Comprehensively dissecting the hub regulation of PkaC on high-productivity and pellet macromorphology in citric acid producing Aspergillus niger.

Aspergillus niger, an important industrial workhorse for citric acid production, is characterized by polar hyphal growth with complex pelleted, clumped or dispersed macromorphologies in submerged culture. Although organic acid titres are dramatically impacted by these growth types, studies that assess productivity and macromorphological changes are limited. Herein, we functionally analysed the role of the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) signalling cascade during fermentation by disrupting and conditionally expressing the pkaC gene. pkaC played multiple roles during hyphal, colony and conidiophore growth. By overexpressing pkaC, we could concomitantly modify hyphal growth at the pellet surface and improve citric acid titres up to 1.87-fold. By quantitatively analysing hundreds of pellets during pilot fermentation experiments, we provide the first comprehensive correlation between A. niger pellet surface morphology and citric acid production. Finally, by intracellular metabolomics analysis and weighted gene coexpression network analysis (WGCNA) following titration of pkaC expression, we unveil the metabolomic and transcriptomic basis underpin hyperproductivity and pellet growth. Taken together, this study confirms pkaC as hub regulator linking submerged macromorphology and citric acid production and provides high-priority genetic leads for future strain engineering programmes.

Phosphorylation of islet-1 serine 269 by CDK1 increases its transcriptional activity and promotes cell proliferation in gastric cancer.

BACKGROUND: Despite recent advances in diagnostic and therapeutic approaches for gastric cancer (GC), the survival of patients with advanced GC remains very low. Islet-1 (ISL1) is a LIM-homeodomain transcription factor, which is upregulated and promotes cell proliferation in GC. The exact mechanism by which ISL1 influences GC development is unclear. METHODS: Co-immunoprecipitation (co-IP) and glutathione S-transferase (GST)-pulldown assays were employed to evaluate the interaction of ISL1 with CDK1. Western blot and immunohistochemistry analyses were performed to evaluate the ability of CDK1 to phosphorylate ISL1 at Ser 269 in GC cell and tissue specimens. Chromatin immunoprecipitation (ChIP), ChIP re-IP, luciferase reporter, and CCK-8 assays were combined with flow cytometry cell cycle analysis to detect the transactivation potency of ISL1-S269-p and its ability to promote cell proliferation. The self-stability and interaction with CDK1 of ISL1-S269-p were also determined. RESULTS: ISL1 is phosphorylated by CDK1 at serine 269 (S269) in vivo. Phosphorylation of ISL1 by CDK1 on serine 269 strengthened its binding on the cyclin B1 and cyclin B2 promoters and increased its transcriptional activity in GC. Furthermore, CDK1-dependent phosphorylation of ISL1 correlated positively with ISL1 protein self-stability in NIH3T3 cells. CONCLUSIONS: ISL1-S269-p increased ISL1 transcriptional activity and self-stability while binding to the cyclinB1 and cyclinB2 promoters promotes cell proliferation. ISL1-S269-p is therefore crucial for tumorigenesis and potentially a direct therapeutic target for GC.

Investigation on a cluster of overseas imported COVID-19 in Qingtian County / 预防医学

Objective@#To conduct an epidemiological investigation on a cluster of overseas imported cases of coronavirus disease 2019(COVID-19)in Qingtian County, Lishui,so as to provide reference for the prevention and control of COVID-19 imported from abroad. @*Methods@#According to the COVID-19 Prevention and Control Program (FiFth Edition) issued by National Health Commission of China,a field investigation was employed and the close contacts of the case were tracked down ;the real-time reverse transcription polymerase chain reaction (RT-PCR) assay was performed to detect the nucleic acid of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the sputum specimens or throat swabs of cases;the epidemiological characteristics,source of infection,route of transmission and disposal of the cluster were analyzed. @*Results@#From March 1 to March 6,2020,eight confirmed cases and one asymptomatic case of COVID-19 were reported. Their median age was 33 years old. The nine cases all had no fever,no decrease in leukocyte and lymphocyte levels,and the clinical symptoms of seven cases were not obvious. The asymptomatic case had been tested negative for SARS-CoV-2 for six times,but had been weakly positive for IgM antibody and strongly positive for IgG antibody. Nine cases were all the employees of the same restaurant in Begamo,Italy. They lived in three independent villas and usually had lunch and dinner in the restaurant where they worked. Begamo had COVID-19 epidemic,but the staff of the restaurant did not take any protective measures such as wearing masks and environmental disinfection. Eight cases reported to have cold symptoms in Italy during mid February. Through a closed-loop management of“all people,all sites,all chains ”,such as treatment of current cases,screening and isolation of close contacts and health education,totally 372 close contacts were traced back,yet no fever or respiratory symptoms have been found. @*Conclusions @# It was a cluster of COVID-19 cases imported from abroad. The clinical symptoms of the cases were not obvious. Qingtian County adopted the closed-loop management in time,and effectively controlled the spread of the epidemic. No second-generation cases have been found.

Effect of cognitive behavior therapy combined with exercise intervention on the cognitive bias and coping styles of diarrhea-predominant irritable bowel syndrome patients.

BACKGROUND: Irritable bowel syndrome (IBS) is a common digestive system disease with a high incidence rate and is common in women. The cause of IBS remains unclear. Some studies have shown that mental and psychological diseases are independent risk factors for IBS. At present, the treatment of IBS is mainly symptomatic treatment. Clinically, doctors also use cognitive behavioral therapy to improve patients' cognitive ability to diseases and clinical symptoms. In recent years, exercise therapy has attracted more and more attention from scholars. Improving the symptoms of IBS patients through psychosomatic treatment strategy may be a good treatment method. AIM: To explore the effects of an intervention of cognitive behavioral therapy combined with exercise (CBT+E) on the cognitive bias and coping styles of patients with diarrhea-predominant irritable bowel syndrome (IBS-D); and to provide a theoretical reference for the management of IBS. METHODS: Sixty IBS-D patients and thirty healthy subjects were selected. The 60 IBS-D patients were randomly divided into experimental and control groups. The experimental group was treated with the CBT+E intervention, while the control group was treated with conventional drugs without any additional intervention. The cognitive bias and coping styles of the participants were evaluated at baseline and after 6 wk, 12 wk and 24 wk using the Automatic Thoughts Questionnaire (ATQ), Dysfunctional Attitudes Scale (DAS) and Pain Coping Style Questionnaire (CSQ) instruments, and the intervention effect was analyzed using SPSS 17.0 statistical software. RESULTS: At baseline, the scores on the various scales showed that all subjects had cognitive bias and adverse coping styles. The IBS Symptom Severity Scale (IBS-SSS) scores, ATQ total scores, DAS scores and CSQ scores of the two groups were not significantly different (P > 0.05). Compared with baseline, after 6 wk of the CBT+E intervention, there were significant differences in the ATQ scores, the dependence and total scores on the DAS, and the catastrophization, distraction and prayer scores on the CSQ (P < 0.05). After 12 wk, there were significant differences in the scores for perfectionism on the DAS and in the scores for reinterpretation, neglect and pain behavior on the CSQ in the experimental group (P < 0.05). After 24 wk, there were significant differences in the vulnerability, dependence, perfectionism, and total scores on the DAS and in the catastrophization, distraction and prayer scores on the CSQ in the experimental group (P < 0.01). The IBS-SSS scores were negatively correlated with the ATQ and DAS total scores (P < 0.05) but were positively correlated with the CSQ total score (P < 0.05). CONCLUSION: Intervention consisting of CBT+E can correct the cognitive bias of IBS-D patients and eliminate their adverse coping conditions. CBT+E should be promoted for IBS and psychosomatic diseases.

[Diagnosis of an imported falciparum malaria case by fluorescence quantitative PCR].

The whole blood sample from a patient with imported falciparum malaria was tested by microscopic examination and fluorescence quantitative PCR. Microscopic examination results showed that Plasmodium falciparum parasites were found in the thick and thin blood films with a low parasite density of 240 parasite/microl of blood. The specific DNA fragment of P. falciparum was amplified by fluorescence quantitative PCR, and this case was further confirmed as P. falciparum infection.

Study about the effects of different fitness sports on cognitive function and emotion of the aged.

The aim of the study was to explore the effects of different fitness sports on cognitive function and emotion of the aged people. A total of 150 subjects aged between 60 and 70 were recruited from Shenyang Aged University and elderly activity center. All subjects reported no fitness before this study. The aged subjects were divided into five groups, included swimming group (A group), running group (B group), square dancing group (C group), Tai Chi group (D group) and control group (E group) with 30 people in each group. Subjects in each group received exercise intervention continued for 18 months. At baseline, 6, 12 and 18 months after intervention, the P300 test, SECF, HAMD and HAMA scale evaluations were performed. Compared to E group, the P2, N2 and P3 latency and response time in the D group after intervention for 6 months, and in the A-C groups after intervention for 12 months were significantly prolonged. The anxiety symptom and depression levels in the A-D groups after intervention for 12 months were significantly decreased when compared to E group (P < 0. 01), where significantly improved compared with the E group (P < 0. 01). The effect of exercise intervention for Tai Chi group was the most significant. Different fitness sports have marked beneficial effect on cognitive function and emotion of the aged people, especially the Tai Chi exercise.