An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma.

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.

[Spatiotemporal Simulation and Prediction of Grassland Carbon Budget in Gansu Under Different Climate Scenarios].

Under the background of carbon peak and carbon neutrality, grassland carbon sinks are a key pathway to carbon neutrality. Based on the Coupled Model Intercomparison Project Phase 6 (CMIP6) climate scenario data, the Daycent model was used to simulate the carbon budget of Gansu grasslands from 2015 to 2100, and the trend analysis was used to study the spatial and temporal changes in grassland carbon budget in the next 78 years. The results revealed that, under the future climate scenario of SSP245, the net ecosystem productivity (NEP) indicated a non-significant fluctuating downward trend with a rate of -0.20 g·(m2·a)-1(in C, the same below), and the grassland carbon sink was in a declining state. Under the future climate scenario of SSP585, the grassland NEP indicated a significant fluctuating increase trend with a growth rate of 1.36 g·(m2·a)-1, and the grassland carbon sink gradually increased under this scenario; the spatial distribution of grassland carbon budget increased from northwest to southeast. The increase in temperature and precipitation under the SSP585 climate scenario was higher than that under the SSP245 climate scenario, and the grassland carbon budget strongly correlated positively with precipitation. However, a negative correlation was observed between grassland carbon budget and temperature. We identified the carbon sink intensity in Gansu grasslands under different climate conditions, which provides a reference for and contribution to effective carbon sequestration.

[Diagnosis of pleural cavity extraskeletal osteosarcoma: a case report and literature review].

OBJECTIVE: To describe the manifestations and diagnosis of pleural cavity extraskeletal osteosarcoma (ESO). METHODS: One case of ESO diagnosed at the Research Institute of Tuberculosis, 309th Hospital of PLA was reported. Six cases reported in the literature were reviewed. RESULTS: Chest CT of a middle-aged man revealed an enormous heterogeneous neoplasm, about 10.9 cm x 9.2 cm x 17.7 cm in size, in the left pleural cavity. There was abundant calcification in the tumor, with signs of invasion into the diaphragm and the pleura. Pleural effusion of the left thoracic cavity was also seen on the chest CT. Osteosarcoma was confirmed by pathological study after surgical resection of the tumor. CONCLUSIONS: ESO is a rare malignant soft tissue sarcoma. Pleural cavity ESO is insidious and imaging studies often reveal a huge mass with abundant calcification. The differential diagnosis includes benign and malignant diseases of the thorax.

Simultaneous detection of IgG and IgM antibodies against a recombinant polyprotein PstS1-LEP for tuberculosis diagnosis.

BACKGROUND: Commercial serological tests for the diagnosis of tuberculosis (TB) show poor sensitivity and specificity, and a new approach to antigen screening is required to improve the accuracy of serodiagnosis. METHODS: Using an indirect enzyme-linked immunosorbent assay (ELISA), we evaluated the responses of IgG and IgM antibodies to the recombinant PstS1-LEP protein expressed in Escherichia coli, a polyprotein of PstS1 and line multi-epitopes polypeptide (LEP). RESULTS: The mixture of anti-human IgG and IgM added to a well [Ig(G + M)], which was different from the combination of IgG and IgM (IgG + IgM), had a stronger immunoreactivity to PstS1-LEP than the single antibody. IgG and Ig(G + M), but not IgM against the PstS1-LEP protein effectively distinguished TB patients from patients with nontuberculous pulmonary disease (NTBPD) and healthy controls (HCs). Compared with IgG, the sensitivities of Ig(G + M) and IgG + IgM varied from 71.4% to 77.6% and 72.7% in pulmonary TB (PTB) patients and from 42.1% to 64.0% and 55.8% in extrapulmonary TB (EPTB) patients, respectively. The specificity of Ig(G + M) did not decrease, and was higher than that provided by IgG + IgM in HCs with positive tuberculin skin test. CONCLUSION: These findings suggest that PstS1-LEP can act as a candidate for detecting Ig(G + M) in serum from PTB and EPTB patients.

Effect of types of educational institutions on social communication functions among children with autism spectrum disorder:an observation study / 中国学校卫生

Objective@#To explore changes in the social interactions of school aged children with autism spectrum disorder (ASD) enrolled in ordinary schools and special education institutions during a one year observation period.@*Methods@#A total of 44 children with ASD were recruited from the Research Center of Children and Adolescent Psychological and Behavioral Development in the Department of Public Health, Sun Yat sen University, during 2017 and 2018. At the baseline and follow up periods, a self report questionnaire (completed by parents) was administered in order to collect demographic information related to the children, the survey included the Social Responsiveness Scale (SRS), Strengths and Difficulties Questionnaire (SDQ), Social Communication Questionnaire (SCQ), Screen for Child Anxiety Related Emotional Disorder (SCARED) and the Swan son Nolan and Pelham, Version IV Scale(SNAP-IV).@*Results@#At baseline, compared with children in ordinary schools, the total score of SRS (114.56±6.02, 93.63 ±3.82) and its subscale scores (social awareness:13.54±0.71, 11.02±0.45; social cognition:22.73±1.16, 18.19±0.73; social interaction:37.47±2.12, 30.40±1.35; autistic mannerisms: 23.11±1.70, 19.02±1.08) were higher in children attending special education institutions, as well as the SCQ total score (20.37±1.60, 12.92±1.02) and its subscale scores(social interaction domain:8.77±0.92, 4.23±0.58; social communication domain:6.07±0.55, 4.19±0.35)( P <0.05). Further comparison of baseline and follow up results showed no significant difference in time effect or in the interaction between time and the educational environment( P >0.05).@*Conclusion@#Compared with special education institutions, school aged children with ASD in ordinary schools had lower levels of social impairment. During the one year observation period, there was no correlation between the educational environment and changes in symptoms of children and their parents. Parents should choose an appropriate educational environment according to the children s abilities, and ordinary schools and teachers should be prepared for inclusive education.

Annotating images by mining image search results.

Although it has been studied for years by the computer vision and machine learning communities, image annotation is still far from practical. In this paper, we propose a novel attempt at model-free image annotation, which is a data-driven approach that annotates images by mining their search results. Some 2.4 million images with their surrounding text are collected from a few photo forums to support this approach. The entire process is formulated in a divide-and-conquer framework where a query keyword is provided along with the uncaptioned image to improve both the effectiveness and efficiency. This is helpful when the collected data set is not dense everywhere. In this sense, our approach contains three steps: 1) the search process to discover visually and semantically similar search results, 2) the mining process to identify salient terms from textual descriptions of the search results, and 3) the annotation rejection process to filter out noisy terms yielded by Step 2. To ensure real-time annotation, two key techniques are leveraged-one is to map the high-dimensional image visual features into hash codes, the other is to implement it as a distributed system, of which the search and mining processes are provided as Web services. As a typical result, the entire process finishes in less than 1 second. Since no training data set is required, our approach enables annotating with unlimited vocabulary and is highly scalable and robust to outliers. Experimental results on both real Web images and a benchmark image data set show the effectiveness and efficiency of the proposed algorithm. It is also worth noting that, although the entire approach is illustrated within the divide-and conquer framework, a query keyword is not crucial to our current implementation. We provide experimental results to prove this.

Evidence for asthma susceptibility genes on chromosome 11 in an African-American population.

Initial genome-wide scan data provided suggestive evidence for linkage of the asthma phenotype in African-American (AA), but not Caucasian, families to chromosome 11q markers (peak at D11S1985; LOD=2). To refine this region, mapping analysis of 91 AA families (51 multiplex families and 40 asthmatic case-parent trios) was performed with an additional 17 markers flanking the initial peak linkage marker. Multipoint analyses of the 51 multiplex families yielded significant evidence of linkage with a peak non-parametric linkage score of 4.38 at marker D11S1337 (map position 68.6 cM). Furthermore, family-based association and transmission disequilibrium tests conducted on all 91 families showed significant evidence of linkage in the presence of disequilibrium for several individual markers in this region. A putative susceptibility locus was estimated to be at map position 70.8 cM with a confidence interval spanning the linkage peak. Evidence from both linkage and association analyses suggest that this region of chromosome 11 contains one or more susceptibility genes for asthma in these AA families.