[Synchronization isolation method for multiple types of cells from mouse liver].

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.

[Effect of dyslipidemia on clinical outcome of infertility patients receiving donor eggs].

Objective: To explore the effect of dyslipidemia on the clinical outcome of intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in infertility patients receiving donor eggs. Methods: A total of 118 patients were selected to receive egg donors and ICSI-ET at the First Affiliated Hospital of Nanjing Medical University between April 2007 and December 2020. According to the levels of triacylglycerol, serum cholesterol, high density lipoprotein (HDL), and low density lipoprotein, they were divided into dyslipidemia group (35 cases) and normal blood lipids group (83 cases). The influence of body mass index (BMI) and age was adjusted by 1∶1 propensity score matching, and the general condition and clinical outcome of the two groups were analyzed retrospectively. Finally, the relationship between lipid composition and clinical outcome was analyzed according to patients' age and BMI. Results: (1) Comparing the pre-matching dyslipidemia group with the normal blood lipids group, the BMI of the dyslipidemia group was significantly higher than that of the normal blood lipids group [(23.5±2.4) vs (22.4±2.7) kg/m2], and the embryo implantation rate was significantly lower than that of the normal blood lipids group [13.6% (8/59) vs 27.3% (36/132)], the differences were statistically significant (both P<0.05). (2) There were no significant differences in years of infertility, number of pregnancies, number of abortions, number of transplanted embryos, protocol of endometrial preparation, endometrial thickness on transplantation day and high quality embryo rate between the two groups, through propensity score matching (all P>0.05). The biochemical pregnancy rate [28.6% (10/35)], embryo implantation rate [13.6% (8/59)] and live birth rate [20.0% (7/35)] in dyslipidemia group were significantly lower than those in the normal blood lipids group (P<0.05). The clinical pregnancy rate was lower than that of the normal blood lipids group (P>0.05). (3) The results of stratified analysis showed that the level of HDL in the clinically non-pregnant group was significantly lower than that in the pregnant group in patients ≤ 35 years old [(1.5±0.3) vs (1.8±0.5) mmol/L; P<0.05]. In the overweight recipient patients, the level of HDL of the clinically non-pregnant group was lower than that of the pregnant group (P>0.05). Conclusions: Dyslipidemia significantly reduces the biochemical pregnancy rate, embryo implantation rate and live birth rate in patients with receiving donor eggs. Especially in patients aged ≤35 years old, the reduction of HDL is closely related to adverse pregnancy outcomes.

The association between overweight/obesity and vertebral fractures in older adults: a meta-analysis of observational studies.

A meta-analysis of observational studies was conducted to assess the relationship between overweight/obesity and vertebral fractures in older adults. We found that overweight was related to a decreased risk of vertebral fractures in female and non-Asian populations, while obesity failed to be associated with vertebral fracture risks based on the present data. INTRODUCTION: Recent investigations suggest that the influence of overweight/obesity on fracture risks is site-specific, while conflicting data were reported related to vertebral fracture. This meta-analysis was performed to qualitatively assess the relationship between overweight/obesity and the risk of vertebral fracture. METHODS: MEDLINE, Web of Science, Embase, and Cochrane were searched for relevant observational articles assessing the vertebral fracture risk of the overweight or obese population compared to normal population. Two independent reviewers conducted data extraction and quality assessment. Relative risks (RR) and 95% confidence intervals (CI) were pooled using a random effect model. RESULTS: Eleven studies including 1,078,094 participants were extracted from 1645 records. Pooled RR showed that decreased risk of vertebral fractures was observed in the overweight older adults (RR: 1.16; 95% CI: 1.07-1.26; I2: 51.8%), but not in the obese populations (RR: 0.98; 95% CI: 0.82-1.17; I2: 92.1%). In the subgroup analysis, we found a significant inverse association between overweight and risk of vertebral fracture in women (RR: 0.92; 95% CI: 0.85-1.00; I2: 0.0%), non-Asian areas (RR: 0.89; 95% CI: 0.80-0.99; I2: 40.7%), sample size > 2000 (RR: 0.87; 95% CI: 0.80-0.94; I2: 4.9%), and quality score > 7 (RR: 0.87; 95% CI: 0.79-0.95; I2: 21.9%). Furthermore, pooled studies of sample size > 2000 (RR: 0.66; 95% CI: 0.76, 0.89; I2: 52.1%) and quality score > 7 (RR: 0.75; 95% CI: 0.62, 0.91; I2: 68.1%) showed that the people with obesity had a significantly lower prevalence of vertebral fracture. CONCLUSIONS: Overweight aged adults tend to have a lower vertebral fracture risk. When gender and ethnicity were taken into consideration, the inverse relationship between overweight and vertebral fracture risk were only observed in female and non-Asian populations. Besides, there is insufficient data to conclude the relationship between obesity and the risk of vertebral fractures, and thus, further studies are needed.

Distinct Kondo Screening Behaviors in Heavy Fermion Filled Skutterudites with 4f

CeOs_{4}Sb_{12} (COS) and PrOs_{4}Sb_{12} (POS) are two representative compounds that provide the ideal vantage point to systematically study the physics of multi-f-electron systems. COS with Ce 4f^{1}, and POS with Pr 4f^{2} configurations show distinct properties of Kondo insulating and heavy fermion superconductivity, respectively. We unveiled the underlying microscopic origin by angle-resolved photoemission spectroscopy studies. Their eV-scale band structure matches well, representing the common characters of conduction electrons in ROs_{4}Sb_{12} systems (R=rare earth). However, f electrons interact differently with conduction electrons in COS and POS. Strong hybridization between conduction electrons and f electrons is observed in COS with band dependent hybridization gaps, and the development of a Kondo insulating state is directly revealed. Although the ground state of POS is a singlet, finite but incoherent hybridization exists, which can be explained by the Kondo scattering with the thermally excited triplet crystalline electric field state. Our results help us to understand the intriguing properties in COS and POS, and provide a clean demonstration of the microscopic differences in heavy fermion systems with 4f^{1} and 4f^{2} configurations.

Association of FLAIR vascular hyperintensity and acute MCA stroke outcome changes with the severity of leukoaraiosis.

PURPOSE: The clinical significance of FLAIR vascular hyperintensity (FVH), a marker of collateral circulation in ischaemic stroke, remains controversial. We hypothesised that the association between FVH and outcomes varies with the severity of leukoaraiosis (LA), another marker of collaterals, and that their combined significance may vary with time. METHODS: We included 459 consecutive patients with middle cerebral artery (MCA) stroke. Proximal and distal FVHs were distinguished based on location. LA was divided into two grades, according to Fazekas scores of 0-2 and 3-6. Symptom-to-MRI time was divided into two categories: ≤ 14 days and ≥ 15 days. RESULTS: We found no difference in FVH proportion according to LA grade. Multivariate analysis revealed that LA and FVH status were independently associated with unfavourable outcomes (modified Rankin scale ≥ 2) in patients with symptom-to-MRI times ≤ 14 days (P = 0.008), but not in those with symptom-to-MRI times ≥15 days (P = 0.61). In the group with symptom-to-MRI times ≤14 days, patients with LA 3-6 and FVH(+) (OR, 3.044; 95% CI, 1.116-8.305) were more likely to have unfavourable clinical outcomes compared with patients with LA 0-2 and FVH(+) but not compared with those with LA 0-2 and FVH(-) or LA 3-6 and FVH(-). In addition, FVH location did not influence the relationship between FVH and outcomes. CONCLUSIONS: The association between FVH and outcomes was influenced by the degree of LA in the acute but not in the subacute and chronic stages of MCA infarction. FVH predicts clinical outcomes independently only in those with more extensive LA.

Correction to: Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets.

As part of an institutional investigation by University of Bremen, the work carried out by Kathrin Maedler's laboratory has been reviewed.

Quantum Criticality of the Ising-like Screw Chain Antiferromagnet SrCo_{2}V_{2}O_{8} in a Transverse Magnetic Field.

The quantum criticality of an Ising-like screw chain antiferromagnet SrCo_{2}V_{2}O_{8}, with a transverse magnetic field applied along the crystalline a axis, is investigated by ultralow temperature NMR measurements. The Néel temperature is rapidly and continuously suppressed by the field, giving rise to a quantum critical point (QCP) at H_{C_{1}}≈7.03 T. Surprisingly, a second QCP at H_{C_{2}}≈7.7 T featured with gapless excitations is resolved from both the double-peak structure of the field-dependent spin-lattice relaxation rate 1/^{51}T_{1} at low temperatures and the weakly temperature-dependent 1/^{51}T_{1} at this field. Our data, combined with numerical calculations, suggest that the induced effective staggered transverse field significantly lowers the critical fields, and leads to an exposed QCP at H_{C_{2}}, which belongs to the one-dimensional transverse-field Ising universality.

Non-invasive genetic sexing technique for analysis of short-beaked echidna (Tachyglossus aculeatus) populations.

Identifying male and female echidnas is challenging due to the lack of external genitalia or any other differing morphological features. This limits studies of wild populations and is a major problem for echidna captive management and breeding. Non-invasive genetic approaches to determine sex minimise the need for handling animals and are used extensively in other mammals. However, currently available approaches cannot be applied to monotremes because their sex chromosomes share no homology with sex chromosomes in other mammals. In this study we used recently identified X and Y chromosome-specific sequences to establish a non-invasive polymerase chain reaction-based technique to determine the sex of echidnas. Genomic DNA was extracted from echidna hair follicles followed by amplification of two Y chromosome (male-specific) genes (mediator complex subunit 26 Y-gametolog (CRSPY) and anti-Müllerian hormone Y-gametolog (AMHY)) and the X chromosome gene (anti-Müllerian hormone X-gametolog (AMHX)). Using this technique, we identified the sex of 10 juvenile echidnas born at Perth Zoo, revealing that eight of the 10 echidnas were female. Future use of the genetic sexing technique in echidnas will inform captive management, continue breeding success and can be used to investigate sex ratios and population dynamics in wild populations.

[Risk factors associated with systemic inflammatory response syndrome after flexible ueteroscopic lithotripsy based on enhanced recovery after surgery].

Objective: To investigate the risk factors of systemic inflammatory response syndrome (SIRS) in patients undergoing flexible ureteroscopic lithotripsy based on enhanced recovery after surgery (ERAS). Methods: The clinical data of 243 kidney stone cases who underwent flexible ureteroscopic lithotripsy based on ERAS in the First Affiliated Hospital of Wannan Medical College from January 2016 to December 2017 were analyzed retrospectively. The cases were divided into two groups according to whether they had SIRS after surgery: SIRS group (26 cases) and non-SIRS group (217 cases). The age, gender, laterality of kidney stone, history of previous kidney stone surgery, degree of hydronephrosis, multiple kidney stones, length of operation time, white blood cell count of preoperative urine routine, result of preoperative urine culture, use of preoperative antibiotics, diabetes and other chronic diseases in the groups were collected and analyzed. Results: SIRS occurred in 26 cases in this study, which accounted for 10.7% (26/243). Multivariate analysis found that, moderate and severe hydronephrosis (OR=6.711, P=0.008), stone burden ≥2 cm (OR=10.353, P<0.001), length of operation time ≥ 60 min (OR=5.583, P=0.011), white blood cell count of preoperative urine routine ≥25×10(6)/L (OR=6.195, P=0.005), positive preoperative urine culture (OR=4.216, P=0.011), diabetes and other chronic diseases (OR=4.532, P=0.006) were the independent risk factors for postoperative SIRS (P<0.05). Conclusions: The occurrence of SIRS after flexible ureteroscopic lithotripsy based on ERAS is closely correlated with hydronephrosis, stone burden, length of operation time, white blood cell count of preoperative urine routine, positive preoperative urine culture, diabetes and other chronic diseases.

Band Dependent Interlayer f-Electron Hybridization in CeRhIn_{5}.

A key issue in heavy fermion research is how subtle changes in the hybridization between the 4f (5f) and conduction electrons can result in fundamentally different ground states. CeRhIn_{5} stands out as a particularly notable example: when replacing Rh with either Co or Ir, antiferromagnetism gives way to superconductivity. In this photoemission study of CeRhIn_{5}, we demonstrate that the use of resonant angle-resolved photoemission spectroscopy with polarized light allows us to extract detailed information on the 4f crystal field states and details on the 4f and conduction electron hybridization, which together determine the ground state. We directly observe weakly dispersive Kondo resonances of f electrons and identify two of the three Ce 4f_{5/2}^{1} crystal-electric-field levels and band-dependent hybridization, which signals that the hybridization occurs primarily between the Ce 4f states in the CeIn_{3} layer and two more three-dimensional bands composed of the Rh 4d and In 5p orbitals in the RhIn_{2} layer. Our results allow us to connect the properties observed at elevated temperatures with the unusual low-temperature properties of this enigmatic heavy fermion compound.

[Cumulative live birth rates per oocytes retrieved cycle: evaluation of clinical outcomes of IVF/ICSI].

Objective: Using of cumulative live birth rate (CLBR) per oocytes retrieved cycle, to assess the clinical outcomes of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) , and to explore impact factors on CLBR following utilization of all fresh and frozen embryos in one complete IVF/ICSI cycle using gonadotropin-releasing hormone (GnRH) agonist, GnRH-antagonist and clomiphene mild stimulation protocols. Methods: Of the patients who underwent IVF/ICSI from January 1st, 2014 to December 31st, 2015 in the First Affiliated Hospital, Nanjing Medical University, a total of 6 142 oocytes retrieved cycles were included. The clinical and laboratory parameters of different ovarian stimulation protocols, and the effects of the age, number of oocytes retrieved and number of embryos available on the CLBR of each oocytes retrieved cycle were analyzed. Results: The CLBR was 69.0% (2 004/2 906) in the GnRH-agonist protocol versus 67.4% (644/955) in the GnRH-antagonist protocol (P>0.05); the CLBR of clomiphene mild stimulation protocol was 53.2% (1 215/2 281) , significantly lower than those of the other two protocols (all P<0.05). The CLBR significantly decreased with age increased. When divided into four groups according to the patients' age, we found that CLBR were not statistically significant using three different protocols in the 20-25 years old group (all P>0.05). There was a strong association between the number of oocytes retrieved and embryos available on CLBR. CLBR rose significantly with an increasing number of oocytes up to 6, then the rising trend slowed down. Patients were categorized into four groups according to the number of oocytes retrieved, CLBR was significantly higher using GnRH-antagonist protocol (50.0%) than mild stimulation protocol (37.0%) in low ovarian responder (0-4 oocytes) group (P<0.05) . The CLBR were no significant difference among three protocols in normal (10-15 oocytes) and high responders (≥15 oocytes) group (all P>0.05) . The incidence rate of ovarian hyperstimulation syndrome in GnRH-agonist protocols (5.2%, 152/2 906) were significantly higher than those of GnRH-antagonist (4.4%, 42/955) and clomiphene mild stimulation protocols (1.5%, 34/2 281; all P<0.05) . Conclusions: CLBR is an important index to assess the clinical outcomes of IVF/ICSI. Age, number of oocytes retrieved and embryos available could affect CLBR obviously. According to the different age and ovarian response of patients, we should design ovarian stimulation protocols based on target oocytes number in order to get higher CLBR and reduce complications.

[Efficacy of patient-controlled intravenous analgesia with hydromorphone hydrochloride plus flurbiprofen axetil after endoscopic sinus surgery].

Objective: To evaluate the efficacy of patient-controlled intravenous analgesia (PCIA)with hydromorphone hydrochloride plusflurbiprofen axetil after endoscopic sinus surgery(ESS). Methods: One hundred patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for ESS under total intraveous anesthesia with postoperative PCIA in Beijing Tongren Hospital from October 2015 to April 2016 were randomly divided into 3 groups according to the different formula of PCIA pumpin each group: Group A (hydromorphone hydrochloride 1 µg·kg(-1)·h(-1)+ flurbiprofen axetil 200 mg), Group B(hydromorphone hydrochloride 2 µg·kg(-1)·h(-1)), Group C( hydromorphone hydrochloride 1 µg·kg(-1)·h(-1)). The dosage of PCIA in each group was calculated for 50 h, and was diluted in 100 ml normal saline. All the pump was set up background infusion at a rate of 2 ml/h with a 2 ml bolus dose and a 15 min lock-time.Visual analogue scale (VAS) and Ramsay sedation scores at time points of postoperative 1, 4, 8, 12, 24, 48 h, the number of attempts to press bolus and rate of adverse effects within 48 h were recorded. The differences were compared among the groups. Results: VAS at postoperative 1, 4, 8, 12 h in Group A was (1.9±0.6), (1.8±0.6), (1.6±0.6), and (1.2±0.4) respectively, in Group B was (1.8±0.4), (1.7±0.7), (1.6±0.6), and (1.3±0.5) respectively, in Group C was (2.5±0.9), (1.7±0.7), (1.6±0.6), and (1.3±0.5) respectively. The difference among each group were statistically significant (F=8.661, 3.105, 4.903, 13.846, P<0.05). VAS in Group A was similar to that in Group B(P>0.05), but was lower than that in Group C(P<0.05). The number of attempts to press bolus within 48 h in group A was 1.4±1.0, which was less than in Group C(2.2±1.8 , P<0.05). Ramsay sedation score at postoperative 1, 4, 8 h in Group A was (2.4±0.6), (2.2±0.6), and (2.2±0.4) respectively, in Group B was (2.8±0.7), (2.6±0.7), and (2.4±0.6) respectively, in Group C was (2.3±0.6), (2.1±0.4), and (2.1±0.2) respectively. The difference among each group were statistically significant (F=5.660, 6.782, 7.141, P<0.05). Ramsay sedation score in group A was similar to that in Group C(P>0.05), but was lower than that in Group B(P<0.05). The total rate of adverse effects in Group A was 8.8%, which was similar to that in Group C (9.1%, χ(2)=0.001, P>0.05), but was significantly lower than that in Group B (42.5%, χ(2)=9.99, P<0.05). Conclusion: 1 µg·kg(-1)·h(-1) hydromorphone hydrochloride plus 200 mg flurbiprofen axetil is effective on PCIA for patients after ESS and can reduce the dosage of hydromorphone hydrochloride and the rate of adverse effects as well.

[Analysis of clinical outcomes of different embryo stage biopsy in array comparative genomic hybridization based preimplantation genetic diagnosis and screening].

Objective: To evaluate the efficiency of the application of array comparative genomic hybridization (array-CGH) in preimplantation genetic diagnosis or screening (PGD/PGS), and compare the clinical outcomes of different stage embryo biopsy. Methods: The outcomes of 381 PGD/PGS cycles referred in the First Affiliated Hospital of Nanjing Medical University from July 2011 to August 2015 were retrospectively analyzed. There were 320 PGD cycles with 156 cleavage-stage-biopsy cycles and 164 trophectoderm-biopsy cycles, 61 PGS cycles with 23 cleavage-stage-biopsy cycles and 38 trophectoderm-biopsy cycles. Chromosomal analysis was performed by array-CGH technology combined with whole genome amplification. Single embryo transfer was performed in all transfer cycles. Live birth rate was calculated as the main clinical outcomes. Results: The embryo diagnosis rate of PGD/PGS by array-CGH were 96.9%-99.1%. In PGD biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were 50.0%(58/116) and 37.2%(58/156) in cleavage-stage-biopsy group, 67.5%(85/126) and 51.8%(85/164) in trophectoderm-biopsy group (both P<0.01). In PGS biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were the same as 34.8%(8/23) in cleavage-stage-biopsy group, the same as 42.1%(16/38) in trophectoderm-biopsy group (both P>0.05). Conclusions: High diagnosis rate and idea live birth rate are achieved in PGD/PGS cycles based on array-CGH technology. The live birth rate of trophectoderm-biopsy group is significantly higher than that of cleavage-stage-biopsy group in PGD cycles; the efficiency of trophectoderm-biopsy is better.

Low-temperature behaviors of the dipolar magnet Dy3Sb3Zn2O14with a strongly site-mixing disordered kagome lattice.

Interesting behaviors may emerge in the magnetic frustrated materials with significant site-mixing disorder. We present the results of the structural, magnetic susceptibility, and specific heat measurements of Dy3Sb3Zn2O14with ∼20%Dy/Zn site-mixing disorder, which results in either a diluted 2D triangular lattice, or an intermediate structure between the kagome and pyrochlore lattice. In addition to the sharp anomaly of the temperature dependence of specific heat atT∼0.35 K, which was attributed to the emergent charge order state for the sample with less disorder, a broad peak atT∼1.5 K, and a small hump belowT∼0.1 K are observed. The measured temperature dependence of specific heat and the Monte Carlo simulation suggest that the magnetic frustration persists despite of a strong site-mixing disorder.

Clinical features, STAT3 gene mutations and Th17 cell analysis in nine children with hyper-IgE syndrome in mainland China.

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency disease characterized by eczema, recurrent staphylococcal aureus skin abscesses, pneumonia with pneumatocele formation, remarkably high serum IgE levels, eosinophilia and involvement of skeleton and connective tissues. Heterozygous signal transducer and activator of transcription 3 (STAT3) mutations were shown to be the cause of autosomal dominant HIES (AD-HIES). In this study, we diagnosed nine patients with HIES from 9 unrelated families on the basis of a National Institutes of Health (NIH) score of ≥40 points, sequenced the STAT3 gene of all nine patients, and quantified Th17 cells in peripheral blood of seven patients by flow cytometry in mainland China. All nine patients had characteristic manifestation of HIES with the range of NIH scores 45-77 points. STAT3 hot mutations V637M or R382W/Q were identified in five patients. We identified two novel heterozygous missense mutations (T620S and R609G) located in Src homology 2 (SH2) domain in two patients, respectively. In two other patients, no STAT3 mutations were found. Quantified Th17 cell numbers were markedly decreased or absent (0-0.28% of CD4(+) T cells) in six patients with STAT3 mutations and almost normal (0.53% of CD4(+) T cells) in one wild-type STAT3 patient compared with healthy controls (0.40-2.25% of CD4(+) T cells). These results suggest that not all patients with HIES who had NIH scores over 40 points carry STAT3 mutations, those whose Th17 cell numbers strikingly decreased probably had AD-HIES with STAT3 mutations.

TCF7L2 promotes beta cell regeneration in human and mouse pancreas.

AIMS/HYPOTHESIS: Diabetes is characterised by loss and dysfunction of the beta cell. A major goal of diabetes therapy is to promote the formation of new beta cells. Polymorphisms of T cell factor 7-like 2 (TCF7L2) are associated with type 2 diabetes, negatively regulating beta cell survival and function. Here, we provide evidence for a role of TCF7L2 in beta cell proliferation and regeneration. METHODS: Pancreatic sections from three mouse models (high-fat diet, exendin-4 and streptozotocin-treated mice) and from healthy individuals and patients with type 2 diabetes were used to investigate the association of beta cell regeneration and TCF7L2 levels. To analyse a direct effect of TCF7L2 on duct cell to beta cell conversion, TCF7L2 was overexpressed in isolated exocrine cells. RESULTS: TCF7L2 levels correlated with beta cell compensation during high-fat diet feeding. TCF7L2 was increased together with pancreatic duct cell proliferation and differentiation. Small islet-like cell clusters (ICCs) that contained TCF7L2 originated in the vicinity of the ductal epithelium. In human isolated exocrine tissue, TCF7L2 overexpression induced proliferation of pancreatic duct cells and ICC formation next to duct cells, an effect dependent on the JAK2/STAT3 pathway. CONCLUSIONS/INTERPRETATION: The present study demonstrates that TCF7L2 overexpression fosters beta cell regeneration. Our findings imply correlation of TCF7L2 levels and new beta cell formation.

Treatment of ametryn in wastewater by a hybrid MBR system: a lab-scale study.

Agricultural discharge of herbicides to the Great Barrier Reef (GBR) poses significant threat to the marine ecosystem. This study evaluates the performance of a hybrid treatment system consists of a membrane bioreactor (MBR), UV disinfection unit and a granular activated carbon (GAC) column in treating ametryn which is one of the major herbicides in agricultural discharges. While the MBR alone removes only 40% of ametryn at a hydraulic retention time of 7.8 h, the hybrid system removed ametryn to below detection levels.

Long-term drought aggravates instability of alpine grassland productivity to extreme climatic event.

The frequency and severity of extreme weather events are increasing and expected to increase more in the future, together with global change. However, how extreme events and global change factors interactively influence community structures and ecosystem processes is largely unknown. Here, we investigated the responses of the temporal stability and resilience of aboveground net primary productivity (ANPP) of an alpine meadow to an extreme flooding event under different treatments of experimental drought and clipping. We found that ecosystems that were exposed to drought treatments for 3 years significantly decreased the temporal stability of community productivity but increased resilience to flooding, whereas their resistance to or recovery from flooding did not change. Neither clipping nor its interaction with drought altered the responses of these community stability metrics to flooding. Drought treatments significantly decreased plant species richness and asynchrony and dominant species stability, leading to a decrease in temporal stability and an increase in resilience in response to the extreme flooding event. The study also revealed that the change in species asynchrony was the dominant impact pathway determining the responses of resilience and temporal stability to flooding. Our results highlight that alpine grassland that experiences a multiyear drought may aggravate the instability of community productivity to extreme climatic events by reducing species asynchrony.

Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets.

AIMS/HYPOTHESIS: Chronic hyperglycaemia promotes the progressive failure of pancreatic beta cells in patients with type 2 diabetes mellitus, a clinically highly relevant phenomenon known as glucotoxicity. The intracellular metabolic consequences of a chronically high availability of glucose in beta cells are, as yet, poorly understood in its full complexity. METHODS: An unbiased metabolite profiling analysis (GC-time-of-flight-MS) was used to identify the time course of core metabolite patterns in rat beta cell line INS-1E during exposure to high glucose concentrations and its relation to insulin expression. RESULTS: We report here that pentose phosphate pathway (PPP) metabolites accumulate remarkably during chronic but not acute glucose treatment, indicating altered processing of glucose through the pentose phosphate pathway. Subsequent functional studies in INS-1E cells and human islets revealed that a disturbance in this pathway contributes to decreases in insulin gene expression and a lack of glucose-stimulated insulin secretion. These effects were found to depend on the activation of extracellular-regulated-kinase (ERK1/2). Long-term inhibition of 6-phosphogluconic acid dehydrogenase resulted in accumulation of PPP metabolites, induced ERK1/2 activation independently of high glucose and impaired beta cell function. In turn, inhibition of ERK1/2 overstimulation during chronic glucose exposure partly inhibited metabolite accumulation and restored beta cell function. CONCLUSIONS/INTERPRETATION: Based on unbiased metabolite analyses, the data presented here provide novel targets, namely the inhibition of PPP metabolite accumulation towards the therapeutic goal to preserve and potentially improve beta cell function in diabetes.