A Preliminary Study of Adjunctive Nonconvulsive Electrotherapy for Treatment-Refractory Depression.

Nonconvulsive electrotherapy (NET) defined as electrical brain stimulation administered like standard electroconvulsive therapy (ECT), but below seizure threshold, could be effective for patients with treatment-refractory depression (TRD) with fewer adverse neurocognitive outcomes. However, there is a lack of studies in Chinese patients with TRD. Thus, this study was conducted to examine the efficacy and safety of adjunctive NET for Chinese patients with TRD. Twenty TRD patients were enrolled and underwent six NET treatments. Depressive symptoms, response, and remission were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 1, 3, and 6 NET treatments. Neurocognitive function was assessed by the Wisconsin Card Sorting Test (WCST) at baseline and after the completion of six NET treatments. Mean HAMD-17 scores declined significantly from 26.2 to 10.4 (p < 0.001) after post-NET. The rates of response and remission were 60.0% (95% CI: 36.5-83.5) and 10.0% (95% CI: 0-24.4), respectively. Neurocognitive performance improved following a course of NET. No significant association was found between changes in depressive symptoms and baseline neurocognitive function. Adjunctive NET appeared to be effective for patients with TRD, without adverse neurocognitive effects. Randomized controlled studies were warranted to confirm these findings.

Prescription practices in the treatment of agitation in newly hospitalized Chinese schizophrenia patients: data from a non-interventional naturalistic study.

BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.

Surgical treatment for shepherd's crook deformity in fibrous dysplasia: THERE IS NO BEST, ONLY BETTER.

BACKGROUND: The optimal strategy for shepherd's crook deformity correction remains technically challenging. In particular, it is difficult to perform an accurate osteotomy based on the pre-operative correction plan. Moreover, the choice of ideal hardware remains unclear. In addition, when combined with the deformity of knee joint, the sequence of deformity correction is another overlooked factor when making a correction strategy. METHODS: From February 2012 to March 2014, we retrospectively examined a cases series in our department involving the creation of three-dimensional (3D) printing osteotomy templates and inner fixation for shepherd's crook deformity in fibrous dysplasia. RESULTS: A total of ten patients of shepherd's crook deformity were enrolled in this study. The neck shaft angle was corrected from a mean value of 88.1° (range, 73-105°) pre-operatively to a mean value of 128.5° (range, 120-135°) post-operatively; no marked loss in the value was observed (mean, 123.7°; range, 115-130°) at the final follow-up. In addition, compared with patients using dynamic hip screw (DHS), longer operation time and additional blood loss were recorded in patients using intramedullary nail (IN). Moreover, after correction of shepherd's crook deformity, two patients were observed more predominant on their pre-existing valgus knee deformity. CONCLUSIONS: 3D printing osteotomy templates facilitate the correction of shepherd's crook deformity. Dynamic hip screw (DHS), combined with polymethylmethacrylate (PMMA) augmentation, yields excellent outcomes and ensures easy placement and non-intramedullary manipulation, lower bleeding volume, and reduced operation time. Prior to the correction of shepherd's crook deformity, the mechanical axis of the lower limb should be carefully examined, and any evidence of valgus knee deformity should be addressed in advance.

MiR-96 regulates bone metabolism by targeting osterix.

MicroRNAs (miRNAs) play important roles in bone metabolism and aging. Here we show that miR-96 was markedly up-regulated in serum of elderly patients with osteoporosis by miRNA microarray analysis and qRT-PCR. Moreover miR-96 was also up-regulated in bone marrow mesenchymal stem cells (BMSCs) of aged humans and mice. Our results show that the over-expression of miR-96 reduced osteogenic differentiation of BMSCs, whereas the inhibition of miR-96 increased osteogenic differentiation of BMSCs. At the molecular level, miR-96 regulated osteogenesis by targeting osterix. Interestingly, over-expression of miR-96 in young mice by intravenous injection of agomiR-96 developed a low bone mass due to impaired osteogenesis. However, inhibition of miR-96 in aged mice attenuated the age-related bone loss. Thus, our data suggest that miR-96 regulates osteogenesis and may represent a potential diagnostic marker or therapeutic target for age-related bone loss.

Is double-approach surgery and tenodesis without a gastrocnemius flap better for dealing with proximal fibular osteosarcoma?

BACKGROUND: Resection of proximal fibular osteosarcoma involving the posteromedial aspect of the fibula is challenging. Reconstruction using a gastrocnemius flap may result in significant lateral instability and abnormal knee movement. Furthermore, postoperative gait may be disturbed by foot drop resulting from scarification of the common peroneal nerve. METHODS: Between January 2011 and December 2013, five patients with proximal fibular osteosarcoma were treated via the double-approach procedure using en bloc resection without a gastrocnemius flap. Simultaneously, all patients received one-stage tenodesis of the anterior tibial and toe extensor tendons. Clinical outcomes, including local tumor recurrence, complications, and functional outcomes, were evaluated. RESULTS: The mean follow-up duration was 47.2 months (range 42-52 months). No patients experienced local recurrence. The patients' Enneking functional scores were excellent (80%) or good (20%) at the final follow-up. CONCLUSIONS: In patients with proximal fibular osteosarcoma, the double-approach procedure allows easier and safer en bloc tumor resection with vessel and nerve protection. One-stage tenodesis without a gastrocnemius flap is associated with good functional outcomes.

The Influence of Abdominal and Ectopic Fat Accumulation on Carotid Intima-Media Thickness: A Chongqing Study.

BACKGROUND: To investigate the effects of abdominal obesity (AO) and nonalcoholic fatty liver disease (NAFLD) with or without AO on carotid arteries by determining carotid intima-media thickness (CIMT). METHODS: A total of 2745 Chinese Han adults (aged between 40 and 50 years old) were recruited and divided into 4 groups: (1) NW-no NAFL group: the normal body weight without NAFLD (n = 1888); (2) AO-no NAFL group: AO without NAFLD (n = 259); (3) NW-with NAFL group: NAFLD without AO (n = 93); and (4) AO-with NAFL group: AO with NAFLD (n = 505). The CIMT rate of each group was compared among 4 groups and the regression analysis was further used to correct confounders. RESULTS: We found that the NW-with NAFL group had a significantly higher CIMT rate than the AO-no NAFL group ([.87 ± .31] versus [.72 ± .29] P < .01) and the AO-with NAFL group ([.87 ± .31] versus [.79 ± .26], P < .01). CONCLUSIONS: The ectopic liver fat accumulation may increase the risk of atherosclerosis. Therefore, screening NAFLD in the population with normal weight may be beneficial for the prevention of atherosclerosis at an early stage.

GDF8 inhibits bone formation and promotes bone resorption in mice.

Growth Differentiation Factor 8 (GDF8), also called myostatin, is a member of the transforming growth factor (TGF)-ß super-family. As a negative regulator of skeletal muscle growth, GDF8 is also associated with bone metabolism. However, the function of GDF8 in bone metabolism is not fully understood. Our study aimed to investigate the role of GDF8 in bone metabolism, both in vitro and in vivo. Our results showed that GDF8 had a negative regulatory effect on primary mouse osteoblasts, and promoted receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro. Intraperitoneal injection of recombinant GDF8 repressed bone formation and accelerated bone resorption in mice. Furthermore, treatment of aged mice with a GDF8 neutralizing antibody stimulated new bone formation and prevented bone resorption. Thus, our study showed that GDF8 plays a significant regulatory role in bone formation and bone resorption, thus providing a potential therapeutic pathway for osteoporosis.

Fabrication of mesoporous lignin-based biosorbent from rice straw and its application for heavy-metal-ion removal.

Lignocellulosic biomass offers the most abundant renewable resource in replacing traditional fossil resources. However, it is still a major challenge to directly convert the lignin component into value-added materials. The availability of plentiful hydroxyl groups in lignin macromolecules and its unique three-dimensional structure make it an ideal precursor for mesoporous biosorbents. In this work, we reported an environmentally friendly and economically feasible method for the fabrication of mesoporous lignin-based biosorbent (MLBB) from lignocellulosic biomass through a SO3 micro-thermal-explosion process, as a byproduct of microcrystalline cellulose. BET analysis reveal the average pore-size distribution of 5.50nm, the average pore value of 0.35cm3/g, and the specific surface area of 186m2/g. The physicochemical properties of MLBB were studied by fourier transform infrared spectroscopy (FTIR), attenuated-total-reflection fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and element analysis. These results showed that there are large amounts of sulfonic functional groups existing on the surface of this biosorbent. Pb(II) was used as a model heavy-metal-ion to demonstrate the technical feasibility for heavy-metal-ion removal. Considering that lignocellulosic biomass is a naturally abundant and renewable resource and SO3 micro-thermal-explosion is a proven technique, this biosorbent can be easily produced at large scale and become a sustainable and reliable resource for wastewater treatment.

Demographic and Clinical Profile of Patients With Dementia Receiving Electroconvulsive Therapy: A Case-Control Study.

PURPOSE: Little is known about the clinical characteristics of patients with dementia receiving electroconvulsive therapy (ECT) for the treatment of behavioral symptoms. This study examined the demographic and clinical profile of patients with dementia receiving ECT in China. METHODS: This was a retrospective, case-control study. The sample was composed of 23 patients with dementia treated with ECT and 71 sex- and age-matched controls treated for a period of 8 years (2007-2014) at the National Clinical Research Centre of Mental Disorders, China. Sociodemographic and clinical data were collected from the electronic chart management system. RESULTS: Multiple logistic regression analysis revealed that ECT was independently associated with high risk for suicide at admission. The recorded indications for ECT included both high risk for suicide and aggressive behavior. Most patients responded to ECT satisfactorily (56.5%) or partially (34.8%) with only mild-moderate transient memory impairment (30.4%). CONCLUSIONS: Although this is a preliminary study limited by the retrospective design and small sample size, findings suggest that ECT is an effective and safe therapeutic intervention to reduce the risk for suicide and aggressive behavior in dementia.

Diabetes mellitus is associated with early chronic venous disorder of the lower extremities in Chinese patients with cardiometabolic risk factors.

BACKGROUND: Metabolic syndrome has received great attention because it poses a potential cardiovascular hazard, which increases the risk of lower extremity atherosclerosis. However, the relationship between the components of metabolic syndrome and the onset of chronic venous disorder of the lower extremities remains unexplained. METHODS: This study investigated the characteristics of cardiometabolic risk factors of early chronic venous disorder of the lower extremities in subjects with cardiometabolic risk. The characteristics of risk factors and diabetes-related complications in diabetic patients with early chronic venous disorder of the lower extremities were also investigated. In addition, the association between early chronic venous disorder and atherosclerosis of the lower extremities was analysed. The study examined 782 subjects with cardiometabolic risk factors, including obesity, hypertension, diabetes mellitus and dyslipidaemia. Lower extremity venous function was measured by digital photoplethysmography. RESULTS: Women had a higher prevalence of early chronic venous disorder than did men (p < 0.01). Male subjects with early chronic venous disorder had a higher systolic blood pressure than those with normal venous function (p < 0.01), and female subjects with early chronic venous disorder had a higher fasting plasma glucose level than did controls (p < 0.05). The prevalence of diabetes mellitus is also significantly higher in female patients with early chronic venous disorder (p = 0.000). Diabetic patients with early chronic venous disorder not only had higher fasting plasma glucose and total cholesterol levels but also had more serious macrovascular complications than the control group. The independent risk factors of early chronic venous disorder in female subjects with cardiometabolic risks were age and fasting plasma glucose in men it was only age Women face a two times greater risk than men. The independent risk factors of early chronic venous disorder in diabetic patients were age, gender, HbA1c and triglyceride levels Women had an almost 12 times greater risk of early chronic venous disorder than men. Among the diabetic patients, the prevalence of early chronic venous disorder did not differ by ankle-brachial index. CONCLUSION: Female subjects with cardiometabolic risk factors or female diabetic patients face a greater risk of early chronic venous disorder than do male subjects. Diabetic patients with early chronic venous disorder had more serious macrovascular complications than did the controls, and the early venous function was found to be correlated with the blood glucose level and triglyceride status.

Bioinformatic analysis of biological changes involved in pelvic organ prolapse.

The molecular mechanisms involved in the pathogenesis of pelvic organ prolapse (POP) remain unclear. This study aimed to identify key molecules involved in the pathogenesis and progression of POP. Differentially expressed genes (DEGs) were identified based on gene expression data extracted from the GSE53868, GSE28660, and GSE12852 datasets in the gene expression omnibus database. The R software was used for data mining, and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to explore the biological functions of DEGs. A protein-protein interaction network (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes database, and hub genes were identified by the Cytoscape plug-in cytoHubba. In addition, the CIBERSORT algorithm was used to analyze and evaluate immune cell infiltration in POP tissues. A total of 92 upregulated DEGs were identified and subjected to enrichment analysis. Gene ontology analysis revealed that these DEGs were associated with response to hormones, positive regulation of cell death, collagen-containing extracellular matrix, and extracellular matrix. Kyoto encyclopedia of genes and genomes pathway analysis showed that the upregulated genes were mainly enriched in the phosphatidylinositol 3-kinase-AKT signaling pathway. The PPI network was structured. Nodes in the PPI network were associated with structural molecular activity and collagen-containing extracellular matrix. A total of 10 hub genes were identified, namely, CDKN1A, IL-6, PPARG, ADAMTS4, ADIPOQ, AREG, activating transcription factor 3, CCL2, CD36, and Cell death-inducing DNA fragmentation factor-like effector A. Furthermore, patients with POP were found to have a higher abundance of CD8-positive T cells in the 3 gene expression omnibus datasets. The abundance of CD8-positive T cells was negatively correlated with that of follicular helper T cells (Pearson correlation coefficient = -0.34, P < .01) or gamma delta T cells (Pearson correlation coefficient = -0.33, P < .01). But was positively correlated with that of M2 macrophages (Pearson correlation coefficient = 0.35, P < .01) and activated memory CD4 T cells (Pearson correlation coefficient = 0.34, P < .01). Altogether, PPARG, ADAMTS4, ADIPOQ, AREG, CD36, and Cell death-inducing DNA fragmentation factor-like effector A genes were discovered in the POP process for the first time, which should be intensively investigated.

Mechanisms of conservation tillage on nitrogen-fertilizer reduction and maize grain improvement in Mollisols of Northeast China: Insights from a 15N tracing study.

Conservation tillage is an important management practice to guarantee soil fertility in degraded Mollisols. It is still unclear, however, whether the improvement and stability of crop yield under conservation tillage can be sustainable with increasing soil fertility and reducing fertilizer-N application. Based on a long-term tillage experiment initiated in Lishu Conservation Tillage Research and Development Station by Chinese Academy of Sciences, we conducted a 15N tracing field micro-plot experiment to investigate the effects of reducing nitrogen application on maize yield and fertilizer-N transformation under long-term conservation tillage agroecosystem. There were four treatments, including conventional ridge tillage (RT), no-tillage with 0% (NT0), 100% (NTS) maize straw mul-ching, and 20% reduced fertilizer-N plus 100% maize stover mulching (RNTS). The results showed that after a complete cultivation round, the average percentages of fertilizer N recovery in soil residues, crop usage, and gaseous loss were 34%, 50%, and 16%, respectively. Compared with conventional ridge tillage, no-tillage with maize straw mulching (NTS and RNTS) significantly increased the use efficiency of fertilizer N in current season by 10% to 14%. From the perspective of N sourcing analysis, the average percentage of fertilizer N absorbed by crop parts (including seeds, straws, roots, and cobs) to the total N uptake reached nearly 40%, indicating that soil N pool was the main source of N for crop uptakes. In comparison with conventional ridge tillage, conservation tillage significantly increased total N storage in 0-40 cm by reducing soil disturbance and increasing organic inputs, and thus ensured the expansion and efficiency increment of soil N pool in degraded Mollisols. Compared with conventional ridge tillage, NTS and RNTS treatments significantly increased the maize yield from 2016 to 2018. In all, by improving fertilizer nitrogen utilization efficiency and maintaining the continuous supply of soil nitrogen, long-term management of no-tillage with maize straw mulching could achieve a stable and increasing maize yield in three consecutive growing seasons and simultaneously reduce environmental risks derived by fertilizer-N losses, even under the condition of 20% reduction of fertilizer-N application, and thus actualize the sustainable development of agriculture in Mollisols of Northeast China.

Effects of no-tillage and different stover mulching amounts on soil microbial community and microbial residue in the Mollisols of China.

To investigate the effects of no-tillage and different amounts of stover mulch on soil microbial community composition and their residues, we set up a field experiment of different amounts of stover mulch under no-tillage on the long-term maize conservation tillage station located in the Mollisols area of Northeast China (built in 2007), including without stover mulch (NT0), 1/3 stover mulch (NT1/3), 2/3 stover mulch (NT2/3) and full stover mulch (NT3/3), and the conservation tillage (plowing without stover mulch, CT) as control. We analyzed phospholipid fatty acid, amino sugar biomarker and soil physicochemical properties at different soil layers (0-5 cm, 5-10 cm, 10-20 cm). The results showed that compared to CT, no-tillage without stover mulch (NT0) did not affect soil organic carbon (SOC), total nitrogen (TN), dissolved organic carbon and nitrogen (DOC, DON), water content, microbial community and their residue. The main effects of no-tillage and stover mulch were found in the topsoil. Specifically, the NT1/3, NT2/3 and NT3/3 significantly increased SOC content by 27.2%, 34.1% and 35.6%, respectively, phospholipid fatty acid content was significantly increased under NT2/3 and NT3/3 by 39.2% and 65.0%, respectively, and NT3/3 significantly increased the content of microbial residue-amino sugar by 47.2% in the depth of 0-5 cm compared with CT. The variations in soil properties and microbial community induced by no-tillage and different amounts stover mulch decreased with soil depth, with almost no difference in the 5-20 cm soil layer. SOC, TN, DOC, DON, and water content were the main factors influencing the composition of the microbial community and the accumulation of microbial residue. Microbial biomass was positively correlated with microbial residue, particularly fungal residue. In conclusion, all stover mulch treatments promoted SOC accumulation to different degrees. When there is sufficient stover, it is advisable to opt for no-tillage with full stover mulch, as it is most conducive to the increases of soil microbial biomass, microbial residue and SOC. In case when the amount of stover is inadequate, however, no-tillage with 2/3 stover mulch can still improve soil microbial biomass and SOC content. This study would provide practical guidance for stover management in conservation tillage and sustainable agricultural development in the Mollisols area of Northeast China.

[Effects of long-term no-tillage and stover mulching on maize yield and its stability.] / é•¿æœŸå è€•ä¸åŒç§¸ç§†è¦†ç›–é‡å¯¹çŽ‰ç±³äº§é‡åŠå ¶ç¨³å®šæ€§çš„å½±å“.

Clarifying the differences of maize yield and its stability under long-term no-tillage with different stover mulching amounts can provide theoretical and technical supports for establishing and evaluating long-term conservation tillage pattern and promoting grain production. Based on a long-term conservation tillage field experiment in the mollisol area of Northeast China since 2007, we analyzed the interannual variation, variation coefficient and stability of maize yield during 2013 and 2019 across five treatments, i.e., no-tillage stover-free mulching (NT0), no-tillage with 33% stover mulching (NT33), no-tillage with 67% stover mulching (NT67) and no-tillage with 100% stover mulching (NT100), with the traditional ridge cropping (RT) as the control. The results showed that compared with RT, long-term no-tillage with stover mulching treatments could increase maize yield. NT100 had the highest increasing rate of 11.4%, followed by NT67 and NT0, with the increasing rate of 11.0% and 10.4%, respectively. Maize yield exhibited a nonlinear relationship with the amount of stover mulch. The variation coefficient of maize yield under multi-year no-tillage with different stover mulching could be sorted as NT67NT0>NT100>RT>NT33, indicating that NT67 treatment could significantly reduce the interannual fluctuation of maize yield and had better sustainability of yield. No-tillage stover mulching significantly increased soil total carbon and total nitrogen contents, which were significantly positively correlated with maize yield. In conclusion, compared with traditional tillage, no-tillage stover mulching could increase maize yield and soil carbon and nitrogen contents. Appropriate stover mulching (NT67)had the potential to improve the stability and sustainability of maize yield.

[Interannual variation of soil organic nitrogen fractions and its response to straw returning.] / åœŸå£¤æœ‰æœºæ°®ç»„åˆ†çš„å¹´é™ å˜åŒ–åŠå ¶å¯¹ç§¸ç§†è¿˜ç”°çš„å“åº”.

Elucidating the interannual variation of soil organic nitrogen fractions and its response to straw returning is of great significance for rational regulation of soil organic nitrogen pool and sustainable soil utilization. We conducted a field microcosm experiment with typic hapludoll soil at the National Field Observation and Research Station of Shenyang Agroecosystems. Three treatments were set, including nitrogen fertilizer addition (200 kg N·hm-2, the same in other treatments), nitrogen fertilizer addition with 50% straw return, and nitrogen fertilizer addition with 100% straw return. We classified soil organic nitrogen fractions in the 1st, 3rd, 6th, and 9th years of the experiment by using the Bremner acid hydrolysis method. The results showed that the content of amino acid nitrogen increased with the tillage years, with an increase rate of 39.8% compared with 1st year. The content of hydrolyzable unknown nitrogen increased by 10.8% compared with 1st year, which reached the highest in the 3rd year. The content of total soil nitrogen and other organic nitrogen fractions showed limited variation with tillage years. The proportion of hydrolyzable total nitrogen that is relatively easy to mineralize in the total soil nitrogen gradually increased with the tillage years, and that of relatively stable acid insoluble nitrogen to total soil nitrogen gradually decreased, indicating that soil nitrogen availability increased with the tillage years, which would facilitate the soil nitrogen supply capacity. Compared with the treatment without straw returning, adding straw improved soil total nitrogen and each hydrolyzable nitrogen contents, with such positive effect be stronger under the treatment with heavier straw returning. The effect of straw returning on hydrolyzable nitrogen fractions mainly occurred in the 6th and 9th years. The components of soil total nitrogen that have been increased were mainly the amino acid nitrogen and hydrolyzed unknown nitrogen, resulting in increased proportion of hydrolyzable nitrogen. Straw returning could increase soil nitrogen pool and improve soil nitrogen conservation and supply capacity.

Two naturally derived small molecules disrupt the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) interaction to inhibit colorectal cancer cell growth.

BACKGROUND: Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth. METHODS: Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth. RESULTS: Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ±â€Š3.54 vs.1.88 ±â€Š0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ±â€Š2.03 vs. 2.22 ±â€Š0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ±â€Š1.15 µmol/L and 83.43 ±â€Š7.24 µmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo. CONCLUSIONS: Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.

[Research advances on cover crop plantation and its effects on subsequent crop and soil environment]. / è¦†ç›–ä½œç‰©çš„ç§æ¤çŽ°çŠ¶åŠå ¶å¯¹ä¸‹èŒ¬ä½œç‰©ç”Ÿé•¿å’ŒåœŸå£¤çŽ¯å¢ƒå½±å“çš„ç ”ç©¶è¿›å±•.

Cover crops are grown in temporal and spatial gaps of agricultural production to reduce or avoid soil exposure. As it can protect farmland soil from wind erosion, water erosion and human disturbance, planting cover crops is considered as a new type of conservation tillage practice. Here, we briefly introduced the planting management of cover crops, including crop species, planting modes, and the returning to farmland after their termination, which could provide a reference for efficiently planting cover crops at large scale during the fallow period. Based on domestic and foreign studies, we summarized the benefits of cover crops on agroecosystem, including cash crops, soil quality, weed control, greenhouse gas emission, and soil microbes. Our review illustrated their importance in improving soil quality and achieving sustainable agricultural development, despite the limitation of cover crops, including unobvious benefits in the short-term and the reduction of crop yield caused by improper management.