Tetraacetyl phytosphingosine (TAPS) is an excellent raw material for natural skin care products. Its deacetylation leads to the production of phytosphingosine, which can be further used for synthesizing the moisturizing skin care product ceramide. For this reason, TAPS is widely used in the skin care oriented cosmetics industry. The unconventional yeast Wickerhamomyces ciferrii is the only known microorganism that can naturally secrete TAPS, and it has become the host for the industrial production of TAPS. This review firstly introduces the discovery, functions of TAPS, and the metabolic pathway for TAPS biosynthesis is further introduced. Subsequently, the strategies for increasing the TAPS yield of W. ciferrii, including haploid screening, mutagenesis breeding and metabolic engineering, are summarized. In addition, the prospects of TAPS biomanufacturing by W. ciferrii are discussed in light of the current progresses, challenges, and trends in this field. Finally, guidelines for engineering W. ciferrii cell factory using synthetic biology tools for TAPS production are also presented.
Sphingosine ; Ceramides ; Metabolic Engineering ; Synthetic Biology

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Objective:To explore the clinical value of N terminal pro B type natriuretic peptide (NT-proBNP) in diagnosing or predicting heart failure in peridialysis chronic kidney disease (CKD) population.Methods:It was a single-center retrospective study. Patients with peridialysis CKD who visited the Department of Nephrology, First Affiliated Hospital of Zhengzhou University from January 2021 to June 2021 were collected and divided into 4 groups according to the presence or absence of heart failure and the level of left ventricular ejection fraction (LVEF), namely the non-heart failure group, heart failure with reduced ejection fraction (HFrEF) group (LVEF<40%), heart failure with mid-range ejection fraction (HFmrEF) group (40％≤LVEF<50％), and heart failure with preserved ejection fraction (HFpEF) group (LVEF≥50％). The NT-proBNP, echocardiography and other indicators of the 4 groups were compared. The value of plasma NT-proBNP in diagnosing heart failure, HFpEF, HFmrEF and HFrEF was analyzed by drawing receiver operating characteristic curve (ROC curve). Logistic regression analysis was used to analyze the related factors of heart failure in peridialysis CKD patients.Results:A total of 508 patients were included, including 11 cases in the HFrEF group, 29 cases in the HFmrEF group, 152 cases in the HFpEF group, and 316 cases without heart failure. The differences in age, 24-h urine volume, hemodialysis proportion, non-dialysis proportion, serum creatinine, estimated glomerular filtration rate, hemoglobin, serum albumin, C-reactive protein, NT-proBNP, cardiac troponin I, left ventricular internal diameter, LVEF, pulmonary artery systolic pressure, left ventricular end-diastolic volume, E/A value, septal thickness, and left ventricular posterior wall thickness among the four groups were statistically significant ( P < 0.05, respectively). A two-pair comparison (all P values corrected by Bonferroni method) revealed that the 24-h urine volume was higher in the non-heart failure group than in the other three groups (corrected P<0.05, respectively), while the proportion of hemodialysis patients and the levels of NT-proBNP and C-reactive protein were lower in the non-heart failure group than in the other three groups (corrected P<0.001, respectively); the levels of hemoglobin and serum albumin were lower in the HFpEF group than in the non-heart failure group (corrected P<0.001, respectively); troponin I was lower in the non-heart failure group than in the HFpEF group (corrected P<0.001), HFmrEF group (corrected P=0.001) and HFrEF group (corrected P<0.001), and troponin I was lower in the HFpEF group than in the HFrEF group (corrected P=0.008); LVEF was higher in the non-heart failure group than in the other three groups (corrected P<0.001, respectively), and LVEF in the HFpEF group was higher than in the HFmrEF and HFrEF groups (corrected P<0.001, respectively). For patients with peridialysis CKD, the cut-off values of plasma NT-proBNP for diagnosing or predicting heart failure, HFpEF, HFmrEF and HFrEF were 4 943.33 ng/L, 4 976.83 ng/L, 14 964.5 ng/L and 17 847.55 ng/L, respectively. Multivariate logistic regression analysis showed that NT-proBNP (every 500 ng/L increase, OR=1.390, 95% CI 1.287-1.501, P<0.001), LVEF ( OR=0.747, 95% CI 0.656-0.851, P<0.001) and 24-h urine volume (every 100 ml increase, OR=0.842, 95% CI 0.763-0.929, P=0.001) were independently correlated with heart failure. Conclusions:The cut-off value of plasma NT-proBNP for diagnosing or predicting heart failure in peridialysis CKD patients is much higher than that in patients with normal renal function. NT-proBNP, LVEF and 24-h urine volume are independently associated with heart failure in peridialysis CKD patients.

Objective:To study the characteristics of mathematical cognitive function in children with sleep-disordered breathing(SDB) by event-related potential (ERP).Methods:From October 2020 to October 2022, totally 22 cases of SDB children and 22 cases of normal children aged 8-11 were selected.All subjects performed mathematic tasks including calculating and deciding.The EEG changes and behavioral data of children with SDB and normal children were recorded.The latency and amplitude of N1, P2, N2, P3 in leads Fz were measured and compared by Matlab. SPSS 23.0 software was used for statistical analysis, and t test or Mann Whitney U test were used for two independent sample data. Results:(1)Behavior test: the interaction effect between group and type, the group main effect, and the type main effect in accuracy between SDB group and normal group were not significant ( F=0.470, 3.590, 0.003, all P>0.05). The group main effect and interaction effect between group and type in reaction time between SDB group and normal group were not significant ( F=0.465, 1.991, both P>0.05), while the type main effect was significant ( F=18.010, P<0.05). (2)ERP test: the N2, P3 latencies for addition in children with SDB were longer than those in normal group(N2: (371.38±34.23)ms vs (348.12±26.34)ms; P3: (610.72±64.78)ms vs (529.05±30.25)ms)( t=2.526, 5.358, both P<0.05). There was no significant difference between SDB group and normal group in ERP latency and amplitude for subtraction(both P>0.05). The N2, P3 latencies for multiplication in children with SDB were longer than those in normal group(N2: (439.20±24.28)ms vs (351.14±25.26)ms; P3: (531.71±35.42)ms vs (415.23±19.01)ms)( t=11.792, 13.590, both P<0.05). The P3 amplitudes in children with SDB was higher than that in normal group(P3: (3.16±4.78)μV vs (0.38±3.27)μV)( t=2.248, P<0.05). The P3 latency for correct judgment in children with SDB was longer than that in normal group(P3: (420.38±34.79)ms vs (398.54±33.71)ms)( t=2.115, P<0.05). The P3 latency for wrong judgment in children with SDB was longer than that in normal group(P3: (475.25±51.11)ms vs (414.88±27.53)ms)( t=4.878, P<0.05). Conclusion:The latency of N2 and P3 in ERP of SDB children is prolonged, and P3 latency is more sensitive than N2, indicating that SDB children have impairment of mathematical cognitive function.The latency changes of N2 and P3 occurs earlier than the behavioral changes (reaction time and accuracy), which can be used as one of the electrophysiological indicators for early assessment of mathematical cognitive impairment in SDB children.

Objective: Physical literacy is the breakthrough point and fundamental goal to achieve the integration of sports and education, sports and public health and expand the function of physical education. Studying the children and adolescents physical literacy is a common responsibility for children and adolescents health, sports and health education workers. This article was based on the latest research evidence and expert opinions in China, aiming to develop the core items of physical literacy guidelines for Chinese children and adolescents. Methods: This article systematically combed the dimensions and index system of children and adolescents physical literacy through systematic literature review. After five rounds of Delphi methods, the core items were extracted. Results: The core items included four interrelated dimensions of body, emotion, behavior, and cognition, which were specifically composed of four components: physical ability, emotional experience, physical activity related behaviors, and knowledge understanding and application ability. Conclusion Children and adolescents are the key periods, sensitive periods, and window periods to cultivate physical literacy. The core items can provide framework recommendations for further refining guidelines. More empirical studies should be carried out in the future, in order to accumulate enough evidences and further to improve Physical Literacy guidelines, better to guide physical literacy promotion.

OBJECTIVE: To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells. METHODS: Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting. RESULTS: Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 ( CONCLUSIONS Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.
Cell Cycle ; Cell Cycle Checkpoints ; Cellular Senescence ; Epithelial Cells ; Humans ; Piperazines/pharmacology* ; Pyridines/pharmacology* ; Tumor Suppressor Protein p53/genetics*

OBJECTIVE: To investigate the effect of blocking pannexin-1 against acute kidney injury induced by cisplatin. METHODS: Twenty-six male C57BL/6 mice aged 6-8 weeks were randomly divided into control group, cisplatin model (Cis) group and cisplatin + carbenoxolone treatment group (Cis + CBX). In Cis group and Cis + CBX group, the mice were injected intraperitoneally with 20 mg/kg of cisplatin and with CBX (20 mg/kg) at 30 min before and 24 and 48 h after cisplatin inhjection, respectively. All the mice were sacrificed at 72 h after cisplatin injection, and plasma and kidney samples were collected for testing mRNA and protein expression levels of pannexin-1 in the renal tissue using RT-qPCR and Western blotting and for detecting plasma creatinine and BUN levels; the pathological changes in the renal tissues were observed using Periodic Acid-Schiff staining. The expression of kidney injury molecule 1 (KIM-1) was examined using immunohistochemistry and the mRNA expressions of KIM-1 and neutrophil gelatinase- related lipid transport protein (NGAL) were detected by RT-qPCR to evaluate the injuries of the renal tubules. The infiltration of F4/80-positive macrophages and CD4-positive T cells were observed by immunofluorescence. In the experiment, human proximal tubule epithelial cell line HK-2 was stimulated with 50 μmol/L cisplatin to establish a cell model of acute kidney injury, and the mRNA and protein expressions of pannexin-1 were detected by RT-qPCR and Western blotting at 4, 6, 12, 18 and 24 h after the stimulation. RESULTS: Compared with the control mice, the cisplatin-treated mice showed significantly up-regulated protein levels ( < 0.05) and mRNA levels ( < 0.005) of pannexin-1 in the kidney tissue. Cisplatin stimulation also caused significant increases in the protein levels ( < 0.005) and mRNA levels ( < 0.005) of pannexin-1 in cultured HK-2 cells. Compared with cisplatin-treated mice, the mice treated with both cisplatin and the pannexin-1 inhibitor CBX showed obviously lessened kidney pathologies and milder renal tubular injuries with significantly reduced plasma BUN and Scr levels ( < 0.01), expressions of KIM-1 and NGAL in the kidney ( < 0.05), and infiltration of F4/80-positive macrophages ( < 0.01) and CD4- positive T cells ( < 0.05) in the kidney tissues. CONCLUSIONS In cisplatin induced acute kidney injury mice model, Pannexin-1 expression is up-regulated in the kidneys tissue, and blocking pannexin-1 alleviates the acute kidney injury reducing renal inflammatory cell infiltration.
Acute Kidney Injury ; drug therapy ; metabolism ; Animals ; Cisplatin ; pharmacology ; Connexins ; drug effects ; metabolism ; Cross-Linking Reagents ; pharmacology ; Humans ; Kidney ; Kidney Tubules ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; drug effects ; metabolism ; Random Allocation

Objective:To investigate the relationship between serum carcinoembryonic antigen (CEA) and the predictive value of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients, as well as to analyze further EGFR muta-tions and CEA levels affecting patient survival. Methods:From March 2009 to March 2011, a total of 387 cases were treated in the Lung Cancer Department in Tianjin Cancer Hospital. Preoperative CEA tumor marker and postoperative EGFR gene mutation were used for routine detection. The influence of CEA tumor marker on EGFR mutation and its relationship with the prognosis were ana-lyzed further. Results:A total of 168 cases involved EGFR mutations, the incidence of which is more frequent in women, non-smokers, adenocarcinoma patients, and patients below 60 years old (P<0.05). This study also determined that EGFR mutation was related with tu-mor markers and chemosensitivity indicators. Elevated Cyfra21-1, SCC, and ERCC1-positive are more common in wild-type patients (P<0.05). However, abnormal CEA was more common in EGFR mutation patients (P=0.015). The rate of EGFR gene mutations signifi-cantly increased as the serum CEA level increased. Serum CEA levels were divided into three groups (<5, 5-20, and>20). The positive rates of EGFR mutations were 40.1%, 47.5%and 66.6%(P=0.003). Logistic regression analysis determined that CEA levels are inde-pendent factors in predicting EGFR mutations and independent prognostic factors in patients with non-small cell lung cancer. Conclu-sion:Serum CEA levels can independently predict the prognosis of resected non-small cell lung cancer patients, which is has a close re-lationship with EGFR mutations.

Objective To evaluate the effects of KIM-1 on high glucose induced the expression of MCP-1 and FN in rat tubular epithelial cells and to explore the possible mechanisms of KIM-1 involved in renal interstitial fibrosis of DN.Methods The rat renal tubular epithelial cells (NRK52E) were cultured in vitro and divided into five groups:Normal control group (D-glucose 5.6 mmol/L),Hypertonic group (D-glucose 5.6 mmol/L + D-mannitol 24.4 mmol/L),High glucose group (Dglucose 30 rmmol/L),Control siRNA group,KIM-1 siRNA group.ELISA assay was used to assess the levels of MCP-1 and FN in the cells supernatant; Western blotting was used to detect the protein expression of KIM-1; RT-PCR was used to detect mRNA expression of KIM-1,MCP-1 and FN.Results Compared with the control group,the protein and mRNA expression of KIM-1 in the high glucose group were increased at 12 h (P ＜ 0.05),and reached the peak at 48 h (P ＜ 0.05); the protein and mRNA expression of MCP-1 and FN in high glucose group were increased at 24 h significantly (P ＜ 0.05),and peaked at 48 h (P ＜ 0.05).Compared with the high glucose group,the protein and mRNA expressions of MCP-1 and FN in KIM-1 siRNA group were decreased (P＜0.05).Conclusions Down-regulating the expression of KIM-1 can significantly inhibit the expression of MCP-1 and FN,which suggests that KIM-1 may be involved in renal interstitial fibrosis of DN by regulating expression of MCP-1 and FN.

Objective To investigate the effect of valsartan on expression of HIF-1α,TIMP-1,MMP-9 in the process of renal interstitial fibrosis(RIF) in diabetic nephropathy(DN) rats.Methods Fifty-four SD rats were randomly divided to 3 groups:control group (group C),DN group (group D),valsartan treatment group (group T).Rats of group D and T were given streptozocin (STZ) by intraperitoneal injection to establish animal model of diabetes.After diabetic models were successfully made,rats of group T were treated by valsartan (40 mg·kg-1·d-1).Serum glucose,serum creatinine and urinary protein were measured at the 4th,8th and 12th weeks.Masson staining was used to calculate the area of RIF.The methods of immunohistochemistry and real-time PCR were used to detect the expressions of HIF-1α,TIMP-1,MMP-9 in renal interstitium.Results Compared with group C,the areas of RIF were larger,24-hour urinary protein,Scr were higher,the mRNA and protein expression of HIF-1α and TIMP-1 increased,while the mRNA and protein expression of MMP-9 decreased in D and T group (P＜0.05).At the 8th,12th weeks,compared with group D,the areas of RIF were smaller,24-hour urinary protein,Scr were relatively lower expressions of HIF-1α and TIMP-1 decreased,while the eapressions of MMP-9 increased in group T (P＜0.05).Conclusion Valsartan may delay the progress of RIF in DN rats by down-regulating the expressions of HIF-1α,TIMP-1,up-regulating the expression of MMP-9,then improve renal function.