Genetic improvement of phosphate-limited photosynthesis for high yield in rice.

Low phosphate (Pi) availability decreases photosynthesis, with phosphate limitation of photosynthesis occurring particularly during grain filling of cereal crops; however, effective genetic solutions remain to be established. We previously discovered that rice phosphate transporter OsPHO1;2 controls seed (sink) development through Pi reallocation during grain filling. Here, we find that OsPHO1;2 regulates Pi homeostasis and thus photosynthesis in leaves (source). Loss-of-function of OsPHO1;2 decreased Pi levels in leaves, leading to decreased photosynthetic electron transport activity, CO2 assimilation rate, and early occurrence of phosphate-limited photosynthesis. Interestingly, ectopic expression of OsPHO1;2 greatly increased Pi availability, and thereby, increased photosynthetic rate in leaves during grain filling, contributing to increased yield. This was supported by the effect of foliar Pi application. Moreover, analysis of core rice germplasm resources revealed that higher OsPHO1;2 expression was associated with enhanced photosynthesis and yield potential compared to those with lower expression. These findings reveal that phosphate-limitation of photosynthesis can be relieved via a genetic approach, and the OsPHO1;2 gene can be employed to reinforce crop breeding strategies for achieving higher photosynthetic efficiency.

Two ABCI family transporters, OsABCI15 and OsABCI16, are involved in grain-filling in rice.

Seed development is critical for plant reproduction and crop yield, with panicle seed-setting rate, grain-filling, and grain weight being key seed characteristics for yield improvement. However, few genes are known to regulate grain filling. Here, we identify two adenosine triphosphate (ATP)-binding cassette (ABC)I-type transporter genes, OsABCI15 and OsABCI16, involved in rice grain-filling. Both genes are highly expressed in developing seeds, and their proteins are localized to the plasma membrane and cytosol. Interestingly, knockout of OsABCI15 and OsABCI16 results in a significant reduction in seed-setting rate, caused predominantly by the severe empty pericarp phenotype, which differs from the previously reported low seed-setting phenotype resulting from failed pollination. Further analysis indicates that OsABCI15 and OsABCI16 participate in ion homeostasis and likely export ions between filial tissues and maternal tissues during grain filling. Importantly, overexpression of OsABCI15 and OsABCI16 enhances seed-setting rate and grain yield in transgenic plants and decreases ion accumulation in brown rice. Moreover, the OsABCI15/16 orthologues in maize exhibit a similar role in kernel development, as demonstrated by their disruption in transgenic maize. Therefore, our findings reveal the important roles of two ABC transporters in cereal grain filling, highlighting their value in crop yield improvement.

Interactions of CyMe4 -BTBP ligand with lanthanides and actinides: Insights from ESI-MS and DFT calculations.

Electrospray Ionization Mass Spectrometry (ESI-MS) technique and density functional theory (DFT) calculations were combined to study the formation of the complexes of lanthanides (Ln = La, Ce, Nd, Sm, Eu, Yb) and actinides (UO2 2+ , Th4+ ) with CyMe4 -BTBP (6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo-[1,2,4-]triazin-3-yl)-[2,2']bipyridine) to understand the mechanisms during the extraction process. Mass spectrometry titrations showed the formation of the complexation in acetonitrile. For lanthanides, only 1:2 complexes ([Ln(L)2 ]3+ , [Ln(L)2 (CH3 CN)]3+ ), [Ln(L)2 (NO3 )]2+ ) were found at low [Ln]/[L] concentration ratios, whereas the 1:1 complexes ([Ln(L)(NO3 )2 ]+ ) were observed when the [Ln]/[L] concentration ratio reached 1.0. For uranyl complexes, 1:1 complex ([UO2 L(NO3 )]+ ) was the only species within the measuring range. Th4+ complexes had two compositions: 1:1 and 1:2, in which 1:2 species was the dominant complex. Collision-induced dissociation (CID) was employed to characterize the fragmentation process. The fragmentation process was unfolded sequentially on both sides of CyMe4 -BTBP ligand with the loss of alkyl groups and cleavage of triazinyl rings. The CID results of CyMe4 -BTBP complexes revealed a slight difference depending on the metal center. The DFT calculations showed that the stable complexes formed in acetonitrile solution were consistent with the ESI-MS results.

[Phytoplankton Community Structure, Diversity, and Functional Groups in Urban River Under Different Black and Odorous Levels].

Phytoplankton community characteristics, diversity, and functional group analysis can respond to the environmental quality status of water bodies. To investigate the influence of urban river black odors on the phytoplankton community, from November 2020 to March 2021, 16 urban rivers in the Sichuan Basin were surveyed for water quality with 38 sampling points, and the degree of urban river black odor was evaluated based on the improved fuzzy mathematical model method and the k-mean principal color extraction method. The rivers were classified into four types:non-black and non-odorous, black and non-odorous, black and odorous, and black and odorous. The results showed that, with black and odorous water, the phytoplankton abundance increased from 1.329×105 cells·L-1 to 6.627×105 cells·L-1, and the dominant phytoplankton phylum decreased from Cyanophyta-Chlorophyta-Bacillariophyta to Cyanophyta. The phytoplankton biomass increased from 64.056 µg·L-1 to 120.465 µg·L-1, and the dominant phytoplankton phylum changed from Chlorophyta-Bacillariophyta type, adapted to a nutrient environment, to Pyrrophyta-Bacillariophyta-Cryptophyta type, adapted to an organic matter environment. The Shannon-Weaver diversity index decreased from 2.45 to 1.98, and Simpson's index decreased from 0.84 to 0.73. Twenty nine functional groups of phytoplankton were observed in the study area, and the growth strategy was reduced from S, R, C, CR, and CS to R with black and odorous water. In summary, phytoplankton indicators can better reflect the state of river black odor, and phytoplankton monitoring is a promising tool for urban river black odor management.

Four new lanostane triterpenoids featuring extended π-conjugated systems from the stems of Kadsura coccinea.

Four new 14(13 → 12)-abeolanostane triterpenoids featuring extended π-conjugated systems, kadcoccitanes E-H (1-4), were obtained from the stems of Kadsura coccinea through using a HPLC - UV-guided approach. Their structural and configurational determination was accomplished through extensive spectroscopic analysis coupled with quantum chemical calculations. Kadcoccitanes E-H were tested for their cytotoxic activities against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, SW-480) but none of them exhibited activities at the concentration 40 µM.

Novel function of a putative TaCOBL ortholog associated with cold response.

The plant COBRA protein family plays an important role in secondary cell wall biosynthesis and the orientation of cell expansion. The COBRA gene family has been well studied in Arabidopsis thaliana, maize, rice, etc., but no systematic studies were conducted in wheat. In this study, the full-length sequence of TaCOBLs was obtained by homology cloning from wheat, and a conserved motif analysis confirmed that TaCOBLs belonged to the COBRA protein family. qRT-PCR results showed that the TaCOBL transcripts were induced by abiotic stresses, including cold, drought, salinity, and abscisic acid (ABA). Two haplotypes of TaCOBL-5B (Hap5B-a and Hap5B-b), harboring one indel (----/TATA) in the 5' flanking region (- 550 bp), were found on chromosome 5BS. A co-dominant marker, Ta5BF/Ta5BR, was developed based on the polymorphism of the two TaCOBL-5B haplotypes. Significant correlations between the two TaCOBL-5B haplotypes and cold resistance were observed under four environmental conditions. Hap5B-a, a favored haplotype acquired during wheat polyploidization, may positively contribute to enhanced cold resistance in wheat. Based on the promoter activity analysis, the Hap5B-a promoter containing a TATA-box was more active than that of Hap5B-b without the TATA-box under low temperature. Our study provides valuable information indicating that the TaCOBL genes are associated with cold response in wheat.

An Enriched Environment Promotes Motor Function through Neuroprotection after Cerebral Ischemia.

Stroke seriously affects human health. Many studies have shown that enriched environment (EE) can promote functional recovery after stroke, but the intrinsic mechanisms remain unclear. In order to study the internal mechanisms of EE involved in functional recovery after ischemic stroke and which mechanism plays a leading role in the recovery of limb function after cerebral infarction, key proteins potentially involved in neuronal protection and synaptic remodeling in the ischemic penumbra have been investigated. In this study, adult C57BL/6 mice after permanent middle cerebral artery occlusion (pMCAO) were assigned to the EE and standard housing (SH) groups 3 days after operation. The EE house was spacious that contained a large variety of small toys; the SH was a normal sized cage. Sham-operated mice without artery occlusion were housed under standard conditions and were fed a normal diet. On days 3, 7, 14, and 21, postoperative motor functional recovery was tested using the modified neurological severity score (mNSS) and the Rotarod test. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) was examined by western blotting and immunofluorescence staining. The motor functional recovery (based on the mNSS and Rotarod test 3, 7, 14, and 21 days post operation) of mice in the EE group improved significantly compared to the SH group. The expression of GAP-43 and SYN and the ratio of Bcl-2/Bax were all upregulated in the EE group compared to the SH group. In addition, we also explored the relationship between neuronal protection and synaptic remodeling in the EE-mediated recovery of limb function after cerebral infarction by correlation analysis. Correlation analysis showed that compared with the increase of Bcl-2/Bax ratio, the increased expression of GAP-43 and SYN was more closely related to the recovery of limb function in ischemic mice. These data support the hypothesis that EE can promote the process of improvement of limb dysfunction induced by ischemic stroke, and this behavior restoration may, via promoting neuroprotection in the ischemic penumbra, be dependent on the regulation of the expression of GAP-43, SYN, Bcl-2, and Bax. A limitation of the study was that we only observed several representative key indicators of synaptic remodeling and neuronal apoptosis, without an in-depth study of the potential mechanisms involved.

[Influence factors of debilitating and nutritional risk on complications of primary hip replacement].

OBJECTIVE: To analyze relationship of debilitating and nutritional risk on complications of primary hip replacement, and risk factors of influence of complications of primary hip replacement. METHODS: Totally 100 patients who underwent hip replacement from January 2019 to January 2021 were retrospectively analyzed, including 36 males and 64 females, aged from 18 to 85 years old with an average of (73.82±4.04) years old. Postoperative frailty status was evaluated by modified frailty index, and nutritional status was evaluated by clinical biochemical indexes and NRS2002 nutritional risk assessment scale. One hundred patients were divided into frailty group and non-frailty group according to modified frailty index, 100 patients were divided into normal nutrition group and nutritional risk group according to nutritional status, and relationship between frailty, nutritional risk and complications after primary hip replacement was analyzed. RESULTS: There were significant differences in age, body mass index (BMI), complications and ASA grade between frailty group and non-frailty group(P<0.05). There were statistically significant differences in age, BMI, complications and ASA grade between normal nutrition group and nutritional risk group (P<0.05). Thirty-five patients occurred at least one postoperative complications, and the incidence of pulmonary infection was the highest, accounting for 34.29% (12/35). The second was urinary infection, accounting for 22.86%(8/35). Univariate Logistic regression analysis showed that age, BMI, ASA grade, complications, frailty and nutritional risk were the risk factors for postoperative complications. Multivariate Logistic regression analysis showed that complications, frailty and nutritional risk were independent factors affecting postoperative complications. CONCLUSION: Patients with comorbidities, frailty and nutritional risk could increase the incidence of complications. Timely assessment and identification of these patients in time, and formulation of targeted intervention measures have great clinical significance.

Efficacy and safety of traditional chinese medicine treatment for overweight and obese individuals: A systematic review and meta-analysis.

Background: The prevalence of obesity is increasing worldwide, causing a global health issue. Traditional Chinese medicine (TCM) used in treating overweight/obesity has been widely implemented in clinical practice, but its overall efficacy and safety remain unclear. This review aims to evaluate the effectiveness and safety of TCM based on randomized controlled trials (RCTs). Methods: A systematic review was conducted by searching PubMed, Cochrane Library, Web of Science, Embase, and Clinical Trails from their inception to March 2021. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The data were pooled for meta-analysis or presented narratively. Results: Twenty-five RCTs involving 1,947 participants were included. Compared with placebo or blank control, TCM preparations reduced Body Mass Index (BMI) [MD = -1.16; 95% confidence interval (CI) = -1.44, -0.89; I2 = 34%], reduced weight (MD = -2.53; 95% CI = -3.08, -1.99; I2 = 34%), reduced waist circumference (MD = -2.64; 95% CI = -3.42, -1.87; I2 = 0%), reduced hip circumference (MD = -3.48; 95% CI = -4.13, -2.83; I2 = 0%), reduced total cholesterol (TCHO) (MD = -10.45; 95% CI = -18.92, -1.98; I2 = 63%), reduced triglycerides (TG) (MD = -4.19; 95% CI = -6.35, -2.03; I2 = 25%), increased high-density lipoprotein (HDL) (MD = -3.60; 95% CI = -6.73, -0.47; I2 = 81%), reduced fasting blood glucose (FBG) (MD = -0.77; 95% CI = -1.24, -0.29; I2 = 91%). Glycated hemoglobin (HbA1c)、body fat rate、low-density lipoprotein (LDL) were not statistically significant. For people with hypertension, decreased systolic blood pressure (SBP) (MD = -5.27; 95% CI = -8.35, -2.19; I2 = 58%), decreased diastolic blood pressure (DBP) (MD = -4.30; 95% CI = -5.90, -2.69; I2 = 0%). For people with normal blood pressure, there was no significant change. There was no significant difference in liver function. Conclusion: It has been demonstrated that TCM preparations have good clinical efficacy and safety for overweight/obesity. TCM may be suitable for overweight/obesity in adult populations for its efficacy and safety of long-term treatment.

Enriched Environment-Induced Neuroprotection against Cerebral Ischemia-Reperfusion Injury Might Be Mediated via Enhancing Autophagy Flux and Mitophagy Flux.

Background: Enriched environment (EE) can protect the brain against damages caused by an ischemic stroke; however, the underlying mechanism remains elusive. Autophagy and mitochondria quality control are instrumental in the pathogenesis of ischemic stroke. In this study, we investigated whether and how autophagy and mitochondria quality control contribute to the protective effect of EE in the acute phase of cerebral ischemia-reperfusion injury. Methods: We exposed transient middle cerebral artery occlusion (tMCAO) mice to EE or standard condition (SC) for 7 days and then studied them for neurological deficits, autophagy and inflammation-related proteins, and mitochondrial morphology and function. Results: Compared to tMCAO mice in the SC group, those in the EE group showed fewer neurological deficits, relatively downregulated inflammation, higher LC3 expression, higher mitochondrial Parkin levels, higher mitochondrial fission factor dynamin-related protein-1 (Drp1) levels, lower p62 expression, and lower autophagy inhibitor mTOR expression. Furthermore, we found that the EE group showed a higher number of mitophagosomes and normal mitochondria, fewer mitolysosomes, and relatively increased mitochondrial membrane potential. Conclusion: These results suggested that EE enhances autophagy flux by inhibiting mTOR and enhances mitophagy flux via recruiting Drp1 and Parkin to eliminate dysfunctional mitochondria, which in turn inhibits inflammation and alleviates neurological deficits. Limitations. The specific mechanisms through which EE promotes autophagy and mitophagy and the signaling pathways that link them with inflammation need further study.

Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood via the Akt/p27 Signaling Pathway.

Objective: Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established. Methods: SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). The expression of p-Akt and p27 were measured by western blotting. The Morris water maze, novel object recognition test, and object location test were used to evaluate neurocognitive function 2-month-old rats. Results: Phosphorylation of Akt was inhibited, while p27 expression was enhanced after neonatal exposure to propofol. Propofol also inhibited proliferation of neural stem cells (NSCs) and decreased differentiation to neurons and astroglia. Moreover, the neurocognitive function in 2-month-old rats was weakened. Of significance, intra-hippocampal injection of the Akt activator, SC79, attenuated the inhibition of p-AKT and increase of p27 expression. SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation. The propofol-induced neurocognition deficit was also partially reversed by SC79. Conclusion: Taken together, these results suggest that neurogenesis is hindered by neonatal propofol exposure. Specifically, neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.

Comparisons of the Paleo-Mesoproterozoic large igneous provinces and black shales in the North China and North Australian cratons.

Comparisons of large igneous provinces (LIPs) and black shales from different cratons can provide important constraints on Precambrian paleogeographic reconstructions and a better understanding of the environmental effects of large-scale volcanic events. A comparison of intraplate mafic events mostly interpreted as LIPs or portions of LIPs (LIP fragments/remnants due to continental breakup or erosion) from the North China Craton (NCC) and North Australian Craton (NAC) shows good correlation in the age range from 1800 Ma to 1300 Ma, and four robust age matches at ca. 1790-1770 Ma, ca. 1730 Ma, ca. 1680-1670 Ma and ca. 1320 Ma have been identified. Most notably, the coeval ca. 1320 Ma Yanliao LIP in the eastern-northern NCC and the Derim Derim-Galiwinku LIP in the NAC are also characterized by similar field occurences and dominantly subalkaline tholeiitic basalts and intraplate geochemical compositions, and are interpreted as portions of the same LIP, separated by continental breakup. Subsequent to 1300 Ma, the NCC and NAC exhibit very different magmatic histories, indicating that separation of these two cratons occurred, likely subsequent to the ca. 1320 Ma LIP event. A comparison of Paleo-Mesoproterozoic black shales from the NCC and NAC provides further evidence for close connections between these regions during this period. Black shales of the Chuanlianggou Formation in the northern NCC and the Cuizhuang Formation in the southern NCC were deposited in the age range ca. 1650-1635 Ma and can be correlated with ca. 1640-1635 Ma black shales in the Barney Creek Formation of the NAC. Deposition of black shales within the Xiamaling Formation in the NCC and the Velkerri and Kyalla formations of the McArthur Basin in the NAC occurred synchronously at ca. 1380-1360 Ma. Our results from matching of LIP ages and black shales combined with paleomagnetic data show that the northern-northeastern margin of the NCC was connected to the northern margin of the NAC from ca. 1800 Ma to 1300 Ma. This long-lived late Paleoproterozoic to mid-Mesoproterozoic connection lasted for at least 500 million years until separation of the NCC from the NAC between ca. 1320 and ca. 1230-1220 Ma.

Effects of smartphone-based interventions and monitoring on bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Recently, there has been a range of studies about smartphone-based interventions and monitoring for reducing symptoms of bipolar disorder (BD). However, their efficacy for BD remains unclear. AIM: To compare the effect of smartphone-based interventions and monitoring with control methods in treating patients with BD. METHODS: A systematic literature search was performed on PubMed, Embase, Clinical trials, psycINFO, Web of Science, and Cochrane Library. Randomized clinical trials (RCTs) or single-group trials in which smartphone-based interventions and monitoring were compared with control methods or baseline in patients with symptoms of BD were included. Data were synthesized using a random-effects or a fixed-effects model to analyze the effects of psychological interventions and monitoring delivered via smartphone on psychiatric symptoms in patients with BD. The primary outcome measures were set for mania and depression symptoms. Subgroups were created to explore which aspects of smartphone interventions are relevant to the greater or lesser efficacy of treating symptoms. RESULTS: We identified ten articles, including seven RCTs (985 participants) and three single-group trials (169 participants). Analysis of the between-group study showed that smartphone-based interventions were effective in reducing manic [g = -0.19, 95% confidence interval (CI): -0.33 to -0.04, P = 0.01] and depressive (g = -0.28, 95%CI: -0.55 to -0.01, P < 0.05) symptoms. In within-group analysis, smartphone-based interventions significantly reduced manic (g = 0.17, 95%CI: 0.04 to 0.30, P < 0.01) and depressive (g = 0.48, 95%CI: 0.18 to 0.78) symptoms compared to the baseline. Nevertheless, smartphone-based monitoring systems significantly reduced manic (g = 0.27, 95%CI: 0.02 to 0.51, P < 0.05) but not depressive symptoms. Subgroup analysis indicated that the interventions with psychoeducation had positive effects on depressive (g = -0.62, 95%CI: -0.81 to -0.43, P < 0.01) and manic (g = -0.24, 95%CI: -0.43 to -0.06, P = 0.01) symptoms compared to the controlled conditions, while the interventions without psychoeducation did not (P > 0.05). The contacts between therapists and patients that contributed to the implementation of psychological therapy reduced depression symptoms (g = -0.47, 95%CI: -0.75 to -0.18, P = 0.01). CONCLUSION: Smartphone-based interventions and monitoring have a significant positive impact on depressive and manic symptoms of BD patients in between-group and within-group analysis.

Gibberellin repression of axillary bud formation in Arabidopsis by modulation of DELLA-SPL9 complex activity.

The formation of lateral branches has an important and fundamental contribution to the remarkable developmental plasticity of plants, which allows plants to alter their architecture to adapt to the challenging environment conditions. The Gibberellin (GA) phytohormones have been known to regulate the outgrowth of axillary meristems (AMs), but the specific molecular mechanisms remain unclear. Here we show that DELLA proteins regulate axillary bud formation by interacting and regulating the DNA-binding ability of SQUAMOSA-PROMOTER BINDING PROTEIN LIKE 9 (SPL9), a microRNA156-targeted squamosa promoter binding protein-like transcription factor. SPL9 participates in the initial regulation of axillary buds by repressing the expression of LATERAL SUPPRESSOR (LAS), a key regulator in the initiation of AMs, and LAS contributes to the specific expression pattern of the GA deactivation enzyme GA2ox4, which is specifically expressed in the axils of leaves to form a low-GA cell niche in this anatomical region. Nevertheless, increasing GA levels in leaf axils by ectopically expressing the GA-biosynthesis enzyme GA20ox2 significantly impaired axillary meristem initiation. Our study demonstrates that DELLA-SPL9-LAS-GA2ox4 defines a core feedback regulatory module that spatially pattern GA content in the leaf axil and precisely control the axillary bud formation in different spatial and temporal.

The light-dependent lethal effects of 1,2-benzisothiazol-3(2H)-one and its biodegradation by freshwater microalgae.

As 1,2-benzisothiazol-3(2H)-one (BIT) has been widely used in high concentrations for microbial growth control in many domestic and industrial processes, its potential eco-risk should be assessed. This study investigated the interaction between BIT and microalgae in aquatic environment as the mechanism of BIT lethal effect on microalgae was unclear and whether microalgae could efficiently remove BIT was unknown. It was found that Chlorella vulgaris could be killed by high concentrations of BIT, and this lethal effect was strongly enhanced when exposed to light. Inhibition of photosystem II electron transport followed by a decrease in cellular chlorophyll led to serious damage to algal photosynthesis. The excess accumulation of reactive oxygen species caused by the photosynthetic damage under light further increased the oxidative damage and promoted cell death. Under dark condition, however, the algae could tolerate higher BIT concentrations. BIT could be efficiently removed when the growth of Scenedesmus sp. LX1 was not completely inhibited. With an initial concentration of 4.5 mg/L, over 99% of BIT was removed during 168 hour cultivation. Microalgal biodegradation was the primary reason for this removal, and the contributions of BIT hydrolytic/photolytic degradation, microalgal growth, photosynthesis and sorption were negligibly small. These results pointed to the potential application of microalgae for efficient BIT removal from wastewater.

Regio- and Stereoselective Alkenylation of Allenoates with gem-Difluoroalkenes: Facile Access to Fluorinated 1,4-Enynes Bearing an All-Carbon Quaternary Center.

A regio- and stereoselective synthesis of fluorinated 1,4-enynes bearing an all-carbon quaternary center at the propargylic position is developed. The synthesis starts from readily available allenoates and gem-difluoroalkenes and proceeds via a key alkynylenolate intermediate following a nucleophilic addition/ß-F elimination. This reaction occurs under mild reaction conditions with good tolerance to a variety of functional groups. Synthetic utility is demonstrated by further transformations of the products. Furthermore, the reaction can also be applied for the synthesis of α-alkenyl allenoates by using 3,3-disubstituted allenoates.

Overexpression of hepatocyte nuclear factor 4α in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/ß-catenin signaling pathway downregulation.

Mesenchymal stem cells (MSCs) hold promise as cellular vehicles for the delivery of therapeutic gene products because they can be isolated, expanded, and genetically modified in vitro and possess tumor-oriented homing capacity in vivo. (1) Hepatocyte nuclear factor 4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis (HCC). (2,3) We have previously demonstrated that overexpression of HNF4α activates various hepatic-specific genes and enhances MSC differentiation. (4) However, the extent that overexpression of HNF4α in MSCs influences HCC progression has yet to be examined. Here we sought to investigate what effect MSCs overexpressing HNF4α (MSC-HNF4α) have on human hepatoma cells in vitro and in vivo. Conditioned medium collected from in vitro MSC-HNF4α cultures significantly inhibited hepatoma cell growth and metastasis compared with controls. Additionally, nude mice administered MSC-HNF4α exhibited significantly smaller tumors compared with controls in vivo. Immunoblot analysis of HCC cells treated with MSC-HNF4α displayed downregulated ß-catenin, cyclinD1, c-Myc, MMP2 and MMP9. Taken together, our results demonstrate that MSC-HNF4α inhibits HCC progression by reducing hepatoma cell growth and metastasis through downregulation of the Wnt/ß-catenin signaling pathway.

ER-α36, a novel variant of ERα, is involved in the regulation of Tamoxifen-sensitivity of glioblastoma cells.

Although accumulating evidence has confirmed that adjuvant Tamoxifen (TAM) treatment is able to sensitize glioblastoma cells to radiotherapy and inhibit their proliferation, TAM is not a suitable treatment for all types of glioblastoma cells; furthermore, long-term TAM usage may lead to TAM resistance. Therefore, understanding the underlying molecular mechanism of TAM resistance is necessary in order to improve TAM clinical therapy and the quality of life of patients suffering from glioblastomas. In this study, the significance of ER-α36 to TAM resistance in glioblastoma cells was examined. First, an analysis of ER-α36 expression in two glioblastoma cell lines U87-MG and U251, showed that ER-α36 was anchored to the cytoplasmic membrane of these cells via Caveolin-1. Subsequent experiments investigating the mechanism of TAM-induced inhibition of U87-MG cell growth showed that TAM exerts its effect by inducing apoptosis via a down-regulation of Survivin expression and an up-regulation of Caspase-3 expression. Furthermore, TAM also arrested the cell cycle at S-phase. However, when U87-MG cells were preconditioned with an ER-α36-specific agonist, IC162, this neutralized TAM-induced inhibition of cell growth. This contrasted with the effect of ER-α36 depletion by RNAi, which enhanced TAM-induced inhibition of cell growth. These findings suggest that resistance to TAM involves ER-α36, which probably acts as a negative regulator of TAM-induced inhibition of glioblastoma cell growth. These findings provide a novel insight into the basis of TAM resistance during glioblastoma therapy and a further study is underway to reveal more about the specific molecular mechanisms associated with ER-α36-mediated TAM resistance.

Caveolin-1 and glucose transporter 4 involved in the regulation of glucose-deprivation stress in PC12 cells.

Recent evidence suggests that caveolin-1 (Cav-1), the major protein constituent of caveolae, plays a prominent role in neuronal nutritional availability with cellular fate regulation besides in several cellular processes such as cholesterol homeostasis, regulation of signal transduction, integrin signaling and cell growth. Here, we aimed to investigate the function of Cav-1 and glucose transporter 4 (GLUT4) upon glucose deprivation (GD) in PC12 cells. The results demonstrated firstly that both Cav-1 and GLUT4 were up-regulated by glucose withdrawal in PC12 cells by using Western blot and laser confocal technology. Also, we found that the cell death rate, mitochondrial membrane potential (MMP) and intracellular free Ca(2+) concentration ([Ca(2+)]i) were also respectively changed followed the GD stress tested by CCK8 and flow cytometry. After knocking down of Cav-1 in the cells by siRNA, the level of [Ca(2+)]i was increased, and MMP was reduced further in GD-treated PC12 cells. Knockdown of Cav-1 or methylated-ß-Cyclodextrin (M-ß-CD) treatment inhibited the expression of GLUT4 protein upon GD. Additionally, we found that GLUT4 could translocate from cytoplasm to cell membrane upon GD. These findings might suggest a neuroprotective role for Cav-1, through coordination of GLUT4 in GD.

The Rebirth of Waste Cooking Oil to Novel Bio-based Surfactants.

Waste cooking oil (WCO) is a kind of non-edible oil with enormous quantities and its unreasonable dispose may generate negative impact on human life and environment. However, WCO is certainly a renewable feedstock of bio-based materials. To get the rebirth of WCO, we have established a facile and high-yield method to convert WCO to bio-based zwitterionic surfactants with excellent surface and interfacial properties. The interfacial tension between crude oil and water could reach ultra-low value as 0.0016 mN m(-1) at a low dosage as 0.100 g L(-1) of this bio-based surfactant without the aid of extra alkali, which shows a strong interfacial activity and the great potential application in many industrial fields, in particular, the application in enhanced oil recovery in oilfields in place of petroleum-based surfactants.