ALTA: a simple nutritional prognostic score for patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Malnutrition, despite being a common complication, is often neglected in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). The objective of this study was to develop a simplified nutritional prognostic score to accurately predict mortality in HBV-ACLF patients. Methods: In this multicenter retrospective study, clinical data from 530 HBV-ACLF patients were used to create a new prognostic score, which was then validated in two external cohorts (n = 229 and 248). Results: Four independent factors were significantly associated with 28-day mortality in HBV-ACLF patients, forming a novel prognostic score (ALTA score = 0.187 × age-0.849 × lymphocyte count-2.033 × total cholesterol-0.148 × albumin-0.971). Notably, the AUROC of ALTA score for 28/90-day mortality (0.950/0.967) were significantly higher than those of three other ACLF prognostic scores (COSSH-ACLF II, 0.864/0.734; MELD, 0.525/0.488; MELD-Na, 0.546/0.517; all P < 0.001), and three known nutritional scores (CONUT, 0.739/0.861; OPNI, 0.279/0.157; NRS-2002, 0.322/0.286; all P < 0.001). The prediction error rates of ALTA score for 28-day mortality were significantly lower than COSSH-ACLF II (7.3%), MELD (14.4%), MELD-Na (12.7%), CONUT (9.0%), OPNI (30.6%), and NRS2002 (34.1%) scores. Further classifying ALTA score into two strata, the hazard ratios of mortality at 28/90 days were notably increased in the high-risk groups compared to the low-risk group (15.959 and 5.740). These results were then validated in two external cohorts. Conclusion: ALTA, as a simplified nutritional prognostic score for HBV-ACLF, demonstrates superiority over the COSSH-ACLF II and other scores in predicting short-term mortality among HBV-ACLF patients. Therefore, it may be used to guide clinical management, particularly in primary care settings.

BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome.

AIMS: Neuroinflammation and pyroptosis are key mediators of cerebral ischemia/reperfusion (I/R) injury-induced pathogenic cascades. BRCC3, the human homolog of BRCC36, is implicated in neurological disorders and plays a crucial role in neuroinflammation and pyroptosis. However, its effects and potential mechanisms in cerebral I/R injury in mice are unclear. METHODS: Cellular localization of BRCC3 and the interaction between BRCC3 and NLRP6 were assessed. Middle cerebral artery occlusion/reperfusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were established in mice and HT22 cells, respectively, to simulate cerebral I/R injury in vivo and in vitro. RESULTS: BRCC3 protein expression peaked 24 h after MCAO and OGD/R. BRCC3 knockdown reduced the inflammation and pyroptosis caused by cerebral I/R injury and ameliorated neurological deficits in mice after MCAO. The effects of BRCC3 on inflammation and pyroptosis may be mediated by NLRP6 inflammasome activation. Moreover, both BRCC3 and its N- and C-terminals interacted with NLRP6, and both BRCC3 and its terminals reduced NLRP6 ubiquitination. Additionally, BRCC3 affected the interaction between NLRP6 and ASC, which may be related to inflammasome activation. CONCLUSION: BRCC3 shows promise as a novel target to enhance neurological recovery and attenuate the inflammatory responses and pyroptosis caused by NLRP6 activation in cerebral I/R injury.

Intestinal metabolite UroB alleviates cerebral ischemia/reperfusion injury by promoting competition between TRIM65 and TXNIP for binding to NLRP3 inflammasome in response to neuroinflammation.

Our previous research suggests that targeting NLRP3 inflammasomes holds promise for mitigating cerebral ischemia/reperfusion injury. The gut metabolite Urolithin B (UroB) has been shown to inhibit the neuroinflammation. However, the specific role of UroB in cerebral ischemia/reperfusion injury and its potential impact on NLRP3 inflammasome remain unclear. In this study, acute stroke was simulated using the MCAO model in male Sprague-Dawley rats. UroB was intraperitoneally administered after 1 h of reperfusion. The effects of UroB on brain tissue were evaluated, including infarct volume, brain edema, and neurobehavioral changes. Western blotting and immunofluorescence were performed to investigate the effect of UroB on inflammation-related proteins. Furthermore, TRIM65 knockdown and TXNIP overexpression experiments elucidated the role of UroB in NLRP3 inflammasome activation. The ( demonstrate the neuroprotective effect of UroB in acute stroke, reducing brain tissue damage and improving motor function. Mechanistically, UroB modulated neuroinflammation by influencing TXNIP and TRIM65 protein expression, as well as competitive binding to the NLRP3 inflammasome, attenuating cerebral ischemia/reperfusion injury. In conclusion, the potential of UroB as a protective agent against cerebral ischemia/reperfusion injury in acute stroke stands out as it regulates TRIM65 and TXNIP competitive binding to the NLRP3 inflammasome. These findings suggest that UroB is a promising drug candidate for the treatment of acute stroke.

NLRP6 deficiency inhibits neuroinflammation and ameliorates brain injury in ischemic stroke by blocking NLRs inflammasomes activation through proteasomal degradation of pro-caspase-1.

Innate inflammation is crucial for ischemic stroke development. NLRP6, a nucleotide-binding and oligomerization domain-like receptors (NLRs) family member, regulates innate inflammation. Whether NLRP6 regulates neurological damage and neuroinflammation during ischemic stroke remains unclear. We report that NLRP6 is abundantly expressed in microglia and significantly upregulated in the ischemic brain. The brain injury severity was alleviated in NLRP6-deficient mice after ischemic stroke, as evidenced by reduced cerebral infarct volume, decreased neurological deficit scores, improved histopathological morphological changes, ameliorated neuronal denaturation, and relief of sensorimotor dysfunction. In the co-culture OGD/R model, NLRP6 deficiency prevented neuronal death and attenuated microglial cell injury. NLRP6 deficiency blocked several NLRs inflammasomes' activation and abrogated inflammasome-related cytokine production by decreasing the expression of the common effector pro-caspase-1. NLRP6 deficiency reduced pro-caspase-1's protein level by inducing proteasomal degradation. These findings confirm the neuroprotective role of NLRP6 deficiency in ischemic stroke and its underlying regulation mechanism in neuroinflammation and provide a potential therapeutic target for ischemic stroke.

Energy performance of an innovative bifacial photovoltaic sunshade (BiPVS) under hot summer and warm winter climate.

The bi-facial photovoltaic sunshade (BiPVS) is an innovative solution that utilizes vertically mounted bi-facial photovoltaic modules to provide shading. The BiPVS is capable of converting incident solar radiation into electricity on both the front and rear sides of the module, resulting in higher electrical efficiency compared to traditional mono-facial PV sunshades. The BiPVS has great potential as a sustainable solution for building shading and energy generation, which allows for improved indoor light/thermal environment and building energy efficiency. In this study, the bi-facial photovoltaic sunshade (BiPVS) was implemented in an office under typical hot summer and warm winter climate of Shenzhen, China. The energy performance of the BiPVS was analyzed using Energyplus. The comprehensive building energy saving was evaluated by comparing the energy consumption of the office with and without the BiPVS. Results showed that the total annual photovoltaic power generation was 133.19 kWh, while the comprehensive building energy savings were 159.65 kWh. Additionally, carbon dioxide emissions were reduced by 83.29 kgCO2 per year. The proposed method can help optimize the design parameters of BiPVS according to specific climate conditions, building types, and orientation, and contribute to the development of high-efficiency BIPV technology and support efforts towards carbon neutrality.

Wave reflection quantification analysis and personalized flow wave estimation based on the central aortic pressure waveform.

Pulse wave reflections reflect cardiac afterload and perfusion, which yield valid indicators for monitoring cardiovascular status. Accurate quantification of pressure wave reflections requires the measurement of aortic flow wave. However, direct flow measurement involves extra equipment and well-trained operator. In this study, the personalized aortic flow waveform was estimated from the individual central aortic pressure waveform (CAPW) based on pressure-flow relations. The separated forward and backward pressure waves were used to calculate wave reflection indices such as reflection index (RI) and reflection magnitude (RM), as well as the central aortic pulse transit time (PTT). The effectiveness and feasibility of the method were validated by a set of clinical data (13 participants) and the Nektar1D Pulse Wave Database (4,374 subjects). The performance of the proposed personalized flow waveform method was compared with the traditional triangular flow waveform method and the recently proposed lognormal flow waveform method by statistical analyses. Results show that the root mean square error calculated by the personalized flow waveform approach is smaller than that of the typical triangular and lognormal flow methods, and the correlation coefficient with the measured flow waveform is higher. The estimated personalized flow waveform based on the characteristics of the CAPW can estimate wave reflection indices more accurately than the other two methods. The proposed personalized flow waveform method can be potentially used as a convenient alternative for the measurement of aortic flow waveform.

Improving Agrobacterium tumefaciens-Mediated Genetic Transformation for Gene Function Studies and Mutagenesis in Cucumber (Cucumis sativus L.).

In the post-genomics era, Agrobacterium tumefaciens-mediated genetic transformation is becoming an increasingly indispensable tool for characterization of gene functions and crop improvement in cucumber (Cucumis sativus L.). However, cucumber transformation efficiency is still low. In this study, we evaluated the effects of several key factors affecting the shoot-regeneration rate and overall transformation efficiency in cucumber including genotypes, the age and sources of explants, Agrobacterium strains, infection/co-cultivation conditions, and selective agents. We showed that in general, North China cucumbers exhibited higher shoot-regeneration rate than US pickling or slicing cucumbers. The subapical ground meristematic regions from cotyledons or the hypocotyl had a similar shoot-regeneration efficiency that was also affected by the age of the explants. Transformation with the Agrobacterium strain AGL1 yielded a higher frequency of positive transformants than with GV3101. The antibiotic kanamycin was effective in selection against non-transformants or chimeras. Optimization of various factors was exemplified with the development of transgenic plants overexpressing the LittleLeaf (LL) gene or RNAi of the APRR2 gene in three cucumber lines. The streamlined protocol was also tested in transgenic studies in three additional genes. The overall transformation efficiency defined by the number of verified transgenic plants out of the number of seeds across multiple experiments was 0.2-1.7%. Screening among T1 OE transgenic plants identified novel, inheritable mutants for leaf or fruit color or size/shape, suggesting T-DNA insertion as a potential source of mutagenesis. The Agrobacterium-mediated transformation protocol from this study could be used as the baseline for further improvements in cucumber transformation.

IKZF3 modulates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation.

Neuroinflammation is a key mediator to the pathogenic cascades induced by cerebral ischemia-reperfusion (I/R) injury. IKZF3, a key zinc finger transcription factor in the Ikaros family, has already been shown to modulate a wide range of cell functions and the production of inflammatory mediators. However, the effects of IKZF3 on inflammation and the potential mechanism after cerebral I/R injury remain unclear. In this study, we evaluated the effect of IKZF3 on HT-22 cells under oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro and in mice with MACO in vivo. We found that IKZF3 expression peaked at 12 h after MCAO and OGD/R, and there was high expression of IKZF3 in brain tissues and HT-22 cells. IKZF3 knockdown exacerbated the damage by OGD-induced HT-22 cells injury and MCAO-induced brain injury in mice by regulating the production of inflammatory factors, which promoted the phosphorylation and nuclear transfer of NF-ĸB and may bind with NF-ĸB-p65 in vivo and in vitro. Our results suggested that IKZF3 may provide a new target in improve neurological recovery and reducing neuroinflammation after cerebral I/R injury.

[Quantitative analysis of the effect of contact pressure on the reflection characteristics of radial pressure wave].

The radial artery pulse wave contains a wealth of physiological and pathological information about the human body, and non-invasive studies of the radial artery pulse wave can assess arterial vascular elasticity in different age groups.The piezoelectric pulse wave transducers were used to non-invasively acquire radial artery pulse waves at different contact pressures in young and middle-aged and elderly populations. The radial artery waveforms were decomposed using a triangular blood flow model fitting method to obtain forward and reflected waves and calculate reflection parameters. Finally a correlation analysis and regression analysis of the contact pressure Psensor with the reflection parameters was carried out. The results showed that the reflection parameters RM, RI and Rd had a strong negative correlation with Psensor in both types of subjects, and the correlation coefficients and slopes of the regression curves were significantly different between the two types of subjects (P<0.05). Based on the results of this study, excessive contact pressure on the transducer should be avoided when detecting radial artery reflection waves in clinical practice. The results also show that the magnitude of the slope of the regression curve between the reflection parameters and the transducer contact pressure may be a potentially useful indicator for quantifying the elastic properties of the vessel.

Sigma factor binding protein 1 (CsSIB1) is a putative candidate of the major-effect QTL dm5.3 for downy mildew resistance in cucumber (Cucumis sativus).

KEY MESSAGE: The dm5.3 major-effect QTL in cucumber encodes a homolog of Arabidopsis sigma factor binding protein 1 (CsSIB1). CsSIB1 positively regulates defense responses against downy mildew in cucumber through the salicylic acid (SA) biosynthesis/signaling pathway. Downy mildew (DM) caused by the oomycete pathogen Pseudoperonospora cubensis is an important disease of cucumber and other cucurbits. Our knowledge on molecular mechanisms of DM resistance is still limited. In this study, we reported identification and functional characterization of the candidate gene for the major-effect QTL, dm5.3 for DM resistance originated from PI 197088. The dm5.3 QTL was Modelized through marker-assisted development of near isogenic lines (NILs). NIL-derived segregating populations were used for fine mapping which narrowed the dm5.3 locus down to a 144 kb region. Based on multiple lines of evidence, we show that CsSIB1 (CsGy5G027140) that encodes the VQ motif-containing sigma factor binding protein 1 as the most likely candidate for dm5.3. Local association analysis identified a haplotype consisting of 7 SNPs inside the coding and promoter region of CsSIB1 that was associated with DM resistance. Expression of CsSIB1 was up-regulated with P. cubensis infection. Transcriptome profiling of NILs in response to P. cubensis inoculation revealed key players and associated gene networks in which increased expression of CsSIB1 antagonistically promoted salicylic acid (SA) but suppressed jasmonic acid (JA) biosynthesis/signaling pathways. Our work provides novel insights into the function of CsSIB1/dm5.3 as a disease resistance (R) gene. The roles of sigma factor binding protein genes in pathogen defense in cucumber were also discussed.

Functional copy number variation of CsSHINE1 is associated with fruit skin netting intensity in cucumber, Cucumis sativus.

Fruit skin netting in cucumber (Cucumis sativus) is associated with important fruit quality attributes. Two simply inherited genes H (Heavy netting) and Rs (Russet skin) control skin netting, but their molecular basis is unknown. Here, we reported map-based cloning and functional characterization of the candidate gene for the Rs locus that encodes CsSHINE1 (CsSHN1), an AP2 domain containing ethylene-responsive transcription factor protein. Comparative phenotypic analysis in near-isogenic lines revealed that fruit with netted skin had different epidermal structures from that with smooth skin including thicker cuticles, smaller, palisade-shaped epidermal and sub-epidermal cells with heavily suberized and lignified cell walls, higher peroxidase activities, which suggests multiple functions of CsSHN1 in regulating fruit skin netting and epidermal cell patterning. Among three representative cucumber inbred lines, three haplotypes at three polymorphic sites were identified inside CsSHN1: a functional copy in Gy14 (wild type) with light fruit skin netting, a copy number variant with two tandemly arrayed functional copies in WI7120 with heavy skin netting, and a loss-of-function copy in 9930 with smooth skin. The expression level of CsSHN1 in fruit exocarp of three lines was positively correlated with the skin netting intensity. Comparative analysis between cucumber and melon revealed conserved and divergent genetic mechanisms underlying fruit skin netting/reticulation that may reflect the different selection histories in the two crops. A discussion was made on genetic basis of fruit skin netting in the context of natural and artificial selections of fruit quality-related epidermal features during cucumber breeding.

Platonin protects against cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasomes via BNIP3/LC3 signaling mediated autophagy.

Studies have found that Platonin has neuroprotective effect, but its molecular mechanism needs further study. We found that at the early stage of cerebral ischemia/reperfusion injury, Platonin treatment significantly reduced cerebral infarct lesions, improved neurological scores, and exerted neuroprotective effects. Our group has shown that NLRP3 inflammasomes activation is required to mediate neuronal injury during cerebral ischemia /reperfusion injury. The brain protective effect of Platonin is related to its ability to effectively regulate autophagy and NLRP3 inflammasomes-derived inflammation. Platonin treatment effectively induced autophagy (LC3II/I, p62) and reduced NLRP3 inflammasomes activation(NLRP3, cleaved-IL-1ß，cleaved-IL-18, cleaved-caspase1). However, 3-MA (15 mg/kg) treatment downregulated the inhibitory effect of Platonin on NLRP3 inflammasomes. We also studied the location of BNIP3 in Platonin-mediated neuroprotection and found that Platonin induced the expression of autophagic protein BNIP3 and enhanced the co-immunoprecipitation of BNIP3 with LC3, and double-labeled immunofluorescence also showed enhanced co-localization of BNIP3 with LC3. Finally, si-BNIP3 transfection attenuated the co localization of BNIP3 with LC3, decreased the autophagy activity to a certain extent and blocked the inhibition of NLRP3 inflammasomes-derived inflammation by Platonin. This study demonstrated that Platonin may play a neuroprotection role in cerebral I / R injury by inhibiting NLRP3 inflammasomes activation through upregulating autophagy via BNIP3 / LC3 pathway.

6-Gingerol protects against cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome and apoptosis via TRPV1 / FAF1 complex dissociation-mediated autophagy.

BACKGROUND: Our previous studies demonstrated that autophagy alleviates cerebral I/R injury by inhibiting NLRP3 inflammasome-mediated inflammation. 6-Gingerol, a phenolic compound extracted from ginger, was reported to possess potent antiapoptotic and anti-inflammatory activities and is associated with autophagy. However, the effects of 6-Gingerol in cerebral I/R injury have not been elucidated, and whether they involve autophagy-induced NLRP3 inflammasome inhibition remains unclear. METHODS: Adult male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion for 24 h. 6-Gingerol and 3-methyladenine (3-MA) were injected intraperitoneally, and si-TRPV1 was injected via the lateral ventricle. Cerebral infarct volume, brain edema, neurological deficits, HE and Nissl were used to evaluate the morphological and functional changes of brain tissue, respectively. TRPV1, FAF1, autophagy related (LC3II/I, P62, Beclin1), inflammation related (NLRP3, cleaved-caspase-1, caspase-1, cleaved-IL-1ß, IL-1ß, cleaved-IL-18, IL-18) and apoptosis related (Bcl-2, Bax, cleaved-caspase-3) proteins were assessed by Western blot, immunofluorescence staining and coimmunoprecipitation, respectively. Enzyme linked immunosorbent assay (ELISA) was used to evaluate the changes in the expression levels of interleukin-1 (IL-1ß) and interleukin-18(IL-18), respectively. The degree of neuronal apoptosis was evaluated by TUNEL staining. Neuronal ultrastructure was examined by transmission electron microscopy. RESULT: 6-Gingerol treatment significantly reduced cerebral infarct volume, improved brain edema and neurological scores, and reversed brain histomorphological damage after I/R injury. In addition, 6-Gingerol significantly reduced NLRP3 inflammasome-derived inflammation and neuronal apoptosis and upregulated autophagy. The autophagy inhibitor 3-MA rescued the effects of 6-Gingerol on the NLRP3 inflammasome and apoptosis. Moreover, the findings illustrated that 6-Gingerol inhibited autophagy-induced NLRP3 inflammasome activation and apoptosis through the dissociation of TRPV1 from FAF1. CONCLUSION: In brief, 6-Gingerol exerts antiapoptotic and anti-inflammatory effects via TRPV1/FAF1 complex dissociation-mediated autophagy during cerebral I/R injury. Therefore, 6-Gingerol may be an effective drug for the treatment of I/R injury.

BRCC3 promotes activation of the NLRP6 inflammasome following cerebral ischemia/reperfusion (I/R) injury in rats.

NOD-like receptor family pyrin domain containing 6 (NLRP6), a novel member of the NLR family, has been confirmed to have an inflammasome-dependent proinflammatory effect in cerebral ischemia/reperfusion injury. NLRP6 assembles a multimeric inflammasome complex comprising the adaptor ASC and the effector pro-caspase-1 to mediate the activation of caspase-1. The molecular mechanism regulating activation of the NLRP6 inflammasome remains unclear. Previous studies have shown that BRCA1-BRCA2-containing complex subunit 3 (BRCC3), a JAMM domain-containing Zn2+ metalloprotease deubiquitinating enzyme, participates in a variety of cellular activities. In this study, we found that BRCC3 expression was increased in the middle cerebral artery occlusion (MCAO) model. BRCC3 siRNA could reduce nerve damage and inflammation. Interestingly, the result of co-immunoprecipitation showed that the interaction between BRCC3 and NLRP6 was enhanced after model, and the result of immunofluorescence showed that the co-localization of BRCC3 and NLRP6 was increased. At the same time, the expression of NLRP6, cleavated-caspase-1 and IL-1ß was decreased after BRCC3 interference. These results illustrate a regulatory mechanism involving the BRCC3-NLRP6 pathway and highlight NLRP6 as a potential therapeutic target for inflammatory diseases.

Syringin exerts neuroprotective effects in a rat model of cerebral ischemia through the FOXO3a/NF-κB pathway.

Inflammation plays an important role in the pathogenesis of cerebral ischemia. Syringin (SYR) is an active substance isolated from Acanthopanax senticosus plants, and possesses anti-inflammatory and neuroprotective properties. However, its effects on cerebral ischemic injury, as well as the underlying molecular events, are still unclear. The purpose of this study was to investigate the effect of SYR in a rat model of cerebral ischemia and address the related molecular mechanism. A middle cerebral artery occlusion/reperfusion model (MCAO) was used to simulate ischemic injury. SYR treatment clearly reduced the infarct volume, decreased cerebral water content, improved the neurological score, and attenuated neuronal death. Moreover, SYR decreased the expression of NF-κB, IL-1ß, IL-6, TNF-α, and MPO, promoted FOXO3a phosphorylation and cytoplasmic retention, and inhibited the nuclear translocation of NF-κB. FOXO3a knockdown by RNA interference significantly prevented SYR-induced inhibition of NF-κB-mediated inflammation. Confocal microscopy revealed that SYR reduced NF-κB translocation to the nucleus, and FOXO3a silencing reversed this effect. Finally, immunofluorescence and CO-IP experiments showed that SYR promoted the interaction between FOXO3a and NF-κB. In conclusion, SYR exerted a protective effect against brain I/R injury by reducing the inflammation accompanying cerebral ischemia. This effect was mediated by the FOXO3a /NF-κB pathway.

Theranostic Nanomedicine for Synergistic Chemodynamic Therapy and Chemotherapy of Orthotopic Glioma.

Glioma is a common primary brain malignancy with a poor prognosis. Chemotherapy is the first-line treatment for brain tumors but low efficiency of drugs in crossing the blood-brain barrier (BBB) and drug resistance related to tumor hypoxia thwart its efficacy. Herein, a theranostic nanodrug (iRPPA@TMZ/MnO) is developed by incorporating oleic acid-modified manganese oxide (MnO) and temozolomide (TMZ) into a polyethylene glycol-poly(2-(diisopropylamino)ethyl methacrylate-based polymeric micelle containing internalizing arginine-glycine-aspartic acid (iRGD). The presence of iRGD provides the nanodrug with a high capacity of crossing the BBB and penetrating the tumor tissue. After accumulation in glioma, the nanodrug responds to the tumor microenvironment to simultaneously release TMZ, Mn2+, and O2. The released TMZ induces tumor cell apoptosis and the released Mn2+ causes intracellular oxidative stress that kill tumor cells via a Fenton-like reaction. The O2 produced in situ alleviates tumor hypoxia and enhances the chemotherapy/chemodynamic therapeutic effects against glioma. The Mn2+ can also serve as a magnetic resonance imaging (MRI) contrast agent for tumor imaging during therapy. The study demonstrates the great potential of this multifunctional nanodrug for MRI-visible therapy of brain glioma.

I6P7 peptide modified superparamagnetic iron oxide nanoparticles for magnetic resonance imaging detection of low-grade brain gliomas.

Glioma, the most severe primary brain malignancy, has very low survival rates and a high level of recurrence. Nowadays, conventional treatments for these patients are suffering a similar plight owing to the distinctive features of the malignant gliomas, for example chemotherapy is limited by the blood-brain barrier while surgery and radiation therapy are affected by the unclear boundaries of tumor from normal tissue. In the present study, a novel superparamagnetic iron oxide (SPIO) nanoprobe for enhanced T2-weighted magnetic resonance imaging (MRI) was developed. A frequently used MRI probe, SPIO nanoparticles, was coated with a silica outer layer and for the first time was covalently modified with interleukin-6 receptor targeting peptides (I6P7) to promote transportation through the blood-brain barrier and recognition of low-grade gliomas. The efficiency of transcytosis across the blood-brain barrier was examined in vitro using a transwell invasion model and in vivo in nude mice with orthotopic low-grade gliomas. The targeting nanoprobe showed significant MRI enhancement and has potential for use in the diagnosis of low-grade gliomas.

Water Environmental Capacity Calculated Based on Point and Non-Point Source Pollution Emission Intensity under Water Quality Assurance Rates in a Tidal River Network Area.

A mathematical model for simulating hydrodynamics and pollutants migration in a tidal river network was constructed, which takes the temporal and spatial distribution of rainfall runoff and non-point pollutants into consideration. Under the design hydrologic conditions of a typical hydrological year, the daily concentration change process for the control section is obtained. Aiming at the uncertainty of hydrology and water quality parameters such as flow direction, flow rate and concentration change in tidal river network area, a statistical analysis method is used to obtain the maximum allowable concentration of pollutants in the control section under the condition of the water quality standard assurance rate of. Then, a formula for calculating the pollutions emission intensity of point and non-point sources is derived. The method was applied to the pollution source control in a typical region like Taihu in China.

STAYGREEN, STAY HEALTHY: a loss-of-susceptibility mutation in the STAYGREEN gene provides durable, broad-spectrum disease resistances for over 50 years of US cucumber production.

The Gy14 cucumber (Cucumis sativus) is resistant to oomyceteous downy mildew (DM), bacterial angular leaf spot (ALS) and fungal anthracnose (AR) pathogens, but the underlying molecular mechanisms are unknown. Quantitative trait locus (QTL) mapping for the disease resistances in Gy14 and further map-based cloning identified a candidate gene for the resistant loci, which was validated and functionally characterized by spatial-temporal gene expression profiling, allelic diversity and phylogenetic analysis, as well as local association studies. We showed that the triple-disease resistances in Gy14 were controlled by the cucumber STAYGREEN (CsSGR) gene. A single nucleotide polymorphism (SNP) in the coding region resulted in a nonsynonymous amino acid substitution in the CsSGR protein, and thus disease resistance. Genes in the chlorophyll degradation pathway showed differential expression between resistant and susceptible lines in response to pathogen inoculation. The causal SNP was significantly associated with disease resistances in natural and breeding populations. The resistance allele has undergone selection in cucumber breeding. The durable, broad-spectrum disease resistance is caused by a loss-of-susceptibility mutation of CsSGR. Probably, this is achieved through the inhibition of reactive oxygen species over-accumulation and phytotoxic catabolite over-buildup in the chlorophyll degradation pathway. The CsSGR-mediated host resistance represents a novel function of this highly conserved gene in plants.