The initial angle of the maximum expiratory flow-volume curve: a novel start-of-test criteria of spirometry in children.

The aim of the present study was to define an initial angle called ß and to assess its diagnostic value for identifying poor-quality maneuvers in spirometry testing in children. Furthermore, its predictive equation or normal value was explored. Children aged 4-14 years with respiratory symptoms who underwent spirometry were enrolled. Based on the efforts labeled during maneuvering and the quality control criteria of the guidelines, children were categorized into good-quality and poor-quality groups. According to ventilatory impairment, children in the good-quality group were divided into three subgroups: normal, restricted, and obstructed. Angle ß was the angle between the line from the expiratory apex to the origin of coordinates and the x-axis of the maximal expiratory flow-volume (MEFV) curve. Demographic characteristics, angle ß, and other spirometric parameters were compared among groups. The diagnostic values of angle ß, forced expiratory time (FET), and their combination were assessed using receiver operating characteristic curves. Data from 258 children in the good-quality group and 702 healthy children in our previous study were used to further explore the predictive equation or normal value of angle ß. The poor-quality group exhibited a significantly smaller angle ß (76.44° vs. 79.36°; P < 0.001), significantly lower peak expiratory flow (PEF), FET, and effective FET (ETe), and significantly higher expiratory volume at peak flow rate (FEV-PEF) and ratio of extrapolated volume and forced vital capacity (EV/FVC) than the good-quality group. There was no significant difference in angle ß among the normal, restricted, and obstructed groups. Logistic regression analysis revealed that smaller angle ß and FET values indicated poor-quality MEFV curves. The combination of angle ß < 74.58° and FET < 4.91 s had a significantly larger area under the curve than either one alone. The normal value of angle ß of children aged 4-14 years was 78.40 ± 0.12°.   Conclusions: Angle ß contributes to the quality control evaluation of spirometry in children. Both angle ß < 74.58° and FET < 4.91 s are predictors of poor-quality MEFV curves, while their combination offers the highest diagnostic value. What is Known: • A slow start is one of the leading causes of poor-quality maximal expiratory flow-volume (MEFV) curves, which is a particularly prominent issue among children due to limited cooperation, especially those younger than 6 years old. • It is relatively difficult to differentiate between ventilatory dysfunction and poor cooperation when a slow start occurs in children; therefore, there is an urgent need for an objective indicator that is unaffected by ventilatory impairment to evaluate quality control of spirometry. What is New: • The initial angle ß, which was introduced at the ascending limb of the MEFV curve in the present study, has a certain diagnostic value for poor-quality MEFV curves in children. • Angle ß < 74.58° is a predictor of poor-quality MEFV curves, and its combination with FET < 4.91 s offers a higher diagnostic value.

CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2.

BACKGROUND: circular RNAs (circRNAs) have been reported to play crucial roles in the biology of different cancers. However, little is known about the function of circSTX6 (hsa_circ_0007905) in pancreatic ductal adenocarcinoma (PDAC). METHODS: circSTX6, a circRNA containing exons 4, 5, 6 and 7 of the STX6 gene, was identified by RNA sequencing and detected by quantitative reverse transcription PCR (qRT-PCR). The biological function of circSTX6 was assessed in vitro and in vivo. The relationship between circSTX6 and miR-449b-5p was confirmed by biotin-coupled circRNA capture, fluorescence in situ hybridization (FISH) and luciferase reporter assays. The interaction of circSTX6 with Cullin 2 (CUL2) was verified by RNA-protein RNA pull-down, RNA immunoprecipitation (RIP) and western blotting assays. RESULTS: circSTX6 was frequently upregulated in PDAC tissues, and circSTX6 overexpression promoted tumor proliferation and metastasis both in vitro and in vivo. Furthermore, circSTX6 expression was associated with tumor differentiation and N stage. Mechanistically, circSTX6 regulated the expression of non-muscle myosin heavy chain 9 (MYH9) by sponging miR-449b-5p. Moreover, circSTX6 was confirmed to participate in the ubiquitin-dependent degradation of hypoxia-inducible factor 1-alpha (HIF1A) by interacting with CUL2 and subsequently accelerating the transcription of MYH9. CONCLUSIONS: Our findings indicate that circSTX6 facilitates proliferation and metastasis of PDAC cells by regulating the expression of MYH9 through the circSTX6/miR-449b-5p axis and circSTX6/CUL2/HIF1A signaling pathway. Therefore, circSTX6 could serve as a potential therapeutic target for the treatment of PDAC.

CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing.

BACKGROUND: A growing number of studies have focused on investigating circRNAs as crucial regulators in the progression of multiple cancer types. Nevertheless, the biological effects and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unclear. METHODS: Differentially expressed circRNAs between cancerous tissue and adjacent normal tissues were identified by RNA sequencing in PDAC. Subsequently, in vitro and in vivo functional experiments were performed to investigate the functional roles of circNEIL3 in PDAC tumour growth and metastasis. Furthermore, RNA pull-down, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH) and Sanger sequencing assays were performed to examine the circular interaction among circNEIL3, miR-432-5p and adenosine deaminases acting on RNA 1 (ADAR1). RESULTS: CircNEIL3 was upregulated in PDAC and promoted the progression of PDAC cells both in vitro and in vivo. Mechanistically, circNEIL3 was shown to regulate the expression of ADAR1 by sponging miR-432-5p to induce RNA editing of glioma-associated oncogene 1 (GLI1), ultimately influencing cell cycle progression and promoting epithelial-to-mesenchymal transition (EMT) in PDAC cells. Moreover, we discovered that the circNEIL3/miR-432-5p/ADAR1 axis was correlated with the PDAC clinical stage and overall survival of PDAC patients, while ADAR1 may reduce the biogenesis of circNEIL3. CONCLUSIONS: Our findings reveal that circNEIL3 facilitates the proliferation and metastasis of PDAC through the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is regulated by ADAR1 through a negative feedback loop. Therefore, circNEIL3 may serve as a prognostic marker and a therapeutic target for PDAC.

Long noncoding RNA SOX2OT promotes the proliferation of pancreatic cancer by binding to FUS.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors has one of the worst prognoses, and the role of long noncoding RNAs (lncRNAs) in the biological and pathological processes of pancreatic cancer, including tumor cell proliferation, is a popular topic in tumor research. Our previous study revealed the correlation between high levels of the lncRNA-SOX2OT (SOX2OT) with poor survival outcomes. Cell Counting Kit-8, EdU, Flow cytometry and Colony formation assays as well as Xenograft growth of PDAC cells in mice were used for the detection of PDAC cells proliferation progression. Fluorescence in situ hybridization, RNA-binding protein pulldown and RNA immunoprecipitation assays were also used to identify the putative mechanisms of SOX2OT participating in the tumor progression. SOX2OT and its potential downstream targets were verified by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). SOX2OT was confirmed to promote the proliferation of PDAC cells. It was found to directly physically bind to FUS and we also demonstrated that FUS protein stability was affected by binding with SOX2OT and FUS could suppressed PDAC tumor by regulating cell cycle-associated factors CCND1 and p27. Our findings suggest that SOX2OT may act as a tumor promoter in PDAC through physically binding FUS and regulating its downstream cell cycle-associated factors CCND1 and p27. It may serve as an effective target for antitumor treatment for pancreatic cancer.

YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways.

BACKGROUND: Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated. METHODS: In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer. RESULTS: Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways. CONCLUSION: Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.

A DFT + U study of acetylene selective hydrogenation over anatase supported PdaAgb (a + b = 4) cluster.

It is well known that the addition of Ag into Pd can promote the selectivity of acetylene hydrogenation to ethylene, and early theoretical studies focus on ideal single crystal model catalysts, so it is worth studying relatively realistic catalyst models, such as metal oxide supported PdAg systems. In this work, the reaction mechanisms for acetylene selective hydrogenation on the anatase TiO2(101) supported PdaAgb (a + b = 4) cluster are studied by density functional theory calculations with a Hubbard U correction. The results show that Ag addition to the Pd4 cluster reduces the interaction between the PdAg cluster and the support, and the possible reason is that the amount of electron transfer from the TiO2 support to the PdAg cluster decreases with increasing number of Ag atoms. Consequently the adsorption energies of acetylene and ethylene would become smaller on the anatase supported PdAg cluster as compared to that on the anatase supported Pd4 cluster, and this may help to enhance the selectivity of ethylene formation. Moreover, the reaction kinetics study of acetylene hydrogenation on anatase TiO2(101) supported PdAg cluster shows that the activation energy of the hydrogenation step is higher on the PdAg cluster than that on the pure Pd4 cluster, and thus reduces its catalytic activity. Importantly, the present calculation results suggested that the selectivity of ethylene formation, which is defined as the energy difference between the adsorption energy of ethylene and the barrier for its further hydrogenation, varies with the ratio of Pd/Ag in the PdAg cluster: the Pd3Ag system shows relatively low selectivity compared to that of the pure Pd4 cluster, whereas Pd2Ag2/PdAg3 displays higher selectivity than that of the pure Pd4 cluster. Furthermore, our present results demonstrated that the anatase support plays a key role in the acetylene hydrogenation processes: on one hand, it reduces the reaction activity of acetylene hydrogenation processes compared to the Pd2Ag2/Pd(111) and Pd2Ag2 clusters; on the other hand, it enhances the selectivity of ethylene due to its lower desorption energy. It was also found that the carbon species inside the Pd2Ag2 cluster has little effect on the catalytic selectivity towards ethylene formation, whereas the hydrogenation catalytic activity is enhanced significantly. Finally the role of the Pd2Ag2-anatase interface on the catalytic properties of acetylene hydrogenation was studied, and it was found that the interface can increase the activity of acetylene hydrogenation but the selectivity is not improved.

Effects of different concentrations of biochar amendments and Pb toxicity on rhizosphere soil characteristics and bacterial community of red clover (Trifolium pretense L.).

Amending soil with biochar can reduce the toxic effects of heavy metals (HM) on plants and the soil. However, the effects of different concentrations of biochar on the properties and microbial activities in lead (Pb)-contaminated soils are unclear. In this study, two Pb concentrations were set (low, 1000 mg/kg; high, 5000 mg/kg), and five corn straw biochar (CSB) concentrations (0, 2.5, 5, 10 and 15%) were used to determine the response of the growth and rhizosphere of red clover (Trifolium pretense L.) (in terms of soil properties and bacteria) to CSB and Pb application. The results showed that 5% CSB better alleviated the toxicity of Pb on the shoot length of red clover, the biomass increased by 74.55 and 197.76% respectively and reduced the enrichment factor (BCF) and transport factor (TF) of red clover. Pb toxicity reduced soil nutrients, catalase (CAT), acid phosphatase (ACP) and urease activity, while the addition of CSB increased soil pH, soil organic matter (SOM) content and soil enzyme activity. 16S rDNA amplicon sequencing analysis showed that Pb toxicity reduced the diversity of rhizosphere bacteria in red clover and reduced the relative abundance of plant growth-promoting rhizobacteria such as Gemmatimonas, Devosia and Bryobacter. Spearman correlation analysis showed that the addition of alkaline CSB restored the relative abundance of rhizobacteria positively correlated with pH, such as Chitinophaga, Sphingomonas, Devosia and Pseudomonas, and thus restored the rhizosphere soil environment. This study demonstrates that 5% CSB can better alleviate the toxicity of Pb to red clover and soil. We also provide a theoretical basis for the subsequent use of beneficial bacteria to regulate the repair efficiency of red clover.

The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer.

Background: Pancreatic cancer (PC) is a malignant cancer with poor prognosis and high mortality rate. Sine oculis homeobox homolog 1 (SIX1) participates in the development of many cancers. However, the function of SIX1 in PC is not fully understood. Methods: SIX1 expression was determined using immunohistochemistry in PC tissues and cell lines. Glucose consumption, lactate production, and ATP assays were used to detect the function of SIX1. PC cells and NK cells were cocultured to study the effect of SIX1 overexpression in PC cells on NK cell function. Chromatin immunoprecipitation (ChIP) assays were used to study the relationship between SIX1 and lactate dehydrogenase A (LDHA). A series of in vitro and in vivo assays were further applied to elucidate the important role of the SIX1/LDHA axis in metabolism and NK cell dysfunction in PC. Results: SIX1 was significantly upregulated in PC tissue; SIX1 overexpression promoted the glycolysis capacity of PANC-1 and CFPAC-1 cells and resulted in NK cell dysfunction after the NK cells had been cultured with PC cells. LDHA inhibitor partially restored the promotion of PC caused by SIX1 overexpression. According to ChIP assays, SIX1 directly binds to the LDHA promoter region. Moreover, LDHA inhibitor and lactate transporter blocker treatment promoted the function of NK cells cocultured with PC cells. In vivo experiments yielded the same results. Conclusion: The SIX1/LDHA axis promotes lactate accumulation and leads to NK cell dysfunction in PC.

[Effects of yijing recipe on sperm apoptosis and mitochondrial membrane potential in patients with idiopathic oligoathenoteratospermia].

OBJECTIVE: To investigate the effects of Yijing Recipe on sperm apoptosis and mitochondrial membrane potential (MMP) in patients with idiopathic oligoathenoteratospermia. METHODS: Using the self-control method, we examined sperm apoptosis and MMP in 30 patients with oligoathenoteratospermia before and after treated with Yijing Recipe. RESULTS: The rates of early sperm apoptosis (AV +/PI -) and MMP loss were significantly reduced after treatment as compared with pre-medication ([2.86 +/- 1.47]% vs [4.26 +/- 2.79]% and [21.77 +/- 13.46]% vs [41.73 +/- 20.30]%, P<0.05). No statistically significant difference was observed in the sperm death rate (PI+) before and after treatment ([34.10 +/- 16.26]% vs [30.21 +/- 13.50]%, P>0.05). CONCLUSION: Yijing Recipe can reduce early sperm apoptosis and improve MMP, which may be one of the mechanisms underlying its efficacy on oligoathenoteratospermia.

Integrated physiological, transcriptomic and metabolomic analysis of the response of Trifolium pratense L. to Pb toxicity.

Lead (Pb) interferes with plant gene expression, alters metabolite contents and affects plant growth. However, the molecular mechanism underlying the plant response to Pb is not completely understood. In the present study, Trifolium pratense L. was exposed to Pb concentrations of 0 (Pb0), 500 (Pb500), 1000 (Pb1000), 2000 (Pb2000) and 3000 (Pb3000) mg/kg in soils. Pb stress affected the ability of T. pratense to accumulate and transport Pb, increased the activity of peroxidase (POD) and the contents of malondialdehyde (MDA) and proline, decreased the amount of photosynthetic pigments and soluble proteins, and led to changes in growth and biomass. Transcriptomic and metabolomic analyses showed that Pb mainly affected eight pathways, and LHC, flavonoids, organic acids, amino acids and carbohydrates were upregulated or downregulated. Moreover, Pb500 induced the upregulation of serA, promoted the synthesis of citric acid, maintained photosynthetic pigment levels, and ultimately promoted an increase in stem length. Pb3000 induced the upregulation of ARF, GH3 and SAUR genes, but the saccharide contents and stem length decreased in response to Pb stress. We used a variety of methods to provide a molecular perspective on the mechanism underlying the response of T. pratense to Pb stress.

The Caucasian Clover Gene TaMYC2 Responds to Abiotic Stress and Improves Tolerance by Increasing the Activity of Antioxidant Enzymes.

Abiotic stress affects metabolic processes in plants and restricts plant growth and development. In this experiment, Caucasian clover (Trifolium ambiguum M. Bieb.) was used as a material, and the CDS of TaMYC2, which is involved in regulating the response to abiotic stress, was cloned. The CDS of TaMYC2 was 726 bp in length and encoded 241 amino acids. The protein encoded by TaMYC2 was determined to be unstable, be highly hydrophilic, and contain 23 phosphorylation sites. Subcellular localization results showed that TaMYC2 was localized in the nucleus. TaMYC2 responded to salt, alkali, cold, and drought stress and could be induced by IAA, GA3, and MeJA. By analyzing the gene expression and antioxidant enzyme activity in plants before and after stress, we found that drought and cold stress could induce the expression of TaMYC2 and increase the antioxidant enzyme activity. TaMYC2 could also induce the expression of ROS scavenging-related and stress-responsive genes and increase the activity of antioxidant enzymes, thus improving the ability of plants to resist stress. The results of this experiment provide references for subsequent in-depth exploration of both the function of TaMYC2 in and the molecular mechanism underlying the resistance of Caucasian clover.

Identification and responding to exogenous hormone of HB-KNOX family based on transcriptome data of Caucasian clover.

Caucasian clover (Trifolium ambiguum M. Bieb.) is a strongly rhizomatous, low-crowned perennial leguminous and ground-covering grass. The species is resistant to cold, arid temperatures and grazing due to a well-developed underground rhizome system and a strong clonal reproduction capacity. KNOTTED1-LIKE HOMEOBOX (KNOX) genes are a family of plant-specific homeobox transcription factors with important roles in plant development. Preliminary transcriptome analysis enabled us to understand the gene expression in five different tissues, which helped us to screen the predetermined genes of the HB-KNOX family genes for the rhizome growth and development of Caucasian clover. The study identified 41 TaKNOX genes from the Caucasian clover transcriptome database. Gene length, MW and pl of TaKNOX family transcription factors varied, but the gene structure and motifs were relatively conserved in bioinformatics analysis. Phylogenetic analyses of Arabidopsis thaliana, soybean, Medicago truncatula and Caucasian clover were performed to study the evolutionary and functional relationships in various species. Prediction and verification of the subcellular localizations revealed the diverse subcellular localization of these 41 TaKNOX proteins. The expression profile of exogenous hormones showed that the TaKNOX gene showed multiple expression regulation patterns, and was involved in 6-BA, IAA and KT signaling pathways. Our results reveal the characteristics of the TaKNOX gene family, thus laying a foundation for further functional analysis of the KNOX family in Caucasian clover.

Cloning of TaeRF1 gene from Caucasian clover and its functional analysis responding to low-temperature stress.

Low temperature (LT) is an important threat to the normal growth of plants. In this study, based on the full-length transcriptome sequencing results, the cold resistance genes were cloned from Caucasian clover with strong cold resistance. We cloned the CDS of TaeRF1, which is 1311 bp in length and encodes 436 amino acids. The molecular weight of the protein is 48.97 kDa, which had no transmembrane structure, and its isoelectric point (pI) was 5.42. We predicted the structure of TaeRF1 and found 29 phosphorylation sites. Subcellular localization showed that TaeRF1 was localized and expressed in cell membrane and chloroplasts. The TaeRF1 gene was induced by stress due to cold, salt, alkali and drought and its expression level was higher in roots and it was more sensitive to LT. Analysis of transgenic A. thaliana plants before and after LT treatment showed that the TaeRF1 gene enhanced the removal of excess H2O2, and increased the activity of antioxidant enzymes, thus improving the plant's ability to resist stress. Additionally, the OE lines showed increased cold tolerance by upregulating the transcription level of cold-responsive genes (CBF1, CBF2, COR15B, COR47, ICE1, and RD29A). This study demonstrates that TaeRF1 is actively involved in the responses of plants to LT stress. We also provide a theoretical basis for breeding and a potential mechanism underlying the responses of Caucasian clover to abiotic stress.

Laparoscopic treatment for an intrapancreatic accessory spleen: A case report.

Malignant pancreatic tumors have early metastasis, aggressive behavior and poor prognosis. Surgeons often need to judge whether a patient needs prompt surgery when a pancreatic lesion is found. The accessory spleen is a congenital developmental malformation rather than a tumor and does not require surgical resection. Here, we report a 47-year-old man who underwent routine gastroscopic examination, and a submucosal eminence of the duodenal bulb was detected. The patient was asymptomatic and laboratory tests were unremarkable. Duodenal neuroendocrine neoplasm (G2) was considered following endoscopic submucosal dissection (ESD). Further examination showed a lesion in the tail of the pancreas and multiple accessory spleens. The lesion in the tail of the pancreas was Ga-68 positive and was highly considered a pancreatic neuroendocrine tumor (pNET). Based on this clinical evidence, laparoscopic spleen-preserving distal pancreatectomy (Kimura) was performed. However, the results of the postoperative pathological diagnosis indicated an intrapancreatic accessory spleen (IPAS). Given the findings of this case, we should explore more accurate diagnostic methods for IPAS to avoid unnecessary surgery.

Suppressive effect of YY1-mediated RGS22 regulation on the proliferation, migration and invasion of pancreatic ductal adenocarcinoma.

Regulator of G-protein signaling 22 (RGS22) is specifically expressed in the testis and in tumors of epithelial origin, but the expression and role of RGS22 in pancreatic cancer are unclear. In this study, 52 pairs of pancreatic ductal adenocarcinoma (PDAC) and adjacent non-neoplastic tissue samples with the corresponding clinical data were used to examine the expression of RGS22 and its relationship with PDAC prognosis. The findings showed that the expression of RGS22 was higher in the PDAC tissues than in the adjacent non-tumorous tissues and its expression was associated with the degree of blood vessel invasion. The in vitro experiments with PDAC cell lines and a normal control cell line showed that the proliferation, invasion, and metastasis of PDAC cells were suppressed by RGS22 overexpression and enhanced by RGS22 knockdown. The in vivo effect of RGS22 on PDAC xenografts was studied using subcutaneous implantation of tumor cells in BALB/cA-nu mice, and the results corroborated the in vitro findings. Analysis of the regulators of RGS22 showed that it was positively regulated by the transcription factor Yin Yang-1 (YY1). Thus, YY1-mediated RGS22 regulation suppressed the proliferation, migration, and invasion of PDAC.

Selective use of pancreatic duct occlusion during pancreaticoduodenectomy in patients with a small-size duct and atrophic parenchyma in the distal pancreas: A retrospective study.

Background: Despite the advancements in surgical techniques, postoperative pancreatic fistula (POPF) remains a potentially life-threatening complication of pancreaticoduodenectomy (PD). Pancreatic duct occlusion (PDO) without anastomosis has also been proposed to alleviate the clinical consequences of POPF in selected patients after PD. Objectives: To assess the safety and effectiveness of PDO with mechanical closure after PD in patients with an atrophic pancreatic body-tail and a small pancreatic duct. Methods: We retrospectively identified two female and two male patients from April 2019 to October 2020 through preoperative computed tomography of the abdomen. Among them, three patients underwent PDO with mechanical closure after PD, and one underwent PDO after pylorus-preserving PD. In addition, patients' medical records and medium-and long-term follow-up data were analyzed. Results: Postoperative histological examination revealed a solid pseudopapillary tumor in two patients, pancreatic ductal adenocarcinoma in one patient, and chronic pancreatitis with pancreatic duct stones in one patient. However, none of the patients developed biochemical or clinically relevant POPF, with no postpancreatectomy hemorrhage, biliary leakage, delayed gastric emptying, intra-abdominal abscess, or chyle leakage. Among the four patients, three developed new-onset diabetes mellitus, and one had impaired glucose tolerance. Furthermore, three patients received pancreatic enzyme supplementation at a dose of 90,000 Ph. Eur. units/d, and one was prescribed a higher dose of 120,000 Ph. Eur. units/d. Conclusions: PDO with mechanical closure is an alternative approach for patients with an atrophic pancreatic body-tail and a small pancreatic duct after PD. Therefore, further evidence should evaluate the potential benefits of selective PDO in these patients.

Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice.

Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.

Transcriptome profiling unveils the mechanism of phenylpropane biosynthesis in rhizome development of Caucasian clover.

Caucasian clover is the only perennial herb of the genus Leguminous clover with underground rhizomes. However, we know very little about its development process and mechanism. Transcriptome studies were conducted on the roots of Caucasian clover without a rhizome (NR) at the young seedling stage and the fully developed rhizome, including the root neck (R1), main root (R2), horizontal root (R3), and rhizome bud (R4), of the tissues in the mature phase. Compared with the rhizome in the mature phase, NR had 893 upregulated differentially expressed genes (DEGs), most of which were enriched in 'phenylpropanoid biosynthesis', 'phenylalanine metabolism', 'DNA replication' and 'biosynthesis of amino acids'. A higher number of transcription factors (AP2/ERF, C2H2 and FAR1) were found in NR. There were highly expressed genes for R4, such as auxin response factor SAUR, galacturonosyltransferase (GAUT), and sucrose synthase (SUS). Phenylpropanoids are very important for the entire process of rhizome development. We drew a cluster heat map of genes related to the phenylpropanoid biosynthesis pathway, in which the largest number of genes belonged to COMT, and most of them were upregulated in R4.

FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma.

BACKGROUND: Circular RNAs (circRNAs) are becoming a unique member of non-coding RNAs (ncRNAs) with emerging evidence of their regulatory roles in various cancers. However, with regards to pancreatic ductal adenocarcinoma (PDAC), circRNAs biological functions remain largely unknown and worth investigation for potential therapeutic innovation. METHODS: In our previous study, next-generation sequencing was used to identify differentially expressed circRNAs in 3 pairs of PDAC and adjacent normal tissues. Further validation of circRHOBTB3 expression in PDAC tissues and cell lines and gain-and-loss function experiments verified the oncogenic role of circRHOBTB3. The mechanism of circRHOBTB3 regulatory role was validated by pull-down assays, RIP, luciferase reporter assays. The autophagy response of PANC-1 and MiaPaca-2 cells were detected by mCherry-GFP-LC3B labeling and confocal microscopy, transmission electron microscopy and protein levels of LC3B or p62 via Western blot. RESULTS: circRHOBTB3 is highly expressed in PDAC cell lines and tissues, which also promotes PDAC autophagy and then progression in vitro and in vivo. Mechanistically, circRHOBTB3 directly binds to miR-600 and subsequently acts as a miRNA-sponge to maintain the expression level of miR-600-targeted gene NACC1, which facilitates the autophagy response of PDAC cells for adaptation of proliferation via Akt/mTOR pathway. Moreover, the RNA-binding protein FUS (FUS) directly binds to pre-RHOBTB3 mRNA to mediate the biogenesis of circRHOBTB3. Clinically, circRHOBTB3, miR-600 and NACC1 expression levels are correlated with the prognosis of PDAC patients and serve as independent risk factors for PDAC patients. CONCLUSIONS: FUS-mediated circRHOBTB3 functions as a tumor activator to promote PDAC cell proliferation by modulating miR-600/NACC1/Akt/mTOR axis regulated autophagy.