneous radiofrequency ablation of inoperable patients with stage Ia non-small cell lung cancer: A retrospective cohort study.

BACKGROUND: This study was performed to retrospectively evaluate the 10-year overall survival (OS), progression-free survival (PFS), and local control rates of patients with inoperable stage Ia non-small cell lung cancer (NSCLC) who underwent computed tomography (CT)-guided radiofrequency ablation (RFA) in a single center. MATERIALS AND METHODS: Fifty patients with inoperable NSCLC underwent RFA between 2004 and 2016. Thoracic surgeons evaluated the patients and performed RFA under CT guidance. Follow-up CT and positron emission tomography/CT scans were obtained. Local control rates and recurrence patterns were analyzed. RESULTS: Seventy-three lesions in 50 patients (M:F = 22:28; median age: 73 years; range: 52-82 years) were treated with CT-guided RFA. The mean lesion size was 2.2 cm (range: 1-3 cm). No procedure-related deaths occurred. Low-grade fever was the most common post-ablation complication, with an incidence rate of 36%. The 1-, 2-, 3-, 5-, and 10-year OS rates of patients with Ia NSCLC were 96.0%, 86.5%, 67.1%, 36.3%, and 1%, respectively, and the 1-, 2-, 3-, and 5-year PFS rates were 94.0%, 77.5%, 43.5%, and 10.8%, respectively. The most common pattern of recurrence was local, and 15 patients with recurrence were treated with repeat RFA. Tumor size <2.0 cm was associated with a significantly improved 3-year survival rate of 78.9%. CONCLUSION: CT-guided RFA is feasible and well tolerated by inoperable patients with inoperable stage Ia NSCLC.

Yiqixue buganshen recipe regulates the expression of integrin ανß3 in the endometrium of controlled ovarian hyperstimulation mice.

OBJECTIVE: To observe the effect of Yiqixue Buganshen recipe(, YBR) on the expression of integrin ανß3 in the endometrium of controlled ovarian hyperstimulation mice. METHODS: A total of 180 mice were divided into three groups: model group, treatment group and control group. The treatment and model groups were intraperitoneally injected with gonadotropin-releasing hormone analogue for 7 days; pregnant mare serum gonadotropin was also injected on the 7th day. After 48 h, human chorionic gonadotropin was injected. The control group was injected with an equal volume of saline at the same time. From the start of the experiment, the treatment group was intragastrically administered Jinghouzengzhi Recipe() and Cuhuangti Recipe(). The model group and the control group were intragastrically administered an equal volume of saline. Real-time reverse transcription polymerase chain reaction and Western blotting were used to detect the mRNA and protein expression of integrin ανß3 in mouse endometrium. RESULTS: Integrin ανß3 was expressed in mouse endometrium in all groups. Integrin αßß3 expression increased gradually along with pregnancy, progressing from pregnant day (Pd) 1. Integrin ανß3 expression significantly increased on Pd 4, then began to decrease on Pd 6. Integrin ανß3 expression in the treatment group was higher than in the model group, and the difference was statistically significant (P <0.05). The difference between the treatment group and the control group was not statistically significant (P >0.05). CONCLUSION: YBR improves endometrial receptivity, and may play an important role in embryonic implantation.

Comparative evaluation of surgical stress of laparoscopically assisted vaginal radical hysterectomy and lymphadenectomy and laparotomy for early-stage cervical cancer.

The aim of this study was to objectively evaluate the benefits of laparoscopically assisted vaginal radical hysterectomy and lymphadenectomy for early-stage cervical cancer. Clinical data were prospectively collected from patients with IA-IIB cervical cancer who underwent laparoscopically assisted vaginal radical hysterectomy (n1=33) and laparotomy (n2=30). Peripheral blood samples were obtained prior to surgery and at 1 and 2 h into the operation, as well as on days 1, 4 and 7 following surgery to measure serum interleukin-6, C-reaction protein and cortisol. Results showed that there was no conversion to laparotomy in the laparoscopy group. The average blood loss was 317.23±217.20 ml (laparoscopy group) and 872.58±693.16 ml (laparotomy group). No significant difference was found in the number of resected pelvic lymph nodes (19.74±7.43 in the laparoscopy group and 20.35±6.62 in the laparotomy group). At days 1 and 7 after surgery, the serum IL-6 level was significantly different in the laparoscopy and laparotomy groups (day 1: laparoscopy group 17.14±16.53 pg/ml and laparotomy group 34.32±20.97 pg/ml, p=0.001; day 7: laparoscopy group 6.7±7.21 pg/ml and laparotomy group 17.54±16.47 pg/ml, p=0.001). The serum CRP level was significantly different at days 1 and 7 after the operation (day 1: laparoscopy group 7024.72±949.12 ng/ml and laparotomy group 7586.61±869.42 ng/ml, p=0.018; day 7: laparoscopy group 4357.71±2108.85 ng/ml and laparotomy group 6967.96±995.02 ng/ml, p<0.001). A significant difference was noted in the serum cortisol level at day 4 after the operation (122.29±65.17 ng/ml in the laparoscopy group and 186.76±68.61 ng/ml in the laparotomy group, p<0.001). In conclusion, the differences in clinical data and the various parameters pertinent to surgical stress evaluated in this study suggest that laparoscopic surgery for cervical cancer causes less postoperative stress than conventional open surgery.

[Analysis of circulating DNA level in the plasma of cervical cancer patients].

OBJECTIVE: To determine the plasma DNA level and investigate its clinicopathological significance in women with cervical cancers. METHODS: Blood samples were collected from 42 cervical cancer patients, 20 patients with cervical intraepithelial neoplasia grade III (CINIII) and 20 healthy women. The plasma DNA was extracted using a commercial kit and detected by a fluorescentmeter. RESULTS: The mean plasma DNA level in stage I cervical cancer patients was 12.78-/+5.58 ng/ml, significantly higher than that in CINIII patients (8.10-/+3.06 ng/ml) and normal controls (7.60-/+3.87 ng/ml) (P=0.001). The mean DNA level in stage II-III patients was 17.99-/+7.81 ng/ml, significantly higher than that in stage I patients (P=0.02). No significant difference was found in plasma DNA level between CINIII patients and the normal controls (P>0.05). When the cut-off for diagnosis of cervical cancer was 15.70 ng/ml, the sensitivity, specificity, positive predictive value and negative predictive value were 38.10%, 92.50%, 84.21% and 58.73%, respectively. CONCLUSION: Plasma DNA level is closely related with malignant transformation and development of cervical cancer, and may become a useful means for differential diagnosis of cervical cancer.

Serum leptin levels of menopausal women before and after hormone replacement therapy.

OBJECTIVE: To measure serum leptin levels of menopausal women before and after hormone replacement therapy, and to evaluate the action of hormone replacement therapy in regulating serum leptin levels. METHODS: Serum leptin levels of 27 menopausal women were measured before and after hormone replacement therapy by double-antibody enzyme-linked immunosorbent assay (ELISA) and compared with those measured in 35 women with regular menstrual cycle. RESULTS: Compared with normal control (17.11+/-1.24 ng/ml), menopausal women showed significant higher mean serum leptin levels (20.75+/-2.80 ng/ml, P<0.01). After hormone replacement therapy for 6 months, serum leptin levels in these women declined to (17.46+/-1.71 ng/ml), similar to the leptin levels of normal control (P>0.05). CONCLUSION: Serum leptin levels are significantly higher in menopausal women than in women with regular menstrual cycle, and can be down-regulated by hormone replacement therapy. It is suggested that serum leptin levels might be used as an indicator to evaluate the effect of hormone replacement therapy in menopausal women.