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Coal mining disturbs surface ecosystems in coal mining subsidence areas. Based on the groundwater-surface composite ecosystem analysis, we constructed an ecological disturbance evaluation index system (18 indices) in a coal mining subsidence area using the analytic hierarchy process (AHP). Taking the Nalinhe mining area in Wushen Banner, China, in 2018-2020 as an example, the ecological disturbance degree and the weight and correlation of different indicators were determined by implementing fuzzy mathematics, weighting method, and correlation analysis method. After two years of mining, ecological disturbance was the highest in the study area (Grade III) and the lowest in the non-mining area (Grade I). The ecological disturbance in the coal mining subsidence area continued increasing over two years due to coal mining. The ecological disturbance by coal mining cannot be completely mitigated by relying on the self-repair capability of the environment. Coal mining not only directly interfered with the environment, but also strengthened the connection of different ecological indicators, forming multiple ecological disturbance chains such as "coal mining–surface subsidence–soil chemical factors," "natural climate–soil physical factors–soil chemical factors," and "mining intensity–mining thickness–burial depth and mining thickness ratio”; the last disturbance chain increased the ecological disturbance caused by resource mining. The disturbance chain "coal mining–surface subsidence–soil chemical factors" plays a leading role in controlling the ecological disturbance of soil chemical factors. The disturbance chain that controls the ecological component factors in the region remains unknown; however, the analysis of the results reveals that ecological component factors is the most important factor that hinders the restoration of the ecological state in the coal mining subsidence area. This study is of great significance for ecological restoration and governance of coal mining subsidence areas.

To investigate the prevalence of vitamin A and vitamin D deficiency and the associated factors in hospitalized neonates in Xi'an, China.A total of 524 hospitalized neonates were collected in this study. Serum vitamin A and D concentrations were detected in neonates within two weeks of birth.Serum vitamin A and D concentrations of hospitalized neonates were 0.55±0.21 μmol/L and 42.0±20.6 nmol/L, respectively. They were greater in full-term neonates than in preterm neonates, greater in rural neonates than in urban, and greater in single than in twin (all p0.001). The prevalence of vitamin A and D deficiency were 14.9% and 33.0%, the prevalence of marginal vitamin A deficiency was 64.7%, and vitamin D insufficiency was 35.1%. Neonatal serum vitamin A and D concentrations were all positively correlated with birth weight and gestational age. Neonatal serum vitamin D concentration was also positively correlated with maternal serum vitamin D concentration. Additionally, neonatal vitamin A concentration was positively correlated with neonatal serum vitamin D concentration.Vitamin A and vitamin D statuses are compromised in hospitalized neonates in Xi'an, especially in premature neonates, low birth weight neonates, twins, and those born in urban areas. Individualized supplementation with vitamin A and vitamin D in neonates should be a clinical consideration.

Batch distillation is widely applied in the fine chemical industry due to the market demand for low-volume and high-value-added products. Heterogeneous ternary mixtures with two minimum boiling azeotropes, such as cyclohexane-acetonitrile-toluene, are common in production processes. However, the separation of a mixture based on batch distillation was rarely studied because of the complexity of the method. In this work, a double-column batch stripper (with a decanter) process with a processing capacity of 7200 kg was designed for the separation of a cyclohexane-acetonitrile-toluene ternary mixture by considering the heterogeneous properties of the components. The feasibility of the process was analyzed according to the phase diagram, and the production sequence was determined. The pressure of the columns and the decanter temperature were determined synthetically from the minimum total annual cost, operation time and recovery ratio. The production time of different components, which has significant impacts on the purity and yield, was determined. In view of the situation that two separated components would be successively obtained at the bottom of each column, a control strategy was designed which can switch the products vessels automatically and control the batch distillation process. The results show that the control structure exhibits a good controllability, and the purities of the separated products are all over 99.9 mol%. Based on the optimal batch distillation process, the environmental impacts of the process were calculated. The results of the environmental analysis show that the global warming potential (GWP), acid potential (AP) and human toxicity potential (HTP) are 8613.91 kg CO2 eq, 15.40 kg SO2 eq and 267.21 kg DCB eq, respectively.

N-propanol and benzene are important chemical organic compounds, which widely exist in wastewater of chemical industry, medicine and other fields. Because they form azeotrope with water, extractive distillation was used to separate them. In order to increase the efficiency of energy utilization, vapor recompression technology was added on the basis of extractive distillation. On the basis of vapor recompression assisted extractive distillation, energy integration was carried out according to pinch technology, and the optimal energy utilization method was found. The exergy loss and gas emission of each process were studied and analyzed. The results show that the vapor recompression assisted distillation process with feed preheating can reduce the heat duty and gas emissions, and improve exergy efficiency and economic performance. Therefore, the vapor recompression assisted distillation process with feed preheating can effectively treat the wastewater containing benzene / n-propanol. It has the advantages of low cost, energy saving and environmental protection, which is of great significance to the development of environmental protection industry.

BACKGROUND: This study aims to identify the feasibility of uniportal video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) compared with multiportal VATS in the resection of mediastinal lesions. METHODS: Patients who underwent mediastinal lesion resection were enrolled and allocated to the uni-VATS, tri-VATS, and RATS groups according to the surgical approach. Propensity score-matched (PSM) analysis was performed between the VATS and RATS groups as well as the uni-VATS and tri-VATS groups. The operative and recovery parameters were compared. RESULTS: Totally, 274 patients were enrolled. There was no difference in the operative parameters among the groups. Compared with multiportal VATS, uniportal VATS and RATS had a significantly shorter chest tube placement time (2.43±0.88 vs. 1.78±1.22 vs. 2.21±1.11 days, P

The impact of coal mining subsidence on surface ecology involves the influence of several ecological elements such as water, soil, and vegetation, which is systematic and complex. Given the unclear understanding of the synergistic change patterns of the water-soil-vegetation ecological elements in the influence of coal mining in the west, this paper investigates the impact of coal mining on the surface ecology, especially the distribution of soil water content (SWC). In 2020, this study collected 3000 soil samples from 60 sampling points (at depth of 0-10 m) and tested the SWC. All samples come from three different temporal and spatial areas of coal mining subsidence in the desert mining area of Northwest China where soil types are mainly aridisols. At the same time, the interactions among deep SWC and surface soil physical and chemical properties, surface SWC and soil fertility, and pH were analyzed. The spatial variability of soil moisture is reflected by kriging interpolation, and SWC values at different depths are predicted as a basis for monitoring the environmental impact of different coal mining subsidence years. The research has shown that the ground subsidence leads to a decrease in SWC value and changes in surface soil pH, physical and chemical properties, and covering vegetation, which have occurred from the beginning of coal mining. The impact of coal mining on the SWC of the unsaturated zone is mainly at the depth of 0-6 m, where SWC is not directly related to the nutrient content of the surface soil. The overall settlement of the ground will stir up simultaneous decline in the quality of deep SWC and topsoil. The findings of this investigation suggest that changes in the soil structure caused by coal mining subsidence are the key factor in SWC loss. Timely monitoring and repairing 0-6 m ground fissures, as well as selecting shrubs on the surface is the best choice for the restoration of the ecological environment and prevention of soil erosion in this area.

Sepsis is one of the most common causes of death in ICU and especially is a harmful and a life-threatened disease to pediatrics in the world. It has been demonstrated that IL-3 plays an essential role in the processing of sepsis and the inhibition of IL-3 may alleviate sepsis progress. In our previous study, we selected a novel CD123 aptamer successfully which could inhibit the interaction of CD123 and IL-3. The aim of this study is to explore the protection ability of the first thioaptamer SS30 against sepsis in a cecal ligation and puncture (CLP) rat model. Serum IL-3 level of sepsis patients was assessed by ELISA. CLP rat model was applied in all experimental groups. CD123 thioaptamer SS30 and CD123 antibody were used to block the recognition between IL-3 and CD123. Body weight, temperature, blood gas, MAP, and serum cytokines of four grouped rats were assessed. Flow cytometry was utilized to evaluate JAK2 and STAT5 proteins. After the administration of SS30 or CD123 antibody, the rats in SS30 and CD123 antibody group had lower cytokines values(lactate, TNF-α, IL-1β, and IL-6), whereas exhibited higher value of core temperature, MAP, PO2/FiO2, and ETCO2 than those in the CLP group. The expression level of phosphorylated JAK2 and STAT5 was declined and the survival rate of rats was increased. In addition, the protection ability of SS30 was better than CD123 antibody. Therefore, CD123 thioaptamer SS30 could reduce mortality by down-regulating the phosphorylated JAK2/STAT5 signaling pathway, and reduce serum cytokines which involving in sepsis development in CLP rat model.

More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-specific pattern of metastasis in 1889, now known as the "seed and soil" theory where distinct cancer types are found to metastasize to different tumor-specific sites. Our understanding of the biology of tumor metastasis and specifically the molecular mechanisms driving their formation are still limited, in particular, as it relates to the genesis of oligometastasis. In the following review, we discuss recent advances in general understanding of this metastatic behavior including the role of specific signaling pathways, various molecular features and biomarkers, as well as the interaction of carcinoma cells with their tissue microenvironments (both primary and metastatic niches). The unique features that underlie OMD provide potential targets for localized therapy. As it relates to clinical practice, OMD is emerging as treatable with surgical resection and/or other local therapy options. Strategies currently being applied in the clinical management of OMD will be discussed including surgical, radiation-based therapy, ablation procedures, and the results of emerging clinical trials involving immunotherapy.

In order to understand the strategy of Scrippsiella acuminata to cold dark environment, the antioxidant responses and the formation of pellicle cysts of S. acuminata to darkness at 8°C and 20°C were investigated. Cell densities decreased significantly after 96 h dark treatment, and no live cells were observed after 9-days dark treatments. The darkness stress generally resulted in an increase of antioxidant defenses, including soluble protein, superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). Cellular soluble protein and SOD activity increased sharply under 20°C darkness, which protected algal cells against the oxidative stress from darkness, and resulted in relatively lower MDA levels. Soluble protein and SOD activity were enhanced under 8°C darkness as well however not in a sharp rise, and higher levels of MDA and GSH were recorded. The results suggested high SOD and protein levels protected cells against harsh darkness stress, while high GSH not only helped algae cells resist dark stress, but also played an important role in low temperature stress. Darkness promoted the formation of pellicle cysts of S. acuminata, and the maximum formation rates were 16.06% to 21.74% at 8°C and 20°C, respectively. Germination of pellicle cysts occurred within 24 h after light exposure, however pellicle cysts could not withstand long-time darkness stress, and all pellicle cysts died after 9-days darkness exposure. The results of this study suggest that S. acuminata is able to overcome temporary cold darkness through forming pellicle cysts.

Aim: To determine the etiology of a Chinese family with thrombocytopenia by analyzing the clinical features and genetic variation. Methods: Clinical profiles and genomic DNA extracts of the family members were collected for the study. Whole exome sequencing and Sanger sequencing was used to detect the associated genetic variation and verify the family co-segregation respectively. Bioinformatics analysis assessed the pathogenicity of missense mutations. Results: The study reported a 3-generation pedigree including eight family members with thrombocytopenia. The platelet counts of the patients were varied, ranging from 38 to 110 × 109/L (reference range: 150–450 x 109/L). The mean volumes and morphology of the sampled platelet were both normal. The bleeding abnormality and mitochondriopathy were not observed in all the patients. Clinical signs of thrombocytopenia were mild. A novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified in CYCS gene associated with autosomal dominant thrombocytopenia. Conclusion: We report the first large family with autosomal dominant non-syndromic thrombocytopenia 4 in a Chinese family, a novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified. The whole exome sequencing is an efficient tool for screening the variants specifically associated with the disease. The finding enriches the mutation spectrum of CYCS gene and laid a foundation for future studies on the correlation between genotype and phenotype.

The problem of cluster formation for agents with limited communication resources is discussed. First, we proposed the distributed dynamic event-triggered communication mechanism is raised to decrease some needless data exchanges among multi-agents. Different from some existing static event-triggered communication mechanisms (DECM). This method introduces an auxiliary parameter for each agent to dynamically adjust its threshold. Second agents in the system are break up into M nonoverlapping and different clusters. Each group of agents achieve the desired formation as far as possible, whereas the multi-agent systems accomplishes formation. Third, dynamic event-triggering mechanisms, a distributed control cluster formation protocol is proposed. Finally Simulation is used to verify the correctness of the theory.

Purpose Circular RNA (circRNA) hsa_circ_0008450 has been shown to be up-regulated in hepatocellular carcinoma (HCC). However, the functional role of hsa_circ_0008450 and its molecular mechanism are still unknown. Patients and methods We used qRT-PCR and Western blot to examine the expression levels of hsa_circ_0008450, microRNA-214-3p (miR-214-3p), and enhancer of zeste homolog 2 (EZH2) protein. CCK8 assay and wound healing assay were used to detect cell viability and cell migration capability. Cell apoptosis was assessed by flow cytometry. Luciferase reporter assay was used to explore the interaction among hsa_circ_0008450, miR-214-3p, and EZH2. Results hsa_circ_0008450 was significantly increased in HCC tissues and cells. Furthermore, knockdown of hsa_circ_0008450 in HCC cells inhibited cell proliferation, invasion, and migration. Mechanically, hsa_circ_0008450 promoted the expression of EZH2 protein through sponging miR-214-3p. Knockdown of circ_0008450 suppressed tumorigenesis of HCC cells in vivo. Conclusion Knockdown of hsa_circ_0008450 inhibits HCC progression by regulating miR-214-3p/EZH2 axis. This study suggests that hsa_circ_0008450 may serve as a novel target for the treatment of HCC.

Background: Folate and vitamin B12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. Objective: The present study aimed to determine whether supplementation with folic acid and vitamin B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. Methods: 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. Results: Compared with control group, the folic acid plus vitamin B12 group had significantly greater improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus vitamin B12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d = 0.146; P = 0.033), Information (d = 0.172; P = 0.019) and Digit Span (d = 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B12 supplementation was significantly more effective than folic acid alone for all endpoints. Conclusions: The combination of oral folic acid plus vitamin B12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B12 was significantly superior to either folic acid or vitamin B12 alone.

To explore the association between the levels of serum folate, vitamin B12, and homocysteine (Hcy), transaminase and mild cognitive impairment (MCI) in Chinese elderly. A case-control study was imp...

Sediment samples collected from 21 sites of the Pearl River networks were investigated by the sequential extraction method. Multiple environmental indices were adopted to evaluate the present and potential risks. Results indicated that concentrations of Cu, Zn, As, Cd, and Pb in most of the sedi-ments were substantially higher than their background values, and the primary sources of the contamination coming from municipal, industrial wastewater discharges and upstream mining were inferred by matrix analysis with comparing special distribution characteristics. Cd was the main factor causing the potential ecological risk in Pearl River networks. The potential mobility of heavy metals was shown in the decreasing order: Cd > Mn > Co > Zn > Ni > Cu > Pb > As > Cr.

Background: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear. Objectives: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association. Methods: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders. Results: The mean LTL was 1.56 ± 0.25 in controls, 1.44 ± 0.23 in MCI, and 1.28 ± 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101–0.597) and AD (OR 0.123; 95% CI 0.044–0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level. Conclusions: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.

Cultivable bacteria coexisting in the cultures of two microalgal species, Chattonella marina (Raphidophyceae) and Skeletonema costatum (diatom, Bacillariophyceae), which have been maintained in the laboratory for several years, were examined in this study. Forty-eight and thirty-four cultivable bacterial strains were isolated from different growth stages of C. marina and S. costatum cultures, respectively. A total of twelve unique bacterial phylotypes were isolated. These bacterial phylotypes belonged to Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and Actinobacteria. Alphaproteobacteria predominated in phycospheres of both microalgae, and Rhodobacteraceae was the most common family. Bacterial phylotypes were more diversified in cultures of S. costatum than in those of C. marina. Bacterial concentrations increased remarkably after the late stationary phase of C. marina, which might account for the decline in algal cells. One phylotype of S. costatum-associated bacteria had inhibitory effects on Chaetoceros curvisetus (Bacillariophyceae). However, most bacterial phylotypes from cultures of C. marina showed significant inhibition of the growth of C. curvisetus. The results suggested that bacteria associated with C. marina might have some ecological roles in its competition with diatoms.

Background: Nano-Se-enriched Gracilaria lemaneiformis (G. lemaneiformis) as feed ingredient on aquatic animals remained largely unknown. Feeding experiment was conducted for a total of 45 days to research the biological impacts of nano-selenium (Nano-Se) (group N), G. lemaneiformis (group G) and Nano-Se-enriched G. lemaneiformis (group NG) on growth, selenium concentration, oxidation, immunity and nutrition of Epinephelus coioides.Results: At each tested time point, the weight gain rate, specific growth rate and feed conversion rate of group N, group G and group NG were significantly increased in contrast to those of the control group (group C). A remarkable increase of the hepatosomatic index (HSI) and viscerosomatic index (VSI) was observed in group N and group NG. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of fish in group N, group G and group NG were significantly enhanced relative to those in group C. The immune system was also activated by showing an elevated expression level of various immunological genes including Immunoglobulin M, tumor necrosis factor-α and Interleukin -8. The muscle Se content in group N and group NG was 31- and 40.5-fold that of the control group (group C), respectively. The liver Se value of group N and group NG was 1.06 and 2.50 times higher than that of group C, respectively. The lipid and moisture values of group N and group NG are increased and reduced, respectively, in comparison to that of group C. The diet supplementation of Nano-Se-enriched G. lemaneiformis led to significant increase of the protein content, delicious amino acids along with total amino acids content in grouper. Conclusions: Our results demonstrate a great application potential of Nano-Se-enriched G. lemaneiformis as dietary additive in grouper.

To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia.Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene.The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 μmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149GA (p.R50H) and a maternally derived heterozygous variant c.1123GA (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123GA (p.G375S) variant. The c.149GA (p.R50H) was a known pathogenic variant, while the c.1123GA (p.G375S) variant was previously unreported.The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.

The accumulation of pyrethroid insecticides in aquatic food webs has attracted increased research attention. Fish are key species in aquatic food webs, directly connecting invertebrates and human consumption. However, little is known about the bioaccumulation of pyrethroids in wild fish species. In this study, 19 species of wild fish were collected from 11 sites in the Pearl River, China, and the levels of seven pyrethroids in the fish were determined. Linear mixed-effects models were applied to estimate the means of pyrethroid concentrations, in which sample site and fish species were set as random effects. The concentrations of Σ

Nuclear factor erythroid-2–related factor-2 (NFE2L2/Nrf2) is a transcription factor that regulates the expression of antioxidant genes. Both Kelch-like ECH-associated protein 1 (Keap1) mutations and Nrf2 mutations contribute to the activation of Nrf2 in non-small cell lung cancer (NSCLC). Nrf2 activity is associated with poor prognosis in NSCLC. Metabolic reprogramming represents a cancer hallmark. Increasing studies reveal that Nrf2 activation promotes metabolic reprogramming in cancer. In this review, we discuss the underlying mechanisms of Nrf2-mediated metabolic reprogramming and elucidate its role in NSCLC. Inhibition of Nrf2 can alter metabolic processes, thus suppress tumor growth, prevent metastasis, and increase sensitivity to chemotherapy in NSCLC. In conclusion, Nrf2 may serve as a therapeutic target for the treatment of NSCLC.

Aim To explore the clinical imaging, laboratory and genetic characteristics of a newborn boy with isolated sulfite oxidase deficiency (ISOD) in a Chinese mainland cohort. Methods Homocysteine and uric acid in plasma and cysteine and total homocysteine in the blood spot were assessed in a Chinese newborn patient with progressive encephalopathy, tonic seizures, abnormal muscle tone, and feeding difficulties. Whole exome sequencing and Sanger sequencing facilitated an accurate diagnosis. The pathogenicity predictions and conservation analysis of the identified mutations were conducted by bioinformatics tools. Results Low total homocysteine was detected in the blood spot, while homocysteine and uric acid levels were normal in the plasma. S-sulfocysteine was abnormally elevated in urine. A follow-up examination revealed several progressive neuropathological findings. Also, intermittent convulsions and axial dystonia were observed. However, the coordination of sucking and swallowing was slightly improved. A novel paternal nonsense variant c.475G > T (p.Glu159∗) and a novel maternal missense variant c.1201A > G (p.Lys401Glu) in SUOX were identified in this case by co-segregation verification. Conclusion This is the second report of early-onset ISOD case in a non-consanguineous Chinese mainland family. Combined with the clinical characteristics and biochemical indexes, we speculated that these two novel pathogenic variants of the SUOX gene underlie the cause of the disease in this patient. Next-generation sequencing (NGS) and Sanger sequencing provided reliable basis for clinical and prenatal diagnoses of this family, it also enriched the mutation spectrum of the SUOX gene.

Background Human pyruvate dehydrogenase phosphatase 1 (PDP1) plays an important physiological role in energy metabolism; however, its expression and function in human pancreatic adenocarcinoma (PDAC) remain unknown. This study aimed to investigate the expression pattern and mechanisms of action of PDP1 in human PDAC. Methods The expression pattern of PDP1 in PDAC was determined, and its correlation with patient survival was analyzed. Ectopic expression or knockdown of PDP1 was performed, and in vitro proliferation and migration, as well as in vivo tumor growth of PDAC, were measured. The mechanism was studied by biochemical approaches. Results PDP1 was overexpressed in human PDAC samples, and high expression of PDP1 correlated with poor overall and disease-free survival of PDAC patients. PDP1 promoted the proliferation, colony formation, and invasion of PDAC cells in vitro and facilitated orthotopic tumor growth in vivo. PDP1 accelerated intracellular ATP production, leading to sufficient energy to support rapid cancer progression. mTOR activation was responsible for the PDP1-induced tumor cell proliferation and invasion in PDAC. AMPK was downregulated by PDP1 overexpression, resulting in mTOR activation and cancer progression. Conclusion Our findings suggested that PDP1 could be a promising diagnostic and therapeutic target for anti-PDAC treatment.

To explore the molecular basis for a pedigree affected with coagulation factor V (FV) deficiency.Clinical data of the patient and his family members was analyzed. Targeted capture and next-generation sequencing (NGS) and Sanger sequencing were carried out to detect potential variant of the FV gene.The patient presented with jaundice and prolonged prothrombin time (PT) and activated partial thromboplastic time (APTT). V factor activity measured only 0.1% of the normal level, though the patient had no sign of bleeding. A paternal heterozygous variant c.653TC (p.F218S) and a maternal heterozygous variant c.3642_3643del (p.P1215Rfs*175) were identified in the FV gene of the patient. His elder brother was a heterozygous carrier of the c.653TC (p.F218S) variant. c.653TC(p.F218S) was a known pathogenic variant, while the c.3642_3643del (p.P1215Rfs*175) variant was unreported previously.Mutations of the FV gene probably underlie the hereditary coagulation factor V deficiency in this patient. NGS combined with Sanger sequencing has detected potential variant with efficiency and provided a reliable basis for clinical and prenatal diagnosis for this family.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide and effective therapy remains a challenge. IFIT3 is an interferon-stimulated gene with antiviral and pro-inflammatory functions. Our previous work has shown that high expression of IFIT3 is correlated with poor survival in PDAC patients who receive chemotherapy suggesting a link between IFIT3 and chemotherapy resistance in PDAC. However, the exact role and molecular mechanism of IFIT3 in chemotherapy resistance in PDAC has been unclear. Methods: A group of transcriptome datasets were downloaded and analyzed for the characterization of IFIT3 in PDAC. Highly metastatic PDAC cell line L3.6pl and patient-derived primary cell TBO368 were used and IFIT3 knockdown and the corresponding knockin cells were established for in vitro studies. Chemotherapy-induced apoptosis, ROS production, confocal immunofluorescence, subcellular fractionation, chromatin-immunoprecipitation, co-immunoprecipitation and mass spectrometry analysis were determined to further explore the biological role of IFIT3 in chemotherapy resistance of PDAC. Results: Based on PDAC transcriptome data, we show that IFIT3 expression is associated with the squamous molecular subtype of PDAC and an increase in inflammatory response and apoptosis pathways. We further identify a crucial role for IFIT3 in the regulation of mitochondria-associated apoptosis during chemotherapy. Knockdown of IFIT3 attenuates the chemotherapy resistance of PDAC cells to gemcitabine, paclitaxel, and FOLFIRINOX regimen treatments, independent of individual chemotherapy regimens. While IFIT3 overexpression was found to promote drug resistance. Co-immunoprecipitation identified a direct interaction between IFIT3 and the mitochondrial channel protein VDAC2, an important regulator of mitochondria-associated apoptosis. It was subsequently found that IFIT3 regulates the post-translational modification-O-GlcNAcylation of VDAC2 by stabilizing the interaction of VDAC2 with O-GlcNAc transferase. Increased O-GlcNAcylation of VDAC2 protected PDAC cells from chemotherapy induced apoptosis. Conclusions: These results effectively demonstrate a central mechanism by which IFIT3 expression can affect chemotherapy resistance in PDAC. Targeting IFIT3/VDAC2 may represent a novel strategy to sensitize aggressive forms of pancreatic cancer to conventional chemotherapy regimens.

A ternary mixture of diisopropyl ether, isopropanol and water exists in the production process of isopropanol. Ensuring the clean separation of this mixture is of great significance for the clean production of isopropanol from both economy and environment. However, there are three binary and one ternary minimum boiling point homogeneous azeotropes in this system, which complicate the clean production of isopropanol. In this study, with the aid of the hydration reaction of ethylene oxide, clean separation of a ternary mixture of diisopropyl ether–isopropanol–water was realized. Three separation processes—reaction–pressure swing distillation, reaction–extractive distillation and reaction–dividing wall extractive distillation—were proposed. These processes were optimized based on the sequential iterative algorithm, with the minimum total annual cost as the objective. Reaction-pressure swing distillation had the best economic performance, reaction-extractive distillation followed, and reaction-dividing wall extractive distillation performed the worst. The carbon dioxide, sulfur dioxide, and nitrogen oxide emissions of the three processes were calculated based on the optimization results. Reaction-pressure swing distillation had the lowest emissions, followed by reaction-dividing wall extractive distillation. However, reaction-extractive distillation had the highest emissions. The exergy analysis of distillation units and exchanger was performed, and the results showed that reaction-pressure swing distillation had the best exergy performance. Reaction-pressure swing distillation was better than reaction-extractive distillation and reaction-dividing wall extractive distillation in terms of economy, environment, and thermodynamic efficiency. This study provides an original idea for the clean separation of diisopropyl ether-isopropanol-water azeotropes.

An multivessel double-column pressure-swing batch distillation process and a triple-column integrated quasi-continuous distillation process were designed to separate ternary mixtures with double azeotropes of ethyl acetate-methanol-water. The process feasibility was analyzed based on ternary phase diagram. Based on a production capacity of 100 kmol/batch, the corresponding control strategy was proposed to achieve the effective separation of the mixture. Taking the minimum total annual cost as the objective function, the process parameters of the double-column process were optimized to determine the optimal operating pressure. Exergy loss of distillation column was calculated to evaluate the thermodynamic performance of the process. To further improve the separation efficiency of the process, a third column was integrated in the double-column batch distillation process to separate the methanol-water mixture directly. Combined with sequential iterative optimization sequence and multi-objective optimization algorithm, the triple-column process parameters were optimized, and the trade-off between equipment cost and carbon dioxide was realized. Thermal integration technology was adopted to further reduce the energy consumption of the triple-column process. The results show that the carbon dioxide emissions and total annual cost of the double-column process are 1.323 × 106 kg/y and 2.107 × 105 $/y. The purity of ethyl acetate and water was 99.9 mol%. While the purity of methanol was 99.5 mol%. The total annual cost and emission of the triple-column process were 1.993% and 1.890% higher than that of the double-column process, respectively, but the methanol purity was further improved to 99.9 mol%. Compared with the double-column process, the total annual cost and carbon dioxide emissions of the triple-column process with thermal integration technology were reduced by 1.281% and 17.337%.

The ammoximation of ketones is an important chemical reaction, as oximes have a wide range of industrial applications. In this study, the process of preparing methyl ethyl ketone oxime by ammoximation of methyl ethyl ketone was studied. The modeling of the reaction unit was based on the kinetic data, and the reaction conditions were analyzed. Based on the total annual cost, an economic evaluation of the process was carried out, and a sequential iterative optimization algorithm integrating the reaction conditions was used to complete the process optimization. The minimum annual total cost was 2.41 × 107 USD/yr. The exergy of methyl ethyl ketone ammoximation to methyl ethyl ketone oxime process was analyzed, and the unit with the largest exergy loss was determined. The exergy loss rate was 65% for the minimum annual total cost. Considering exergy and annual total cost as the two optimization objectives, the process was comprehensively optimized by a multi-objective optimization algorithm. The annual total cost after multi-objective optimization was 2.55 × 107 USD/yr, which is 5.8% higher than minimum total annual cost, and the exergy loss rate was 64%, which is 1.54% lower than maximum exergy-loss rate. Compared with single-objective optimization, multi-objective optimization has a better comprehensive performance.

Based on the continuous two columns distillation technology, it is difficult to separate the ternary mixture of n-hexane/ethanol/butanone, which contains three binary minimum boiling point homoazeotropes. Through analyzing characteristics of batch distillation and the phase behavior, it is feasible to achieve high purity separation of this kind of complex mixture by two-column batch distillation. Three sequential two-column batch distillation processes including Process A (Double columns with series operation), Process B (Double columns with parallel-then series operation) and Process C (Single column-then double columns process) were designed and analyzed in this work. The processes were evaluated and optimized from the aspects of economy and environment. In terms of economy, environment impacts and operating time, Process B is prior to Process A and Process C. Based on the thermodynamic analysis of the column, the heat integration problem of Process B is considered, which includes a self-preheating scheme at first step, and a heat exchange scheme in which high-pressure column top vapor provide part of the heat to low-pressure column bottom at second step. Compared with the unimproved Process B, the operating cost of the improved Process B can be reduced by 28% and TAC can be reduced by 3% at step 1. The operating cost of the improved Process B can be reduced by 30% at step 2.