Reciprocal regulation of protein kinase and pyruvate kinase activities of pyruvate kinase M2 by growth signals.

Pyruvate kinase isoform M2 (PKM2) is an enzyme-catalyzing conversion of phosphoenolpyruvate to pyruvate in the glycolysis pathway. It was demonstrated that PKM2 interacts with tyrosine phosphopeptide, and the interaction with the tyrosine phosphopeptide affects the pyruvate kinase activity of PKM2. Our experiments suggest that PKM2 is also an active protein kinase (Gao, X., Wang, H., Yang, J. J., Liu, X., and Liu, Z. R. (2012) Mol. Cell 45, 598-609). We report here that growth signals reciprocally regulate the pyruvate kinase and protein kinase activities of PKM2 by different mechanisms. On the one hand, growth signals induce protein tyrosine phosphorylations. The tyrosine-phosphorylated protein(s) regulates the conversion of pyruvate kinase and protein kinase of PKM2 by directly interacting with PKM2. Binding of the tyrosyl-phosphorylated proteins at the fructose 1,6-bisphosphate-binding site converts the tetrameric PKM2 to a dimer. On the other hand, growth stimulations also lead to PKM2 phosphorylation, which consequently regulates the conversion of protein kinase and pyruvate kinase activities. Growth factor stimulations significantly increase the dimer/tetramer PKM2 ratio in cells and consequently activate the protein kinase activity of PKM2. Our study suggests that the conversion between the pyruvate kinase and protein kinase activities of PKM2 may be an important mechanism mediating the effects of growth signals in promoting cell proliferation.

Structure and antitumor and immunomodulatory activities of a water-soluble polysaccharide from Dimocarpus longan pulp.

A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) analysis. The results indicated that the molecular weight of the sample was 1.1 × 10(5) Da. Monosaccharide composition analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of a backbone of → 4)-α-D-Glcp-(1 → 4)-α-D-GALPA-(1 → 4)-α-D-Glcp-(1 → 4)-ß-D-Glcp-(1 → units with poly saccharide side chains composed of → 2)-ß-D-Fruf-(1 → 2)-L-sorbose-(1 → attached to the O-6 position of the α-D-Glcp residues. In vitro experiments indicated that LP1 had significantly high antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition percentages of 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon-γ (IFN-γ), increased the activity of murine macrophages and enhanced B- and T-lymphocyte proliferation. The results of this study demonstrate that LP1 has potential applications as a natural antitumor agent with immunomodulatory activity.

Hemp seeds attenuate loperamide-induced constipation in mice.

Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve constipation, however the specific mechanism is still unclear. This study investigates that hemp seed (HS) and its water-ethanol extract (HSE) attenuates loperamide-induced constipation in mice. The research results show that: the fecal water content and small intestinal transit rate of mice in the hemp seed group and hemp seed hydroalcoholic extract group were significantly increased compared with MC group, and the first red feces defecation time was significantly shortened; HS and HSE significantly influence serum levels of Gastrin (Gas), motilin (MTL), substance P (SP), and endothelin (ET), potentially mediating their effects on gastrointestinal motility. HS and HSE can improve colon inflammation in constipated mice with H&E staining. Compared with the model of constipation group, the content of short-chain fatty acids in the HS group and HSE group increased significantly. Gut microbiome studies have shown that the structure and abundance of intestinal flora are altered. HS and HSE changed the abundance of Odoribacter, Bacteroide, Lactobacillus and Prevotella. Together, these results suggest that HS have the potential to stimulate the proliferation of beneficial gut microbes and promote intestinal motility, thereby improving gut health and relieving symptoms of constipation.

Peptides derived from growth factors: Exploring their diverse impact from antimicrobial properties to neuroprotection.

Growth factor-derived peptides are bioactive molecules that play a crucial role in various physiological processes within the human body. Over the years, extensive research has revealed their diverse applications, ranging from antimicrobial properties to their potential in neuroprotection and treating various diseases. These peptides exhibit innate immune responses and have been found to possess potent antimicrobial properties against a wide range of pathogens. Growth factor-derived peptides have demonstrated the ability to promote neuronal survival, prevent cell death, and stimulate neural regeneration. As a result, they hold immense promise in the treatment of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, as well as in the management of traumatic brain injuries. Moreover, growth factor-derived peptides have shown potential for supporting tissue repair and wound healing processes. By enhancing cell proliferation and migration, these peptides contribute to the regeneration of damaged tissues and promote a more efficient healing response. The applications of growth factor-derived peptides extend beyond their therapeutic potential in health; they also have a role in various disease conditions. For example, researchers have explored their influence on cancer cells, where some peptides have demonstrated anti-cancer properties, inhibiting tumor growth and promoting apoptosis in cancer cells. Additionally, their immunomodulatory properties have been investigated for potential applications in autoimmune disorders. Despite the immense promise shown by growth factor-derived peptides, some challenges need to be addressed. Nevertheless, ongoing research and advancements in biotechnology offer promising avenues to overcome these obstacles. The review summarizes the foundational biology of growth factors and the intricate signaling pathways in various physiological processes as well as diseases such as cancer, neurodegenerative disorders, cardiovascular ailments, and metabolic syndromes.

Treatment of polycystic liver disease: a hypothesis, patient characteristics, short and long-term results.

BACKGROUND: Non-total liver resecting invasive treatment of polycystic liver disease has different recurrence rates. The aim of this study is to illustrate why the recurrence rates are different. We established a hypothesis that the cyst number is a constant in polycystic liver disease in a patient's lifetime. MATERIAL AND METHODS: We selected 287 patients with polycystic liver, in which 35 patients had the record of liver volume, while other 252 patients had the record of length of right liver. Data were divided into 5 groups in terms of age. The intergroup comparison with different ages and clinical files of patients were analyzed. RESULTS: The mean difference was statistically insignificant when compared amongst groups in the lengths of right liver respectively. Symptom recurrence rates (q) were 19.05 and 17.65% respectively after cyst aspiration-sclerotherapy and non-cyst aspiration-sclerotherapy. CONCLUSION: The cyst number is a constant in patients with non-massive or massive polycystic liver disease in their lifetime.

LncRNA GAS5/miR-137 Is a Hypoxia-Responsive Axis Involved in Cardiac Arrest and Cardiopulmonary Cerebral Resuscitation.

Background: Cardiac arrest/cardiopulmonary resuscitation (CA/CPR) represents one of the devastating medical emergencies and is associated with high mortality and neuro-disability. Post-cardiac arrest syndrome (PCAS) is mechanistically ascribed to acute systemic ischemia/reperfusion(I/R) injury. The lncRNA/microRNA/mRNA networks have been found to play crucial roles in the pathogenesis of the hypoxia-responsive diseases. Nonetheless, the precise molecular mechanisms by which lncRNA/miRNA/mRNA axes are involved in the astrocyte-microglia crosstalk in CA/CPR have not been fully elucidated. Methods: We collected and purified the exosomes from the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. On the basis of microarray analysis, bioinformatic study, and luciferase activity determination, we speculated that lncRNA GAS5/miR-137 is implicated in the astrocyte-microglia crosstalk under the insult of systemic I/R injury. The regulation of lncRNA GAS5/miR-137 on INPP4B was examined by cellular transfection in OGD/R cell culture and by lateral ventricle injection with miR-137 agomir in CA/CPR mice model. Flow cytometry and immunofluorescence staining were performed to detect the microglial apoptosis, M1/M2 phenotype transformation, and neuroinflammation. Neurological scoring and behavior tests were conducted in CA/CPR group, with miR-137 agomir lateral-ventricle infusion and in their controls. Results: In all the micRNAs, miR-137 was among the top 10 micRNAs that experienced greatest changes, in both the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. Bioinformatic analysis revealed that miR-137 was sponged by lncRNA GAS5, targeting INPP4B, and the result was confirmed by Luciferase activity assay. qRT-PCR and Western blotting showed that lncRNA GAS5 and INPP4B were over-expressed whereas miR-137 was downregulated in the blood of CA/CPR patients, OGD/R-stimulated astrocytes, and brain tissue of CA/CPR mice. Silencing lncRNA GAS5 suppressed INPP4B expression, but over-expression of miR-137 negatively modulated its expression. Western blotting exhibited that PI3K and Akt phosphorylation was increased when lncRNA GAS5 was silenced or miR-137 was over-expressed. However, PI3K and Akt phosphorylation was notably suppressed in the absence of miR-137, almost reversing their phosphorylation in the silencing lncRNA GAS5 group. Then we found that GAS5 siRNA or miR-137 mimic significantly increased cell viability and alleviated apoptosis after OGD/R injury. Furthermore, over-expression of miR-137 attenuated microglial apoptosis and neuroinflammation in CA/CPR mice model, exhibiting significantly better behavioral tests after CA/CPR. Conclusion: LncRNA GAS5/miR-137 may be involved in the astrocyte-microglia communication that inhibits PI3K/Akt signaling activation via regulation of INPP4B during CA/CPR.

Detection of meat from horse, donkey and their hybrids (mule/hinny) by duplex real-time fluorescent PCR.

Meat adulteration is currently a common practice worldwide. In China, adulteration of donkey meat products with the similar species (horse and mule/hinny) meat and mislabeling are becoming widespread concerns. In this study, a sensitive and species-specific duplex real-time PCR assay based on the simultaneous amplification of fragments of the creatine kinase muscle gene family, was developed and optimized for the identification of horse, donkey and mule /hinny species in raw and heat-processed meat products. Duplex real-time PCR results showed different fluorescence amplification curves for horse and donkey. Both kinds of fluorescence amplification curves appeared simultaneously for mule/hinny. The limit of detection (LOD) of the method was up to 0.01 ng /µL. The method and strategy developed in this study could be applied to detect the presence of adulterants from horse and mule /hinny meat in raw donkey meat and meat products.

An 8­gene signature predicts the prognosis of cervical cancer following radiotherapy.

Gene expression and DNA methylation levels affect the outcomes of patients with cancer. The present study aimed to establish a multigene risk model for predicting the outcomes of patients with cervical cancer (CerC) treated with or without radiotherapy. RNA sequencing training data with matched DNA methylation profiles were downloaded from The Cancer Genome Atlas database. Patients were divided into radiotherapy and non­radiotherapy groups according to the treatment strategy. Differently expressed and methylated genes between the two groups were identified, and 8 prognostic genes were identified using Cox regression analysis. The optimized risk model based on the 8­gene signature was defined using the Cox's proportional hazards model. Kaplan­Meier survival analysis indicated that patients with higher risk scores exhibited poorer survival compared with patients with lower risk scores (log­rank test, P=3.22x10­7). Validation using the GSE44001 gene set demonstrated that patients in the high­risk group exhibited a shorter survival time comprared with the low­risk group (log­rank test, P=3.01x10­3). The area under the receiver operating characteristic curve values for the training and validation sets were 0.951 and 0.929, respectively. Cox regression analyses indicated that recurrence and risk status were risk factors for poor outcomes in patients with CerC treated with or without radiotherapy. The present study defined that the 8­gene signature was an independent risk factor for the prognosis of patients with CerC. The 8­gene prognostic model had predictive power for CerC prognosis.

[Relationship between natural extinction of Oncomelania hupensis snails and water chemical properties in Eastern Dongting Lake areas].

OBJECTIVE: To investigate the reasons of natural extinction of Oncomelania hupensis snails by comparing the difference of the water chemical properties between the snail-breeding marshland and non-snail marshland in Eastern Dongting Lake areas. METHODS: Three adjoining marshlands in Eastern Dongting Lake areas were selected, one was a snail-breeding marshland, the second was a non-snail marshland, and the third was a boundary zone between them. During the periods of water-rising season, wet season and water-falling season, the water samples from the bottom of 0.5 m were collected by the systematic random sampling method (200 m × 200 m grid method). In addition, the water samples below the surface of 0.5 m were also collected in the wet season. The physicochemical indexes of the sampling water were detected. RESULTS: According to the Surface Water Environmental Quality Standard (GB 3838-2002), the water quality indicators which were less than the detection limit were Cr, Cd, Zn, Hg, Cu, S－ and CN－ during the three sampling seasons. The pollutants which were slightly higher than Grade III but lower than Grade IV (Hg ≤ 1 µg/L, TP ≤ 0.1 mg/L) were Hg and TP. The pollutants below the Grade III included As and F－. The temperature and pH values were within the Grade III. The oxygen consumption indicators covering DO, COD and BOD in the water-rising season and wet season were within the Grade III, while the value of BOD was beyond the scope of Grade III but was between Grade Ⅳ (≤ 6 mg/L) and Grade V (≤ 10 mg/L) in the water-falling season. The differences of the water pollution indexes between the snail-breeding marshland and non-snail marshland were statistically significant, and these indexes included F－, As and pH in the water-rising season (P < 0.05); pH, BOD and Fat the surface layer in the wet season (P < 0.05); F－ at the bottom in the wet season (P < 0.05); TP and F－ in the water-falling season. Moreover, the above-mentioned indexes in the non-snail marshland of Qianliang Lake were higher than those in the snail-breeding marshland of Junshan Park. Thus, F－ was the only index which had statistical differences in every sampling season, and the concentration of F－ at the non-snail marshland was also higher than that at the snail-breeding marshland. In the water-rising season, the pH value at the non-snail marshland exceeded the suitable range for the growth of snails (6.8 to 7.8). CONCLUSIONS: In the Eastern Dongting Lake area, the high concentration of F－ and pH of water may be responsible for the natural extinction of O. hupensis snails.

The vertical distributions of VOCs in the atmosphere of Beijing in autumn.

Volatile organic compounds (VOCs) in the air of Beijing City were measured at the heights of 8, 32, 140 and 280 m on the Beijing 325 m meteorological tower in autumn 2005. Concentrations of fifty-five compounds were determined by quantitative analytical methods. Our study utilized GC/MS analysis of 0.5 l air sample that were cryo-concentrated prior to analysis. The vertical distributions of VOCs were also investigated using 1-butene, isopentane, dichloromethane and toluene as representative compounds of several different categories. It is shown that 1-butene followed by 2-butene, isopentane followed by n-pentane, dichloromethane followed by chloroform and toluene followed by benzene are the most abundant compounds in the categories of alkene, alkane, halocarbon and aromatic hydrocarbon, respectively. The concentrations of TVOCs range from 51.2+/-39.7 ppb to 83.6+/-44.4 ppb on clear days, but from 62.9+/-19.0 ppb to 105.0+/-59.2 ppb on haze days. While alkenes and halocarbons contribute little to TVOCs, alkanes provide the largest percentage, ranging from about 46% to 63% at four different heights, which are followed by aromatic hydrocarbons ranging from about 15% to 27%. The vertical distributions of VOCs are complex. On clear days most distribution profiles show a decreasing trend with increasing height. On haze days, however, they exhibit first a decrease with increasing altitude from 8 m to 140 m and then a significant increase at 280 m. These results are understood by analyzing how the vertical distributions of VOCs are affected jointly by several factors such as meteorological parameters and transport property. In addition, principal components analysis (PCA) and cluster analysis show that VOCs have different origins at different heights.

Effect of Mini-Trampoline Physical Activity on Executive Functions in Preschool Children.

The study investigated the effect of mini-trampoline physical activity on the development of executive functions (EF) in Chinese preschool children. Fifty-seven children aged 3-5 were randomly assigned to an intervention group (n = 29) and a control group (n = 28). The children in the intervention and control group had the same classes and care service in the preschool, but children in the intervention group had an extra 20 min of trampoline training after school for 5 school days per week in the 10-week intervention. Spatial conflict arrow (SCA), animal Go/NoGo (GNG), working memory span (WMS), and flexible item selection (FIS) were used to assess children's EF before and after the intervention. Results revealed that no significant differences emerged in the SCA, GNG, WMS, and FIS tests between two groups postintervention. Findings indicated that a 10-week trampoline PA training may not be sufficient to trigger the improvement of preschool children's EF. Future research with larger representative samples is warranted to discern the dose-response evidence in enhancing young children's EF through physical activity.

[Research on living status of Oncomelania hupensis in autumn and winter and its correlates in Eastern Dongting Lake area].

OBJECTIVE: To explore the dynamic changes of Oncomelania hupensis snail densities in autumn and winter and the relationship between hydrological and meteorological factors and snail growth and decline. METHODS: From Octobers to Decembers of 2007 to 2014, a bottomland close to eastern Dongting Lake was selected as the study field. The snails and elevation of the points were surveyed, and the hydrological and meteorological data were collected. The snail densities and death rates of every month were calculated. The meteorological and hydrological data were described, and the relationship between the snail densities and associated factors were fitted by the multiple regression model. RESULTS: The snail density was highest in October 2012 (41.88 per 0.1 m2) and lowest in November 2008 (1.23 per 0.1 m2). The snail mortality was highest in November 2008 (73.72%) and lowest in October 2012 (1.09%). The multiple regression model found a linear relationship between hydrological and meteorological factors and snail densities. The correlation coefficient between the prediction of ln (snail density) and its measurements by using this model was 0.927 (P = 0.001). CONCLUSIONS: The average minimum temperature in January and time of starting flood have an obvious influence on the snail densities in autumn and winter.

Investigation on Fe, Mn, Zn, Cu, Pb and Cd fractions in the natural surface coating samples and surficial sediments in the Songhua River, China.

Natural surface coating samples (NSCSs) from the surface of shingles and surficial sediments (SSs) in the Songhua River, China were employed to investigate the relationship between NSCSs and SSs in fractions of heavy metals (Fe, Mn, Zn, Cu, Pb, and Cd) using the modified sequential extraction procedure (MSEP). The results show that the differences between NSCSs and SSs in Fe fractions were insignificant and Fe was dominantly present as residual phase (76.22% for NSCSs and 80.88% for SSs) and Fe-oxides phase (20.33% for NSCSs and 16.15% for SSs). Significant variation of Mn distribution patterns between NSCSs and SSs was observed with Mn in NSCSs mainly present in Mn-oxides phase (48.27%) and that in SSs present as residual phase (45.44%). Zn, Cu, Pb and Cd were found dominantly in residual fractions (>48%), and next in solid oxides/hydroxides for Zn, Pb and Cd and in easily oxidizable solids/compounds form for Cu, respectively. The heavy metal distribution patterns implied that Fe/Mn oxides both in NSCSs and SSs were more important sinks for binding and adsorption of Zn, Pb and Cd than organic matter (OM), and inversely, higher affinity of Cu to OM than Fe/Mn oxides in NSCSs and SSs was obtained. Meanwhile, it was found that the distributions of heavy metals in NSCSs and SSs were similar to each other and the pseudo-total concentrations of Zn, Cu, Pb and Cd in NSCSs were greater than those in SSs, highlighting the more importance for NSCSs than SSs in controlling behaviours of heavy metals in aquatic environments.

Antimicrobial resistance surveillance of Salmonella isolates from the First People's Hospital of Yunnan Province, China.

INTRODUCTION: Typhoid fever is a common disease in Yunnan province; however, the resistant phenotype and epidemic characteristics of Salmonella in this area are still unclear. In this study, a 15-year surveillance of antimicrobial susceptibility of Salmonella is reported. METHODOLOGY: From January 1999 to December 2013, Salmonella isolates were recovered from patients in the First People's Hospital of Yunnan Province. Antimicrobial susceptibility was detected and data were analyzed using WHONET5.6. RESULTS: A total of 845 Salmonella isolates were recovered between 1999 and 2013. The most frequently isolated Salmonella serovar was S. Paratyphi A (93%), and 75.1% (635/845) of the isolates were from the young and middle-aged population. The resistance rates of Salmonella spp. to ciprofloxacin, ampicillin, and ceftriaxone increased dramatically during the 15 years. Carbapenems retained the highest and most stable activity against isolates. The resistance rates of all Salmonella isolates to chloramphenicol and sulfamethoxazole were 0.4% (3/845) and 1.8% (15/845), respectively. CONCLUSIONS: As Salmonella isolates have been observed to be resistant to first-line antibiotics, antimicrobial agents should be used rationally and prescriptions should be based on case-by-case susceptibility testing.

Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women.

Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P(meta) = 1.88 × 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, P(meta) = 2.62 × 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 × 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, P(meta) = 8.57 × 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.

Development of an ion mobility spectrometer with a paper spray ionization source.

Paper spray (PS) ionization is a recently developed ion source that has been used to analyze samples in their native environments at ambient pressure without requiring sample preparation or pre-separation. The design of an ion mobility spectrometer (IMS) coupled with PS ionization can help expand IMS applications to on-site detection of complex liquid samples. We report a paper spray ionization ion mobility spectrometer prototype that consists of a PS source and an ion mobility spectrometer optimized using a numerical simulation. The performance of the design was evaluated by measuring 2, 6-di-tert-butylpyridine (2, 6-DtBP). The mobility spectra of the 2, 6-DtBP exhibited a single-product ion peak with reduced mobility calculated at 1.42 cm(2)∕(V s) and a linear response of 0.1-10 µg∕ml, with an estimated detection limit of 0.05 µg∕ml. The Relative Standard Deviation for 1 µg∕ml was 5.7% over 11 measurements. The highest resolving power (47) was measured for 2, 6-DtBP. Based on these preliminary results, the present PSIMS design is expected to become a tool of choice for the rapid analysis of complex liquid samples.