Causes and consequences of tipping points in river delta social-ecological systems.

The sustainability of social-ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative" or "positive" tipping points depending on actors' perspectives, e.g. regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land use. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological, and land-use management of the world's river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social-ecological systems on a pathway towards sustainable development.

TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic ß Cells from Glucose Toxicity.

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet ß cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic ß cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-ß1, TNFα, and IL-1ß. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.

Assessing the construction of a Healthy City in China: a conceptual framework and evaluation index system.

OBJECTIVES: COVID-19 has brought challenges to the health of all mankind. It is particularly important to promote the construction of a 'Healthy China' and build a 'healthy community'. The aims of this study were to construct a reasonable conceptual framework for the Healthy City concept and to assess Healthy City construction in China. STUDY DESIGN: This study combined qualitative and quantitative research. METHODS: This study proposes the concept model of 'nature-human body-Healthy City' and accordingly constructs an evaluation index system for the construction of a Healthy City that integrates five dimensions, namely, the medical level, economic basis, cultural development, social services, and ecological environment to explore the spatial and temporal heterogeneity of Healthy City construction in China. Finally, the influencing factors of Healthy City construction patterns are explored using GeoDetector. RESULTS: (1) The pace of Healthy City construction is generally on the rise; (2) the construction of Healthy Cities exhibits significant global spatial autocorrelation and gradually increasing agglomeration. The spatial distribution of cold hotspot areas was relatively stable; (3) medical and health progress is an important factor; the level of economic development is the leading support; the endowment of resources and environment is the basic condition; public service support provides important support; and scientific and technological innovation capabilities provide technical support for the construction of a Healthy City. CONCLUSIONS: The spatial heterogeneity of Healthy City construction in China is evident, and the state of spatial distribution is relatively stable. The spatial pattern of Healthy City construction is shaped by a combination of factors. Our research will provide a scientific basis for promoting the construction of Healthy Cities and helping to implement the Health China Strategy.

A radiomics model development via the associations with genomics features in predicting axillary lymph node metastasis of breast cancer: a study based on a public database and single-centre verification.

AIM: To evaluate the predictive performance of the radiomics model in predicting axillary lymph node (ALN) metastasis through the associations between radiomics features and genomic features in patients with breast cancer. MATERIALS AND METHODS: Patients with breast cancer were enrolled retrospectively from a public database (111 patients as training group) and one hospital (15 patients as external validation group). The genomics features from transcriptome data and radiomics features from dynamic contrast-enhanced magnetic resonance imaging (MRI) were collected. Firstly, overlapping genes were identified using the Kyoto Encyclopedia of Genes and Genomes and differentially expressed gene analysis, while radiomics features were reduced using a data-driven method. Then, the associations between overlapping genes and retained radiomics features were assessed to obtain key pairs of radiomics-genomics features. Furthermore, the least absolute shrinkage and selection operator (LASSO) algorithm was used to detect the key-pairs features. Finally, radiomics and genomics models were constructed to predict ALN metastasis. RESULTS: After using the hybrid data- and gene-driven selection method, key pairs of features were detected, which consisted of six radiomic features associated with four genomic features. The radiomics model exhibited comparable performance to the genomics model in predicting ALN metastasis (radiomic model: area under the curve [AUC] = 0.71, sensitivity = 77%, specificity = 56%; genomic model: AUC = 0.72, sensitivity = 85%, specificity = 74%). The four genomic features were enriched in six pathways and related to metabolism and human diseases. CONCLUSION: The radiomics model established using the gene-driven hybrid selection method could predict ALN metastasis in breast cancer, which showed comparable performance to the genomics model.

Impact of angiogenic inhibition in the treatment of newly diagnosed and recurrent glioblastoma: a meta-analysis based on randomized controlled trials.

OBJECTIVE: Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the central nervous system in adults with high recurrence and mortality rates. Although radiotherapy and temozolomide have become the standard therapeutic regimen for GBM as adjuvant chemoradiotherapy after surgical resection, clinical outcomes remain suboptimal. In recent years, targeted antiangiogenic therapy has attracted considerable attention, but its therapeutic efficacy and safety are still controversial. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of chemoradiotherapy with or without bevacizumab for the treatment of glioblastoma were collected by searching on the Pubmed, Embase, Cochrane, Ovid, Scopus, Web of Science, and Google Scholar databases from the date of database establishment to February 2022. Meta-analysis was performed using RevMan 5.3 software after two investigators independently screened the literature, extracted data, and assessed the risk bias of included studies. RESULTS: A total of 7 RCTs were included. The meta-analysis showed that bevacizumab in combination with chemoradiotherapy was superior to chemoradiotherapy alone in terms of progression-free survival (PFS), with a statistically significant difference. Interestingly, bevacizumab in combination with chemoradiotherapy improved PFS more significantly in recurrent glioblastoma than in newly diagnosed glioblastoma. However, for overall survival (OS), the combination of bevacizumab with chemoradiotherapy was similar to chemoradiotherapy alone, which was not significantly different. With regard to safety, the incidence of most adverse events was higher in the combination of bevacizumab and chemoradiotherapy than in chemoradiotherapy alone, especially in terms of hematologic adverse events. CONCLUSIONS: Current evidence suggests that angiogenesis inhibitor-containing chemoradiotherapy regimens are preferentially recommended for patients with recurrent glioblastoma to prolong their progression-free survival, provided that safety is acceptable, but this does not confer a significant benefit on overall patient survival.

[Association between dietary vitamin A intake and gestational diabetes mellitus in the first trimester].

Objective: To investigate the relationship between dietary vitamin A intake and its sources in the first trimester and gestational diabetes mellitus (GDM). Methods: A prospective study was conducted to select women at 6-14 weeks of gestation in an obstetric clinic of a maternal and child health care medical institution in Chengdu in 2017. The types and quantities of food during the first trimester were collected by 3-day 24-hour dietary recalls. Dietary vitamin A intake was calculated based on the Chinese Food Composition Table (2018), and it was divided into animal and plant vitamin A intakes according to its food sources. An oral glucose tolerance test was performed at 24-28 weeks of gestation to diagnose GDM according to the Chinese guidelines for diagnosis and treatment of gestational diabetes mellitus (2014). According to the estimated average requirement (EAR) and recommended nutrient intake (RNI), dietary vitamin A intake was divided into low-level group (RNI). Animal and plant vitamin A intakes were divided into four groups (Q1-Q4) according to the quartile method, respectively. The association between dietary vitamin A intake, its different sources of vitamin A intake and GDM in the first trimester was analyzed by log-binomial regression models. Results: A total of 1 298 valid samples were finally included. The average dietary vitamin A intake, animal and plant vitamin A intakes in the first trimester were 341.1 (227.8-501.0) µgRAE/d, 139.3 (69.6-195.3) µgRAE/d and 184.2 (99.4-301.1) µgRAE/d, respectively. After adjusting for confounding factors, log-binomial regression analysis showed that the risk of GDM in high-level group of dietary vitamin A intake was lower than that in low-level group [RR (95%CI):0.53 (0.36-0.80)]. Pregnant women in the highest quartile of animal vitamin A intake had a lower risk of GDM than those in the lowest quartile [RR (95%CI):0.66 (0.47-0.95)]. No relationship between plant vitamin A intake and GDM was found. Conclusion: Dietary vitamin A intake in the first trimester is associated with the occurrence of GDM, and higher intake than RNI may reduce the risk of GDM. Higher vitamin A intake from animal-derived food is associated with decreased risk of GDM.

Docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer: a meta-analysis.

OBJECTIVE: Although bevacizumab and trastuzumab have been widely added to the standard regimen for metastatic breast cancer, the clinical outcomes remain controversial. The purpose of this study was to conduct meta-analysis to verify the clinical efficacy and safety of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: All available literature of clinical trials about docetaxel, bevacizumab, trastuzumab and metastatic breast cancer was pooled from PubMed, Embase and Cochrane library database. The meta-analysis combined the progression free survival (PFS), overall response rate (ORR) and incidence of all grades adverse events in MBC patients. RESULTS: Seven clinical trials were included by two reviewers. Docetaxel and bevacizumab with trastuzumab show the pooled PFS was 16.53 months (95% CI: 13.95-19.11 months), the pooled ORR was 0.75 (95% CI: 0.69-0.80) in HER2-positive MBC patients. Docetaxel and bevacizumab show that the pooled PFS was 8.49 months (95% CI: 7.80-9.18 months), the pooled ORR was 0.51(95% CI: 0.47-0.55) in HER2-negative MBC patients. CONCLUSIONS: Both for patients with HER2-positive and negative metastatic breast cancer, docetaxel and bevacizumab with or without trastuzumab as first-line treatment resulted in long survival, especially in terms of progression-free survival. Although the overall response rates are also significantly improved, it is still controversial based on the current evidence.

[Value of PET/MRI in the diagnosis of malignant pleural effusion in comparison with PET/CT].

Objective: To investigate the diagnostic value of PET/MRI for malignant pleural effusion (MPE), and compare its diagnostic difference with PET/CT. Methods: The data of 57 patients with suspected MPE admitted into Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from October 2017 to January 2020 was analyzed. A total of 53 patients were included in the prospective study, and the whole body PET/CT and thoracic PET/MRI were performed on them respectively. Two physicians used a blind method to evaluate the morphological features of PET/CT and PET/MRI images, delineate the region of interest (ROI), obtain the maximum standard uptake value (SUVmax) of the ROI in the PET/CT and PET/MRI images. The target-to-background ratio (TBR) of the lesion was calculated. The diffusion-weighted imaging (DWI) characteristics of the pleura in PET/MRI images were analyzed. Taking pathological diagnosis as the gold standard, the diagnostic effect of PET/CT and PET/MRI on MPE were evaluated. Results: The 53 patients who were finally included were (62.8±1.7) years old, consisting of 31 males. Pathological results showed that 41 cases were MPE and 12 cases were benign pleural effusion (BPE). There were no statistical differences in age, gender and smoking history between the two groups (P>0.05). Bland-Altman analysis showed that the SUVmax of pleural lesions by PET/MRI was higher than that by PET/CT (6.4±0.6 vs 5.3±0.5, P<0.001). The TBR of PET/MRI was higher than that of PET/CT (2.2±0.2 vs 1.8±0.2, P<0.001). The sensitivity, specificity, and accuracy of PET/MRI in the diagnosis of MPE by combining imaging features such as SUVmax and DWI of pleural lesions were 75.6%, 100%, and 81.1%, respectively. The sensitivity, specificity, and accuracy of PET/CT combined with SUVmax and imaging features of pleural lesions in the diagnosis of MPE were 85.4%, 83.3%, and 77.4%, respectively. There was no statistically significant difference between PET/MRI and PET/CT in the area under the curve (AUC) for diagnosing MPE (0.934 vs 0.873, P>0.05). Conclusions: PET/MRI and PET/CT have the equivalent diagnostic efficiency for MPE. However, PET/MRI shows higher SUVmax and TBR for pleural lesions, and has specific pleural DWI imaging characteristics, which is worthy of further clinical research.

Improved Constraints on Global Methane Emissions and Sinks Using δ 13C-CH4.

We study the drivers behind the global atmospheric methane (CH4) increase observed after 2006. Candidate emission and sink scenarios are constructed based on proposed hypotheses in the literature. These scenarios are simulated in the TM5 tracer transport model for 1984-2016 to produce three-dimensional fields of CH4 and δ 13C-CH4, which are compared with observations to test the competing hypotheses in the literature in one common model framework. We find that the fossil fuel (FF) CH4 emission trend from the Emissions Database for Global Atmospheric Research 4.3.2 inventory does not agree with observed δ 13C-CH4. Increased FF CH4 emissions are unlikely to be the dominant driver for the post-2006 global CH4 increase despite the possibility for a small FF emission increase. We also find that a significant decrease in the abundance of hydroxyl radicals (OH) cannot explain the post-2006 global CH4 increase since it does not track the observed decrease in global mean δ 13C-CH4. Different CH4 sinks have different fractionation factors for δ 13C-CH4, thus we can investigate the uncertainty introduced by the reaction of CH4 with tropospheric chlorine (Cl), a CH4 sink whose abundance, spatial distribution, and temporal changes remain uncertain. Our results show that including or excluding tropospheric Cl as a 13 Tg/year CH4 sink in our model changes the magnitude of estimated fossil emissions by ∼20%. We also found that by using different wetland emissions based on a static versus a dynamic wetland area map, the partitioning between FF and microbial sources differs by 20 Tg/year, ∼12% of estimated fossil emissions.

[Analysis of the clinical characteristics and prognosis of 36 cases of newly diagnosed multiple myeloma patients with bone marrow monoclonal plasma cell ratio of less than 10].

Objective: To improve the understanding of newly diagnosed multiple myeloma (NDMM) patients with bone marrow (BM) monoclonal plasma cell ratio of less than 10%. Methods: The clinical characteristics, laboratory examination, response to treatment, and prognosis of 36 NDMM patients with BM plasma cell ratio of less than 10% at Peking Union Medical College Hospital from January 2009 to December 2017 were summarized retrospectively. In the same period, other age- and gender-matched 72 NDMM patients were selected as the control group, whose BM plasma cell ratio was equal to or greater than 10%. Results: First, the patients in the study group accounted for 4.4% of the whole MM population (36/818) , among which only 11 (30.6%) were classified as International Staging System (ISS) Ⅲ, which was significantly lower than that in the control group[45 (62.5%) ] (P=0.002) . Extramedullary disease (EMD) was more common in the study group (33.3%vs 5.6%, P<0.001) . The median quantity of serum M protein (g/L) in the less than 10% group was 1.04 (0-50.10) , which was significantly lower than that in the control group [4.50 (0-63.10) ] (P=0.016) , similar to the median quantity of 24-h urinary light chain (510 mg vs 2800 mg, respectively, P=0.023) . Second, the median progression-free survival (PFS) times of front-line regimen in the study and control groups were 26.4 and 19.9 months, respectively (HR=1.703, 95%CI 0.167-0.233, P=0.002) . In addition, the overall survival (OS) times were 65.8 and 46.2 months, respectively (HR=2.626, 95%CI 0.439-0.541, P=0.058) . Third, the study group was reclassified based on the quantity of M protein. The median OS times in patients with low/high tumor load were 66.4 and 24.0 months, respectively (HR=2.349, 95%CI 0.603-0.696, P=0.046) . The median PFS times were 33.1 and 15.5 months, respectively (HR=1.806, 95%CI 0.121-0.399, P=0.077) . Bortezomib-based regimens did not affect the clinical outcomes. Conclusion: The subpopulation of patients with MM with BM monoclonal plasma cell ratio less than 10% has specific clinical characteristics, including an early disease stage and a lower overall tumor load. Although more patients of this minor group presented with an extramedullary disease, their response rate to the initial treatment and survival outcome are better than those of patients with BM monoclonal plasma cell ratio more than 10%.

[The clinical manifestations and risk factors in primary antiphospholipid syndrome with thrombocytopenia].

Objectives: To cross-sectionally analyze the clinical characteristics of primary antiphospholipid syndrome (PAPS) patients with thrombocytopenia, risk factors associated with thrombocytopenia, and risk of symptom recurrence in these patients. Methods: The inpatients with PAPS were retrospectively analyzed in Peking Union Medical College Hospital from 2009 to 2019. Using the collected clinical and laboratory data, the clinical characteristics and risk of symptom recurrence in the PAPS patients with thrombocytopenia were compared with those in the PAPS patients with normal platelet counts. Univariate and multivariate logistic regression analyses were performed to screen the risk factors for thrombocytopenia. Results: In this study, 127 patients with PAPS were enrolled, of which 36 (28.3% ) had thrombocytopenia, with a median age of 38 years, and 63.9% were female. In the thrombocytopenia group, the average platelet count was (58.9±27.0) ×10(9)/L, and the prevalence of thrombosis and morbid pregnancy was not significantly different from that in the normal platelet group. However, the thrombocytopenia group had higher incidence rate of autoimmune hemolytic anemia (19.4% vs 3.3% ) , livedo reticularis (16.7% vs 3.3% ) , chronic kidney disease (25% vs 8.8% ) and antiphospholipid antibodies triple positiveness (61.1% vs 37.4% ) , lower complement levels (C3 of 0.87 g/L vs 1.07 g/L, C4 of 0.12 g/L vs 0.18 g/L, P<0.05) , and higher adjusted Global APS Score (median score of 13 vs 9, P=0.037) than the normal platelet group. In multivariate logistic regression analysis, hypocomplementemia (OR value 5.032, 95% CI 3.118-22.095) is an independent risk factor for thrombocytopenia. Conclusions: In patients with PAPS, thrombocytopenia is mostly mild to moderate. Hypocomplementemia may be the independent risk factor for thrombocytopenia in PAPS patients. The PAPS patients with thrombocytopenia may have a higher risk of symptom recurrence.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

[Short-term outcomes of single incision plus one port laparoscopic surgery for colorectal cancer].

Objective: Although single port laparoscopic surgery has achieved good clinical results, many surgeons are discouraged by the difficulties of operation, conflict of instruments, lack of antagonistic traction, and straight-line perspective. Therefore, some surgeons have proposed a single incision plus one hole laparoscopic surgery (SILS+1) surgical method. This study explored the safety and feasibility of SILS+1 for radical resection of colorectal cancer. Methods: A descriptive cohort study was carried out. The clinical data, including the operation, pathology and recovery situation, of 178 patients with colorectal cancer undergoing SILS+1 at Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2018 to January 2019 were prospectively collected and retrospectively analyzed. Clavien-Dindo criteria was used for postoperative complication evaluation and visual analog scale was used for pain standard. Follow-up studies were conducted through outpatient service or telephone and the follow-up period was up to May 2019. Results: A total of 178 patients with colorectal cancer underwent SILS+1, including 111 male patients (62.4%) with an average age of 59 years. Eleven (6.2%) patients received added 1-3 operation ports during operation, and 1 patient was converted to open surgery due to ileocolic artery hemorrhage. The operative time was (135.2±42.3) minutes. The intraoperative blood loss was (34.6±35.5) ml. The number of harvested lymph nodes was 33.1±17.6. The distal margin was (4.7±17.8) cm. The proximal margin was (10.2±5.3) cm. Operation-related complications were observed in 16 patients (9.0%) within 30 days after the operation, of whom 6 had Clavien-Dindo III complications (3.4%). The postoperative pain scores were lower than 3. The average postoperative hospital stay was (5.6±2.6) days. Three patients (1.7%) returned to hospital within 30 days after operation due to intestinal obstruction and infection around stoma. The cosmetic evaluation of all the patients was basically satisfied. Conclusion: SILS+1 is safe and feasible in the treatment of colorectal cancer, and can reduce the postoperative pain.

Effects of oral sialic acid on gut development, liver function and gut microbiota in mice.

Sialic acid (N-acetylneuraminic acid), a 9-carbon monosaccharide, has been widely studied in immunology, oncology and neurology. However, the effects of sialic acid on organ and intestinal development, liver function and gut microbiota were rarely studied. In this study, we found that oral sialic acid tended to increase the relative weight of liver and decreased the serum aspartate aminotransferase (GPT) activity. In addition, sialic acid treatment markedly reduced gut villus length, depth, the ratio of villus length/depth (L/D), areas, width and the number of goblet cells. Furthermore, gut microbes were changed in response to oral sialic acid, such as Staphylococcus lentus, Corynebacterium stationis, Corynebacterium urealyticum, Jeotgalibaca sp_PTS2502, Ignatzschineria indica, Sporosarcina pasteurii, Sporosarcina sp_HW10C2, Facklamia tabacinasalis, Oblitimonas alkaliphila, Erysipelatoclostridium ramosum, Blautia sp_YL58, Bacteroids thetaiotaomicron, Morganella morganii, Clostridioides difficile, Helicobacter tryphlonius, Clostridium sp_Clone47, Alistipes finegoldii, [pseudomonas]_geniculata and Pseudomonas parafulva at the species level. In conclusion, oral sialic acid altered the intestinal pathological state and microbial compositions, and the effect of sialic acid on host health should be further studied.

Quantitative proteomics analysis reveals the response mechanism of peanut (Arachis hypogaea L.) to imbibitional chilling stress.

Imbibitional chilling stress inhibits normal seed germination and seedling establishment and leads to large losses in peanut production. This is a major limiting factor when sowing peanut earlier and further north. To reveal the response mechanism of peanut to imbibitional chilling stress, a Tandem Mass Tag (TMT)-based quantitative proteomics analysis was conducted to identify differentially accumulated proteins (DAPs) under imbibitional chilling stress. Hormone profiling and transcriptional analysis were performed to confirm the proteomics data. Further seed priming analysis with exogenous cytokinins was conducted to validate the role of cytokinins in alleviating imbibitional chilling injury. A total of 5029 proteins were identified and quantified in all of the experimental groups. Among these, 104 proteins were DAPs as compared with the control. Enrichment analysis revealed that these DAPs were significant in various molecular functional and biological processes, especially for biosynthesis and metabolism of plant hormones. Hormone profiling and transcription analysis suggested that the reduced abundance of cytokinin oxidase may be caused by down-regulation of gene expression of the corresponding genes and leads to an elevated content of cytokinins under chilling stress. Seed priming analysis suggested that exogenous application of cytokinins may alleviate injury caused by imbibitional chilling. Our study provides a comprehensive proteomics analysis of peanut under imbibitional chilling stress, suggesting the role of plant hormones in the response mechanism. The results provide a better understanding of the imbibitional chilling stress response mechanism in peanut that will aid in peanut production.

The KMT2A gene: mRNA differential expression in the ovary and a novel 13-nt nucleotide sequence variant associated with litter size in cashmere goats.

A genome-wide association study had shown that lysine methyltransferase 2A (KMT2A), which encodes the histone 3 lysine 4 methyltransferase and reportedly can regulate gametogenesis, steroidogenesis, and development as well as other biological processes, is a potential candidate gene influencing litter size in the dairy goat, suggesting its key function in animal reproduction. Here, we aimed to explore the genetic effects of the KMT2A gene on litter size in females of the Chinese indigenous cashmere goat, using a large sample size (n > 1,000), based on their levels of RNA transcription and DNA variation. First, mRNA expression levels of this gene in ovarian tissues between the low-prolific group (first-born litter size = 1) and high-prolific group (first-born litter size ≥2) were significantly different, revealing the potential functioning of KMT2A in goat prolific. Moreover, a novel 13-nt nucleotide sequence variant was identified in Shaanbei white cashmere goats (n = 1,616). In accordance with the independent chi-square (χ2) analysis, the distribution of genotypes (P = 2.57 × 10-9) and allelotypes (P = 3.00 × 10-7) between the low- and high-prolific groups differed significantly, indicating the 13-nt mutation was associated with litter size. Further analysis showed that the insertion/insertion (II) genotype was significantly different with insertion/deletion (ID) (P = 1.76 × 10-9) and deletion/deletion (DD) (P = 7.00 × 10-6), with goats having the DD genotype producing an average litter size larger than the other genotypes. Taken together, these findings suggest KMT2A can serve as a candidate gene for breeding goats, which may have implications for improving the future development of the goat industry.

MiR-503 Contributes to Glucocorticoid Sensitivity in Acute Lymphoblastic Leukaemia via Targeting WNT3A.

Abnormal accumulation of lymphoblasts in the blood and bone marrow is the main characteristic of acute lymphoblastic leukaemia (ALL). Glucocorticoids are effective drugs for ALL, while glucocorticoid resistance is an obstacle to ALL therapy. MicroRNAs (miRNAs) are implicated in the drug resistance and modulate the response of ALL to glucocorticoids. The role of miR-503 in glucocorticoid sensitivity of ALL was investigated in this study. Firstly, T-leukaemic cells were isolated from patients with ALL. The human ALL cell line (CCRF/CEM) was incubated with dexamethasone to establish a glucocorticoid- resistant ALL cell line (CCRF/CEM-R). Data from MTT showed that IC50 (50% inhibitory concentration) of dexamethasone in T-leukaemic cells isolated from glucocorticoid-resistant ALL patients or CCRF/CEM-R was increased compared with IC50 in T-leukaemic cells isolated from glucocorticoid- sensitive ALL patients or CCRF/CEM. MiR- 503 was down-regulated in glucocorticoid-resistant leukaemic cells and CCRF/CEM-R. Secondly, overexpression of miR-503 sensitized CCRF/CEM-R to dexamethasone. Moreover, over-expression of miR- 503 also promoted the sensitivity of ALL cells to dexamethasone. Thirdly, miR-503 bound to WNT3A mRNA and negatively regulated the expression of WNT3A. Over-expression of miR-503 reduced protein expression of nuclear ß-catenin, and over-expression of WNT3A attenuated the miR-503 overexpression- induced decrease in nuclear ß-catenin. Lastly, the over-expression of miR-503-induced increased sensitivity of ALL-resistant cells and CCRF/ CEM-R to dexamethasone was attenuated by overexpression of WNT3A. In conclusion, miR-503 targeted WNT3A mRNA to sensitize ALL cells to glucocorticoids through inactivation of the Wnt/ß-catenin pathway.

Leukocyte immunoglobulin-like receptor A3 is increased in IBD patients and functions as an anti-inflammatory modulator.

Growing evidence shows that a homozygous 6·7-kb deletion of the novel anti-inflammatory molecule leukocyte immunoglobulin-like receptor A3 (LILRA3) is associated with many autoimmune disorders. However, its effects on pathogenesis of inflammatory bowel disease (IBD) have yet not been clarified. LILRA3 is mainly expressed in monocytes, whereas its effects on biological behaviors of monocytes have not been systematically reported. In our study, to investigate the association between LILRA3 polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in 378 IBD patients and 509 healthy controls. Quantitative real time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC) were employed to detect the LILRA3 expression in IBD patient blood and intestinal samples. The human U937 monocyte cell line was employed to establish LILRA3 over-expressing cells and the effects of LILRA3 on the biological behaviors of U937 cells were systematically explored. Although no association of the polymorphism with IBD development was found, LILRA3 expression was markedly increased in IBD patients compared with healthy controls. Over-expression of LILRA3 in monocytes led to significant decreases in secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-6. Additionally, LILRA3 abated monocyte migration by reducing the expression of several chemokines and enhanced monocyte phagocytosis by increasing CD36 expression. Furthermore, LILRA3 promoted monocyte proliferation through a combination of Akt and extracellular receptor kinase/mitogen-activated protein kinase (Erk/MEK) signaling pathways. We report for the first time, to our knowledge, that LILRA3 is related to IBD and functions as an anti-inflammatory modulator in U937 cells.

[Clinical application of the gasless unilateral axillary approach in endoscopic thyroid surgery].

Objective: To investigate the efficacy, safety and advantages of gasless unilateral axillary approach (GUAA) in endoscopic thyroid surgery. Methods: A total of 334 patients who underwent the GUAA endoscopic thyroid surgery (GUAA group) or conventional open thyroid surgery (OS group) in the Department of Head and Neck Surgery of Zhejiang Cancer Hospital from January 2017 to June 2018 were retrospectively analyzed. There were 45 males and 289 females, aged from 12 to 72 years old, of whom 139 patients were assigned to GUAA group and 195 patients to OS group. Pathological results included papillary thyroid carcinoma (282 cases), nodular goiter (41 cases) and thyroid adenoma (11 cases). Surgical exploration development curve of GUAA group was drawn and was divided into two parts: the technical exploration stage and the technical stable stage. Surgical efficiency, incidences of complications, and incision satisfaction were compared between GUAA group in technical stable stage and OS group. SPSS 25.0 software was adopted for statistical analysis. Results: The mean age in GUAA group was younger than that in OS group, with a significant difference [(35.3±9.5) years vs. (48.1±10.6) years, t=11.31, P<0.01]. The cases in the endoscope group were divided into technical exploration stage for 51 cases and technical stable stage for 88 cases according to the exploration and development curve. In unilateral radical thyroidectomy and unilateral thyroid lobectomy, the mean operation time [(90.6±18.6) min and (93.5±22.0) min] and postoperative drainage volumes [(121.5±87.6) ml and (155.5±69.1) ml] of GUAA group in the stable stage were more than those of OS group [(61.6±15.6) min and (46.5±8.4) min] and [(93.2±42.3) ml and (78.9±48.7) ml]. The difference was statistically significant (t=12.28, 7.23, 3.35 and 3.05 respectively, all P<0.05), but there were no significant differences in surgical bleeding volumes between two groups [(12.7±6.8) ml vs. (13.5±7.7) ml, t=0.74, P>0.05 and (16.3±14.1) ml vs. (11.9±5.1) ml, t=1.05, P>0.05]. Compared with OS group, GUAA group had the lower incidence of anterior cervical discomfort during swallowing (2.3% vs. 29.2%, P<0.01) and the higher incision satisfaction score (1.1±0.5 vs. 2.8±0.7, t=21.12, P<0.01), however, GUAA group had the higher incidence of supraclavicular (or infraclavicular) numbness after surgery (5.7% vs. 0, P<0.01). And there was no significant difference in the incidences of temporary recurrent laryngeal nerve injury, bleeding, hematoma, infection, lymphatic leakage or chylous leakage after surgery between two groups (P>0.05). Conclusion: GUAA endoscopic thyroid surgery is a safe method with high cosmetic satisfaction.