Maize functional requirements drive the selection of rhizobacteria under long-term fertilization practices.

Rhizosphere microbiomes are pivotal for crop fitness, but the principles underlying microbial assembly during root-soil interactions across soils with different nutrient statuses remain elusive. We examined the microbiomes in the rhizosphere and bulk soils of maize plants grown under six long-term (≥ 29 yr) fertilization experiments in three soil types across middle temperate to subtropical zones. The assembly of rhizosphere microbial communities was primarily driven by deterministic processes. Plant selection interacted with soil types and fertilization regimes to shape the structure and function of rhizosphere microbiomes. Predictive functional profiling showed that, to adapt to nutrient-deficient conditions, maize recruited more rhizobacteria involved in nutrient availability from bulk soil, although these functions were performed by different species. Metagenomic analyses confirmed that the number of significantly enriched Kyoto Encyclopedia of Genes and Genomes Orthology functional categories in the rhizosphere microbial community was significantly higher without fertilization than with fertilization. Notably, some key genes involved in carbon, nitrogen, and phosphorus cycling and purine metabolism were dominantly enriched in the rhizosphere soil without fertilizer input. In conclusion, our results show that maize selects microbes at the root-soil interface based on microbial functional traits beneficial to its own performance, rather than selecting particular species.

Commissioning and clinical evaluation of a novel high-resolution quality assurance digital detector array for SRS and SBRT.

PURPOSE: We aimed to perform the commissioning and clinical evaluation of myQA SRS detector array for patient-specific quality assurance (PSQA) of stereotactic radiosurgery (SRS)/ stereotactic body radiotherapy (SBRT) plans. METHODS: To perform the commissioning of myQA SRS, its dose linearity, dose-rate dependence, angular dependence, and field-size dependence were investigated. Ten SBRT plans were selected for clinical evaluation: 1) Common clinical deviations based on the original SBRT plan (Plan0), including multileaf collimator (MLC) positioning deviation and treatment positioning deviation were introduced. 2) Compared the performance of the myQA SRS and a high-resolution EPID dosimetry system in PSQA measurement for the SBRT plans. Evaluation parameters include gamma passing rate (GPR) and distance-to-agreement (DTA) pass rate (DPR). RESULTS: The dose linearity, angle dependence, and field-size dependence of myQA SRS system exhibit excellent performance. The myQA SRS is highly sensitive in the detection of MLC deviations. The GPR of (3%/1 mm) decreases from 90.4% of the original plan to 72.7%/62.9% with an MLC outward/inward deviation of 3 mm. Additionally, when the setup error deviates by 1 mm in the X, Y, and Z directions with the GPR of (3%/1 mm) decreasing by an average of -20.9%, -25.7%, and -24.7%, respectively, and DPR (1 mm) decreasing by an average of -33.7%, -32.9%, and -29.8%. Additionally, the myQA SRS has a slightly higher GPR than EPID for PSQA, However, the difference is not statistically significant with the GPR of (3%/1 mm) of (average 90.4%% vs. 90.1%, p = 0.414). CONCLUSION: Dosimetry characteristics of the myQA SRS device meets the accuracy and sensitivity requirement of PSQA for SRS/SBRT treatment. The dose rate dependence should be adequately calibrated before its application and a more stringent GPR (3%/1 mm) evaluation criterion is suggested when it is used for SRS/SBRT QA.

Comparison of splinting immobilization and K-wire fixation in children with type II phalange neck fracture.

To compare outcomes of type II phalangeal neck fractures in children who received closed reduction followed by splinting immobilization or by K-wire fixation. Furthermore, we analyzed the remodeling potential of residual deformities and the relationship between age and outcomes. Patients in Children's Hospital of Fudan University, Xiamen Hospital were included in the study from October 2015 to October 2018. We compared outcomes between the conservation group and operation group. Remodeling of residual deformities was calculated on a series of anteroposterior and lateral radiography. The correlation between age and outcomes was analyzed using Spearman's rank correlation coefficient. Forty patients (25 males) were enrolled. Nineteen patients had subtype IIa, 19 subtype IIb, and two subtype IIc fractures. Left hands were affected more than right hands, and small finger and proximal phalanx were more frequently involved. There were no significant differences between conservation group and operation group among excellent, good, and fair outcomes. And the outcomes were not significantly different between the IIa and IIb subtypes. An average sagittal remodeling rate was 88.5%, and coronal remodeling rate was 56.71%, respectively, in 13 patients with residual deformities. There was a significant correlation between age and final outcomes. Closed reduction and stable splint fixation may be an effective and economical initial treatment option. Fracture subtype does not seem to be a key factor for choosing treatment options. The fractured phalangeal neck had remodeling potential whether on sagittal or coronal plane. Younger age might be a predictor of better outcomes in children with type II phalanx neck fractures.

Long-term outcomes in lean and non-lean NAFLD patients: a systematic review and meta-analysis.

BACKGROUND: Although nonalcoholic fatty liver disease (NAFLD) commonly occurs in overweight or obese individuals, it is increasingly being identified in the lean population. The association between lean and an increased risk of all-cause mortality among patients with NAFLD remains controversial. We aimed to perform a systematic review and meta-analysis of the literature to evaluate this association and compare the long-term outcomes of lean NAFLD patients and non-lean NAFLD patients. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, and Chinese Biomedical Literature Database (CBM) from inception to October 15, 2021, for relevant original research articles without any language restrictions. Our primary outcome was to compare the all-cause mortality in lean NAFLD patients and non-lean NAFLD patients by qualitative synthesis. Relative risks (RRs) and corresponding 95% confidential intervals (CIs) were pooled with a random effect model. Heterogeneity was evaluated using I-squared (I²) statistics while publication bias was determined using Egger's tests. Subgroup and sensitivity analyses were performed. As for secondary outcomes, we estimated total, cardiovascular, and liver-related mortality, as well as the incidence of diabetes, hypertension, cirrhosis, and cancer in lean and non-lean individuals with NAFLD by quantitative synthesis. Person-years of follow-up were used as the denominator to estimate the mortality and incidence. RESULTS: We identified 12 studies (n = 26,329), 7 of which (n = 7924) were used to evaluate the risk of all-cause mortality between lean and non-lean NAFLD patients. Lean patients with NAFLD were found to be at an elevated risk of death compared to non-lean patients (RR = 1.39, 95% CI 1.08-1.82, heterogeneity: I² = 43%). Among the lean NAFLD population, all-cause mortality was 13.3 (95% CI: 6.7-26.1) per 1000 person-years, 3.6 (95% CI: 1.0-11.7) for liver-related mortality, and 7.7 (95% CI: 6.4-9.2) for cardiovascular-related mortality. The incidence of new-onset diabetes was 13.7 (95% CI 8·2-22.7) per 1000 person-years, new-onset hypertension was 56.1 (95% CI: 40.2-77.9), cirrhosis was 2.3 (95% CI: 1.0-5.0), and cancer was 25.7 (95% CI: 20.3-32.4). CONCLUSIONS: Lean patients with NAFLD had a higher risk of all-cause death than non-lean patients. Body mass index (BMI) should not be used as a criterion to determine whether further observation and therapy of patients with NAFLD are warranted.

Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis.

BACKGROUND: To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients. METHODS: Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05. RESULTS: A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 - 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3-4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%). CONCLUSIONS: Our classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

Galectin-3 is associated with the functional outcome and mortality in stroke patients: A systematic review and meta-analysis.

Introduction: There is still a lack of sensitive predictive tools for stroke outcomes. High galectin-3 concentration is associated with an increased risk of stroke. This study investigated the relationship between blood galectin-3 levels and stroke prognosis. Methods: The PubMed, EMBASE, and Cochrane Library databases were searched as of May 2021. Data from eligible studies on the relationship between galectin-3 and stroke prognosis were extracted for the meta-analysis. Results: The outcomes included the modified Rankin Scale (mRS), mortality rate, and prognostic accuracy of galectin-3 on mRS after stroke. Odds ratio (OR) and 95% CI were used to assess the association between galectin-3 and the prognostic outcomes. Subgroup analysis based on the study design was performed to evaluate the correlation of galectin-3 with mRS and mortality. A random-effects model was adopted for this meta-analysis. A total of 5 studies involving 3607 stroke patients were included. Higher serum galectin-3 level was associated with mRS (OR [95% CI]: 2.02 [1.08, 3.77]) and mortality (OR [95% CI]: 2.17 [1.17, 4.02]) after stroke. Subgroup analysis revealed a similar relationship between galectin-3 and mRS for both prospective and retrospective studies. There were no associations between galectin-3 level and mortality rate in prospective studies. Galectin-3 had a good predictive ability on mRS after stroke (AUC: 0.88, 95% CI:0.85, 0.91). Conclusion: Elevated blood galectin-3 levels were associated with prognostic outcomes after stroke, including functional outcome mRS and mortality rate. Moreover, galectin-3 had a good predictive ability for the prognosis of stroke.

Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Multiomics reveals an essential role of long-distance translocation in regulating plant cadmium resistance and grain accumulation in allohexaploid wheat (Triticum aestivum).

Cadmium (Cd) is a highly toxic heavy metal that readily enters cereals, such as wheat, via the roots and is translocated to the shoots and grains, thereby posing high risks to human health. However, the vast and complex genome of allohexaploid wheat makes it challenging to understand Cd resistance and accumulation. In this study, a Cd-resistant cultivar of wheat, 'ZM1860', and a Cd-sensitive cultivar, 'ZM32', selected from a panel of 442 accessions, exhibited significantly different plant resistance and grain accumulation. We performed an integrated comparative analysis of the morpho-physiological traits, ionomic and phytohormone profiles, genomic variations, transcriptomic landscapes, and gene functionality in order to identify the mechanisms underlying these differences. Under Cd toxicity, 'ZM1860' outperformed 'ZM32', which showed more severe leaf chlorosis, poorer root architecture, higher accumulation of reactive oxygen species, and disordered phytohormone homeostasis. Ionomics showed that 'ZM32' had a higher root-to-shoot translocation coefficient of Cd and accumulated more Cd in the grains than 'ZM1860'. Whole-genome re-sequencing (WGS) and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in abiotic stress responses and ion transport between the two genotypes. Combined ionomics, transcriptomics, and functional gene analysis identified the plasma membrane-localized heavy metal ATPase TaHMA2b-7A as a crucial Cd exporter regulating long-distance Cd translocation in wheat. WGS- and PCR-based analysis of sequence polymorphisms revealed a 25-bp InDel site in the promoter region of TaHMA2b-7A, and this was probably responsible for the differential expression. Our multiomics approach thus enabled the identification of a core transporter involved in long-distance Cd translocation in wheat, and it may provide an elite genetic resource for improving plant Cd resistance and reducing grain Cd accumulation in wheat and other cereal crops.

Impact on xerostomia for nasopharyngeal carcinoma patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study.

PURPOSE: To compare the incidence of xerostomia in nasopharyngeal carcinoma (NPC) patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT) and conventional IMRT (C-IMRT). METHODS: Patients with histologically confirmed NPC who met the eligibility criteria were randomly assigned to receive either SPLS-IMRT or C-IMRT. The primary endpoint was the incidence of xerostomia at 12 months post-IMRT. The secondary endpoints included the xerostomia questionnaire (XQ) score, unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and survival outcomes. RESULTS: Ninety patients were enrolled. Eighty-two patients were included for xerostomia analysis (42 in the SPLS-IMRT group and 40 in the C-IMRT group). At 12 months post-IMRT, the incidence of xerostomia in the SPLS-IMRT group was significantly lower than that in the C-IMRT group (83.4% vs 95.0%; P = 0.007), especially the grade 3 xerostomia (0% vs 12.5%; P < 0.001). The median change in XQ score was similar between the two groups (11.9 points vs 14.1 points; P = 0.194). There was a significantly higher median fractional USFR (0.67 vs 0.35; P = 0.024) and SSFR (0.66 vs 0.32; P = 0.021) in the SPLS-IMRT group than the C-IMRT group. The 3-year LRRFS, DMFS, and OS in the SPLS-IMRT and C-IMRT groups were 92.5% vs 90.9%, 83.8% vs 81.7%, and 88.9% vs 88.2% (all P > 0.05). CONCLUSION: SPLS-IMRT significantly reduced the incidence of xerostomia at 12 months post-IMRT in NPC by recovering parotid gland function earlier than C-IMRT, without compromising survivals. Phase III clinical trials are warranted. (ClinicalTrials.gov, number NCT05020067).

A highly conserved core bacterial microbiota with nitrogen-fixation capacity inhabits the xylem sap in maize plants.

Microbiomes are important for crop performance. However, a deeper knowledge of crop-associated microbial communities is needed to harness beneficial host-microbe interactions. Here, by assessing the assembly and functions of maize microbiomes across soil types, climate zones, and genotypes, we found that the stem xylem selectively recruits highly conserved microbes dominated by Gammaproteobacteria. We showed that the proportion of bacterial taxa carrying the nitrogenase gene (nifH) was larger in stem xylem than in other organs such as root and leaf endosphere. Of the 25 core bacterial taxa identified in xylem sap, several isolated strains were confirmed to be active nitrogen-fixers or to assist with biological nitrogen fixation. On this basis, we established synthetic communities (SynComs) consisting of two core diazotrophs and two helpers. GFP-tagged strains and 15N isotopic dilution method demonstrated that these SynComs do thrive and contribute, through biological nitrogen fixation, 11.8% of the total N accumulated in maize stems. These core taxa in xylem sap represent an untapped resource that can be exploited to increase crop productivity.

Radioprotective effect of X-ray abdominal FLASH irradiation: Adaptation to oxidative damage and inflammatory response may be benefiting factors.

BACKGROUND: Ultrahigh dose-rate irradiation (FLASH-IR) was reported to be efficient in tumor control while reducing normal tissue radiotoxicity. However, the mechanism of such phenomenon is still unclear. Besides, the FLASH experiments using high energy X-ray, the most common modality in clinical radiotherapy, are rarely reported. This study aims to investigate the radiobiological response using 6 MV X-ray FLASH-IR or conventional dose-rate IR (CONV-IR). METHODS: The superconducting linac of Chengdu THz Free Electron Laser (CTFEL) facility was used for FLASH-IR, a diamond radiation detector and a CeBr3 scintillation detector were used to monitor the time structure and dose rate of FLASH pulses. BALB/c nude mice received whole abdominal 6 MV X-ray FLASH-IR or CONV-IR, the prescribed dose was 15 Gy or 10 Gy and the delivered absolute dose was monitored with EBT3 films. The mice were either euthanized 24 h post-IR to evaluate acute tissue responses or followed up for 6 weeks to observe late-stage responses and survival probability. Complete blood count, histological analyses, and measurement of cytokine expression and redox status were performed. RESULTS: The mean dose rate of >150 Gy/s and instantaneous dose rate of >5.5 × 105  Gy/s was reached in FLASH-IR at the center of mice body. After 6 weeks' follow-up of mice that received 15 Gy IR, the FLASH group showed faster body weight recovery and higher survival probability than the CONV group. Histological analysis showed that FLASH-IR induced less acute intestinal damage than CONV-IR. Complete blood count and cytokine concentration measurement found that the inflammatory blood cell counts and pro-inflammatory cytokine concentrations were elevated at the acute stage after both FLASH-IR and CONV-IR. However, FLASH irradiated mice had significantly fewer inflammatory blood cells and diminished pro-inflammatory cytokine at the late stage. Moreover, higher reactive oxygen species (ROS) signal intensities but significantly reduced lipid peroxidation were found in the FLASH group than in the CONV group in the acute stage. CONCLUSIONS: The radioprotective effect of 6 MV X-ray FLASH-IR was observed. The differences in inflammatory responses and redox status between the two groups may be the factors responsible for reduced radiotoxicities following FLASH-IR. Further studies are required to thoroughly evaluate the impact of ROS on FLASH effect.

Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary.

PURPOSE: To evaluate the long-term local control, failure patterns, and toxicities after individualized clinical target volume (CTV) delineation in unilateral nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). METHODS: Unilateral NPC was defined as a nasopharyngeal mass confined to one side of the nasopharynx and did not exceed the midline. From November 2003 to December 2017, 95 patients were retrospectively included. All patients received IMRT. The CTVs were determined based on the distance from the gross tumor. The contralateral para-pharyngeal space and skull base orifices were spared from irradiation. RESULTS: There were three local recurrences and eight regional recurrences in 10 patients during an 84-month follow-up. All local recurrences were within PGTVnx, and all in-field recurrences. No recurrences were found in traditional high-risk areas including contralateral the para-pharyngeal space and skull base orifices. The 10-year local-recurrence-free survival, regional-recurrence-free survival and overall survival were 96.2%, 90.5% and 84.7%, respectively. The dosimetry parameters of the tumor-contralateral organs were all lower than the values of the tumor-ipsilateral side (P < 0.05). The late toxicities occurred mainly in the tumor-ipsilateral organs, including radiation-induced temporal lobe injury, impaired visuality, hearing loss and subcutaneous fibrosis. CONCLUSION: Individualized CTV delineation in unilateral NPC could yield excellent long-term local control with limited out-of-field recurrences, reduced dose to tumor- contralateral organs and mild late toxicities, which is worthy of further exploration.

Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up.

PURPOSE: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. MATERIALS AND METHODS: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. RESULTS: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. CONCLUSION: Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Corrigendum: TRPC1 Inhibits Cell Proliferation/Invasion and Is Predictive of a Better Prognosis of Esophageal Squamous Cell Carcinoma.

[This corrects the article DOI: 10.3389/fonc.2021.627713.].

TRPC1 Inhibits Cell Proliferation/Invasion and Is Predictive of a Better Prognosis of Esophageal Squamous Cell Carcinoma.

BACKGROUND AND OBJECTIVES: In China, over 90% of esophageal cancer (EC) cases are esophageal squamous cell carcinoma (ESCC). ESCC is a frequently malignant tumor with poor prognosis despite the development of comprehensive therapeutic strategies, for which there is still a lack of effective prognostic factors. Previous studies found that the abnormal expression of TRPC1 is closely related to the proliferation, invasion, metastasis, and differentiation of various tumors. However, the relationship between TRPC1 and ESCC is currently unclear. The present study aimed to clarify the clinical significance of TRPC1 and to preliminarily assess the molecular mechanism by which TRPC1 regulates cell proliferation, migration, and invasion in ESCC. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to determine the expression of TRPC1 and Ki-67 in 165 cases of ESCC. The correlations between TRPC1 expression and clinicopathological characteristics were determined, and both univariate and multivariate analyses were utilized to quantify the impact of TRPC1 expression on patient survival. Cell Counting Kit-8, scratch wound healing, and transwell assays were used to determine the effects of TRPC1 on proliferation, migration, and invasion in ESCC in vitro, respectively. RESULTS: The positive expression rate of TRPC1 showed significantly decreased in ESCC (45.50%) compared with the levels in normal esophageal mucosa (NEM; 80.80%) and high-grade intraepithelial neoplasia (HGIEN; 63.20%) (P<0.001). Higher expression rate of TRPC1 was associated with low lymph node metastasis (P<0.001), high differentiation (rs = 0.232, P=0.003), and low Ki-67 (rs = -0.492, P<0.001). We further revealed that low expression of TRPC1 was associated with poor prognosis (Disease-free survival, DFS: 95% CI=0.545-0.845, P=0.001; Overall survival, OS: 95% CI=0.553-0.891, P=0.004). Furthermore, we showed that downregulation of TRPC1 promoted the proliferation, migration, and invasion of human esophageal squamous cell carcinoma cell line EC9706 in vitro. In contrast, overexpression of TRPC1 inhibited the proliferation, migration, and invasion of human esophageal squamous cell carcinoma cell line KYSE150 (P<0.01), in a manner at least in part mediated through the AKT/p27 pathway. CONCLUSION: TRPC1 inhibited the proliferation, migration, and invasion of EC9706 and KYSE150 cells, at least, in part mediated through the AKT/p27 pathway in vitro. The downregulation of TRPC1 may be one of the most important molecular events in the malignant progression of ESCC. TRPC1 could be a new candidate tumor suppressor gene and a new prognostic factor of ESCC.

DVH Prediction for VMAT in NPC with GRU-RNN: An Improved Method by Considering Biological Effects.

PURPOSE: A recurrent neural network (RNN) and its variants such as gated recurrent unit-based RNN (GRU-RNN) were found to be very suitable for dose-volume histogram (DVH) prediction in our previously published work. Using the dosimetric information generated by nonmodulated beams of different orientations, the GRU-RNN model was capable of accurate DVH prediction for nasopharyngeal carcinoma (NPC) treatment planning. On the basis of our previous work, we proposed an improved approach and aimed to further improve the DVH prediction accuracy as well as study the feasibility of applying the proposed method to relatively small-size patient data. METHODS: Eighty NPC volumetric modulated arc therapy (VMAT) plans with local IRB's approval in recent two years were retrospectively and randomly selected in this study. All these original plans were created using the Eclipse treatment planning system (V13.5, Varian Medical Systems, USA) with ≥95% of PGTVnx receiving the prescribed doses of 70 Gy, ≥95% of PGTVnd receiving 66 Gy, and ≥95% of PTV receiving 60 Gy. Among them, fifty plans were used to train the DVH prediction model, and the remaining were used for testing. On the basis of our previously published work, we simplified the 3-layer GRU-RNN model to a single-layer model and further trained every organ at risk (OAR) separately with an OAR-specific equivalent uniform dose- (EUD-) based loss function. RESULTS: The results of linear least squares regression obtained by the new proposed method showed the excellent agreements between the predictions and the original plans with the correlation coefficient r = 0.976 and 0.968 for EUD results and maximum dose results, respectively, and the coefficient r of our previously published method was 0.957 and 0.946, respectively. The Wilcoxon signed-rank test results between the proposed and the previous work showed that the proposed method could significantly improve the EUD prediction accuracy for the brainstem, spinal cord, and temporal lobes with a p value < 0.01. CONCLUSIONS: The accuracy of DVH prediction achieved in different OARs showed the great improvements compared to the previous works, and more importantly, the effectiveness and robustness showed by the simplified GRU-RNN trained from relatively small-size DVH samples, fully demonstrated the feasibility of applying the proposed method to small-size patient data. Excellent agreements in both EUD results and maximum dose results between the predictions and original plans indicated the application prospect in a physically and biologically related (or a mixture of both) model for treatment planning.

Repair function of essential oil from Crocodylus Siamensis (Schneider, 1801) on the burn wound healing via up-regulated growth factor expression and anti-inflammatory effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocodile oil has been used by traditional physicians around the world to treat wound healing and inflammation. However, the scientific rationale and mechanism behind its use in vivo has not been fully researched. AIMS OF THE STUDY: We mainly investigated the mechanism during crocodile oil treatment of up-regulated growth factor expression and anti-inflammatory on burn wound healing in rats. MATERIALS AND METHODS: The moisture and nitric oxide (NO) levels in the skin of rats were analyzed in the first 14 days after burn and the changes of the structure of the skin tissues in the wound healing were studied by hematoxylin-eosin (H.E.) staining within 21 days after scald. The inflammatory factor on burn wound healing in rats was dected by ELISA kits and Q-PCR. the expression of a variety of growth factors (TGF-ß1, VEGE-α, EGF) and PCNA in the skin tissue after burns was evaluated using immunohistochemistry. The down-regulated phosphorylation of p38 MAPK in the wound healing was confirmed by Western-blot analysis. In addition, TEM was used to observe the ultrastructure of scalded skin. RESULTS: This study showed that crocodile oil could significantly reduce the protein and mRNA levels of TNF-α, IL-1ß and IL-6. And it was found that the phosphorylation of p38 MAPK was down-regulated in the wound healing (p < 0.05). Meanwhile, crocodile oil can promote the expression of a variety of growth factors (TGF-ß1, VEGE-α, EGF) and PCNA in the skin tissue after burns, and promote the repair of collagen fibers in the dermis, preventing the production of melanin and maintain the appearance of repaired skin.

Establishment of an immortalized stromal cell line derived from human Endometriotic lesion.

BACKGROUND: Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs). METHODS: The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1ß remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation. CONCLUSION: This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.

RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial-mesenchymal transition and proliferation in endometriosis.

Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive-age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial-mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial-mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up-regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up-regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis.

[Nitrogen content inversion of wheat canopy leaf based on ground spectral reflectance data]. / åŸºäºŽåœ°é¢è§‚æµ‹å ‰è°±æ•°æ®çš„å†¬å°éº¦å† å±‚å¶ç‰‡æ°®å«é‡åæ¼”æ¨¡åž‹.

Canopy nitrogen content in wheat is a key indicator of wheat grain yield and quality. When using remote sensing technology to predict wheat canopy nitrogen content, a hyperspectral mode with high adaptability and high accuracy is needed to improve the inversion efficiency. We developed a new three-band spectral vegetation index (NEW-NDRE) by combining a two-band spectral index NDRE and the spectral reflectance at 550 nm based on field data collected from different sites, years, with different varieties and nitrogen levels and at multiple growth stages. The NEW-NDRE was compared with 11 traditional spectral vegetation indices in terms of wheat canopy nitrogen content inversion. NEW-NDRE and three traditional indices (NDRE, NDDA and RI-1dB) all closely correlated with wheat canopy nitrogen content. NEW-NDRE displayed the highest correlation with wheat canopy nitrogen content at early grain filling stage, with a coefficient (R2) of 0.9 and a root mean squared error (RMSE) of 0.4. The inversion model developed with the NEW-NDRE was validated with an independent dataset. The relative error (RE) of the model was 9.3%, which was significantly lower than that of NDRE, NDDA and RI-1dB. Generally, NEW-NDRE is a more robust index for wheat canopy nitrogen content inversion than traditional indices through eliminating environmental limitation, and it could be used as a new tool for precise fertilizer application.