TIP aquaporins in Cyperus esculentus: genome-wide identification, expression profiles, subcellular localizations, and interaction patterns.

BACKGROUND: Tonoplast intrinsic proteins (TIPs), which typically mediate water transport across vacuolar membranes, play an essential role in plant growth, development, and stress responses. However, their characterization in tigernut (Cyperus esculentus L.), an oil-bearing tuber plant of the Cyperaceae family, is still in the infancy. RESULTS: In this study, a first genome-wide characterization of the TIP subfamily was conducted in tigernut, resulting in ten members representing five previously defined phylogenetic groups, i.e., TIP1-5. Although the gene amounts are equal to that present in two model plants Arabidopsis and rice, the group composition and/or evolution pattern were shown to be different. Except for CeTIP1;3 that has no counterpart in both Arabidopsis and rice, complex orthologous relationships of 1:1, 1:2, 1:3, 2:1, and 2:2 were observed. Expansion of the CeTIP subfamily was contributed by whole-genome duplication (WGD), transposed, and dispersed duplications. In contrast to the recent WGD-derivation of CeTIP3;1/-3;2, synteny analyses indicated that TIP4 and - 5 are old WGD repeats of TIP2, appearing sometime before monocot-eudicot divergence. Expression analysis revealed that CeTIP genes exhibit diverse expression profiles and are subjected to developmental and diurnal fluctuation regulation. Moreover, when transiently overexpressed in tobacco leaves, CeTIP1;1 was shown to locate in the vacuolar membrane and function in homo/heteromultimer, whereas CeTIP2;1 is located in the cell membrane and only function in heteromultimer. Interestingly, CeTIP1;1 could mediate the tonoplast-localization of CeTIP2;1 via protein interaction, implying complex regulatory patterns. CONCLUSIONS: Our findings provide a global view of CeTIP genes, which provide valuable information for further functional analysis and genetic improvement through manipulating key members in tigernut.

Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC.

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.

The relationship between clustering and networked Turing patterns.

Networked Turing patterns often manifest as groups of nodes distributed on either side of the homogeneous equilibrium, exhibiting high and low density. These pattern formations are significantly influenced by network topological characteristics, such as the average degree. However, the impact of clustering on them remains inadequately understood. Here, we investigate the relationship between clustering and networked Turing patterns using classical prey-predator models. Our findings reveal that when nodes of high and low density are completely distributed on both sides of the homogeneous equilibrium, there is a linear decay in Turing patterns as global clustering coefficients increase, given a fixed node size and average degree; otherwise, this linear decay may not always hold due to the presence of high-density nodes considered as low-density nodes. This discovery provides a qualitative assessment of how clustering coefficients impact the formation of Turing patterns and may contribute to understanding why using refuges in ecosystems could enhance the stability of prey-predator systems. The results link network topological structures with the stability of prey-predator systems, offering new insights into predicting and controlling pattern formations in real-world systems from a network perspective.

Molecular characterization of oleosin genes in Cyperus esculentus, a Cyperaceae plant producing oil in underground tubers.

KEY MESSAGE: CeOLE genes exhibit a tuber-predominant expression pattern and their mRNA/protein abundances are positively correlated with oil accumulation during tuber development. Overexpression could significantly increase the oil content of tobacco leaves. Oleosins (OLEs) are abundant structural proteins of lipid droplets (LDs) that function in LD formation and stabilization in seeds of oil crops. However, little information is available on their roles in vegetative tissues. In this study, we present the first genome-wide characterization of the oleosin family in tigernut (Cyperus esculentus L., Cyperaceae), a rare example accumulating high amounts of oil in underground tubers. Six members identified represent three previously defined clades (i.e. U, SL and SH) or six out of seven orthogroups (i.e. U, SL1, SL2, and SH1-3) proposed in this study. Comparative genomics analysis reveals that lineage-specific expansion of Clades SL and SH was contributed by whole-genome duplication and dispersed duplication, respectively. Moreover, presence of SL2 and SH3 in Juncus effuses implies their appearance sometime before Cyperaceae-Juncaceae divergence, whereas SH2 appears to be Cyperaceae specific. Expression analysis showed that CeOLE genes exhibit a tuber-predominant expression pattern and transcript levels are considerably more abundant than homologs in the close relative Cyperus rotundus. Moreover, CeOLE mRNA and protein abundances were shown to positively correlate with oil accumulation during tuber development. Additionally, two dominant isoforms (i.e. CeOLE2 and -5) were shown to locate in LDs as well as the endoplasmic reticulum of tobacco (Nicotiana benthamiana) leaves, and are more likely to function in homo and heteromultimers. Furthermore, overexpression of CeOLE2 and -5 in tobacco leaves could significantly increase the oil content, supporting their roles in oil accumulation. These findings provide insights into lineage-specific family evolution and putative roles of CeOLE genes in oil accumulation of vegetative tissues, which facilitate further genetic improvement for tigernut.

A time independent least squares algorithm for parameter identification of Turing patterns in reaction-diffusion systems.

Turing patterns arising from reaction-diffusion systems such as epidemic, ecology or chemical reaction models are an important dynamic property. Parameter identification of Turing patterns in spatial continuous and networked reaction-diffusion systems is an interesting and challenging inverse problem. The existing algorithms require huge account operations and resources. These drawbacks are amplified when apply them to reaction-diffusion systems on large-scale complex networks. To overcome these shortcomings, we present a new least squares algorithm which is rooted in the fact that Turing patterns are the stationary solutions of reaction-diffusion systems. The new algorithm is time independent, it translates the parameter identification problem into a low dimensional optimization problem even a low order linear algebra equations. The numerical simulations demonstrate that our algorithm has good effectiveness, robustness as well as performance.

Optimal control of pattern formations for an SIR reaction-diffusion epidemic model.

Patterns arising from the reaction-diffusion epidemic model provide insightful aspects into the transmission of infectious diseases. For a classic SIR reaction-diffusion epidemic model, we review its Turing pattern formations with different transmission rates. A quantitative indicator, "normal serious prevalent area (NSPA)", is introduced to characterize the relationship between patterns and the extent of the epidemic. The extent of epidemic is positively correlated to NSPA. To effectively reduce NSPA of patterns under the large transmission rates, taken removed (recovery or isolation) rate as a control parameter, we consider the mathematical formulation and numerical solution of an optimal control problem for the SIR reaction-diffusion model. Numerical experiments demonstrate the effectiveness of our method in terms of control effect, control precision and control cost.

The qualitative and quantitative relationships between pattern formation and average degree in networked reaction-diffusion systems.

The Turing pattern is an important dynamic behavior characteristic of activator-inhibitor systems. Differentiating from traditional assumption of activator-inhibitor interactions in a spatially continuous domain, a Turing pattern in networked reaction-diffusion systems has received much attention during the past few decades. In spite of its great progress, it still fails to evaluate the precise influences of network topology on pattern formation. To this end, we try to promote the research on this important and interesting issue from the point of view of average degree-a critical topological feature of networks. We first qualitatively analyze the influence of average degree on pattern formation. Then, a quantitative relationship between pattern formation and average degree, the exponential decay of pattern formation, is proposed via nonlinear regression. The finding holds true for several activator-inhibitor systems including biology model, ecology model, and chemistry model. The significance of this study lies that the exponential decay not only quantitatively depicts the influence of average degree on pattern formation, but also provides the possibility for predicting and controlling pattern formation.

Optimal control of the reaction-diffusion process on directed networks.

Reaction-diffusion processes organized in networks have attracted much interest in recent years due to their applications across a wide range of disciplines. As one type of most studied solutions of reaction-diffusion systems, patterns broadly exist and are observed from nature to human society. So far, the theory of pattern formation has made significant advances, among which a novel class of instability, presented as wave patterns, has been found in directed networks. Such wave patterns have been proved fruitful but significantly affected by the underlying network topology, and even small topological perturbations can destroy the patterns. Therefore, methods that can eliminate the influence of network topology changes on wave patterns are needed but remain uncharted. Here, we propose an optimal control framework to steer the system generating target wave patterns regardless of the topological disturbances. Taking the Brusselator model, a widely investigated reaction-diffusion model, as an example, numerical experiments demonstrate our framework's effectiveness and robustness. Moreover, our framework is generally applicable, with minor adjustments, to other systems that differential equations can depict.

[Hepatic Insulin Resistance and Type 2 Diabetes Mellitus].

Insulin resistance (IR) is a pathological reaction of hyperinsulinemia and impaired glucose tolerance caused by decreased sensitivity of target tissues such as liver to insulin.The pathogenesis of IR as a typical pathological feature of type 2 diabetes is the focus of anti-diabetes research.In this paper,we reviewed the molecular mechanisms of glucose and lipid metabolism,oxidative stress,mitochondrial dysfunction,endoplasmic reticulum stress,inflammation,and hepatic IR in the case of type 2 diabetes mellitus,which might provide new ideas and theoretical guidance for the treatment of diabetes mellitus.

Superhydrophobic and Antioxidative Film Based on Edible Materials for Food Packaging.

Significant wastage of the food deterioration in the food preserving process and residual liquid in a container has become a major concern for scientists and the whole society. In this study, an edible multifunctional film integrated superhydrophobicity and antioxidant ability is constructed by chitosan, tea polyphenol, carnauba wax material that is food and drug administration (FDA)-approved for food packaging. The formed edible packaging materials that exhibit great antioxidant property and extremely low water-absorbing quality, was thus proven to display excellent fresh beef preservation effect during storage of 14 days. Importantly, the formed edible multifunctional interface was also demonstrated to perform excellent superhydrophobicity due to the carnauba wax and exhibited large contact angles for various liquid foods, which could effectively reduce the liquid residue. Moreover, the formed edible multifunctional packaging materials showed good thermostability and biocompatibility, which has the potential to be applied as a functional packaging material.

Changes of Gastric Juice Microenvironment in Patients with Fundic Gland Polyp and Hyperplastic Polyp.

INTRODUCTION: The aim of this study was to study the relationship between the formation of gastric fundic gland polyp and gastric hyperplastic polyp (HP) and the changes of gastric juice microenvironment. METHODS: The proton-pump inhibitor (PPI) applications to patients were recorded. Gastric juices and biopsy polyps were collected for pathological examination, H. pylori tests, biomarkers, and MUC1, MUC2, MUC5AC expression measurement. RESULTS: Among 34,892 patients, the detection rate of gastric fundic gland polyps was significantly higher than that of gastric HPs (p < 0.01). The incidence rate of gastric fundic gland polyp and gastric HP in PPI users (n = 3,886) was higher than that of non-PPI users (p < 0.01). The occurrence of polyp was positively related to the duration of PPI application and the H. pylori-positive rate. The bile reflux rate between fundic gland polys group (17.61%) and HPs (28.67%) was significantly different (p < 0.01). The levels of gastric juice Gastrin-17, epidermal growth factor (EGF) and MUC2 from patients with gastric fundic gland polyps and gastric HPs were higher than those in the control group (p < 0.01). However, patients with gastric fundic gland polyps and HPs had significantly lower gastric juice PGE2 and MUC5AC (p < 0.01). CONCLUSION: PPI application, H. pylori infection, and bile reflux are the potential risk factors for formation of fundic gland polyps and HPs. The potential mechanism of polyps' formation can be related to the levels of Gastrin-17, EGF, MUC2, PGE2, and MUC5AC in gastric juice.

Comparison of the effect of post-exercise cooling with ice slurry ingestion between males and females.

This study aimed to compare the effects of ice slurry ingestion on post-exercise cooling in males and females. Twenty-four healthy adults (male n = 12; body weight [BW], 65.8 ± 10.3 kg; female, n = 12; BW, 58.2 ± 10.0 kg) participated in this study. Participants ingested 7.5 g/kg of either ice slurry at -1 °C (ICE) or control fluid at 20 °C (CON) during recovery after cycling at 55% VO2max until the rectal temperature reached 38.5 °C or exhaustion in a hot environment (controlled at 38 °C, 40% relative humidity). Rectal (Tre) and skin (Tsk) temperature, ratings of thermal sensation (TS), thermal comfort (TC), heart rate (HR), mean arterial pressure (MAP), and whole body sweat loss (WBSL) were measured 60 min after exercise. Ice slurry ingestion reduced Tre and TS and improved post-exercise hypotension only in females (p < 0.05). In comparison, males did not receive cooling effect from post- exercise cooling with ice slurry ingestion. WBSL tended to be lower in ICE than CON in males (ICE, 454.3 ± 172.3 g; CON, 539.7 ± 157.2 g; p = 0.065). In conclusion, sex differences were observed in the effects of post-exercise cooling with ice slurry ingestion.

Genome-wide analysis and phosphorylation sites identification of the 14-3-3 gene family and functional characterization of MeGRF3 in cassava.

The biological functionality of many members of the 14-3-3 gene family is regulated via phosphorylation at multiple amino acid residues. The specific phosphorylation-mediated regulation of these proteins during cassava root tuberization, however, is not well understood. In this study, 15 different 14-3-3 genes (designated MeGRF1 - 15) were identified within the cassava genome. Based upon evolutionary conservation and structural analyses, these cassava 14-3-3 proteins were grouped into ε and non-ε clusters. We found these 15 MeGRF genes to be unevenly distributed across the eight cassava chromosomes. When comparing the expression of these genes during different developmental stages, we found that three of these genes (MeGRF9, 12 and 15) were overexpressed at all developmental stages at 75, 104, 135, 182 and 267 days post-planting relative to the fibrous root stage, whereas two (MeGRF5 and 7) were downregulated during these same points. In addition, the expression of most MeGRF genes changed significantly in the early and middle stages of root tuberization. This suggests that these different MeGRF genes likely play distinct regulatory roles during cassava root tuberization. Subsequently, 18 phosphorylated amino acid residues were detected on nine of these MeGRF proteins. A phosphomimetic mutation at serine-65 in MeGRF3 in Arabidopsis thaliana (Arabidopsis) slightly influenced starch metabolism in these plants, and significantly affected the role of MeGRF3 in salt stress responses. Together these results indicate that 14-3-3 genes play key roles in responses to abiotic stress and the regulation of starch metabolism, offering valuable insights into the functions of these genes in cassava.

Cross-diffusion-induced patterns in an SIR epidemic model on complex networks.

Infectious diseases are a major threat to global health. Spatial patterns revealed by epidemic models governed by reaction-diffusion systems can serve as a potential trend indicator of disease spread; thus, they have received wide attention. To characterize important features of disease spread, there are two important factors that cannot be ignored in the reaction-diffusion systems. One is that a susceptible individual has an ability to recognize the infected ones and keep away from them. The other is that populations are usually organized as networks instead of being continuously distributed in space. Consequently, it is essential to study patterns generated by epidemic models with self- and cross-diffusion on complex networks. Here, with the help of a linear analysis method, we study Turing instability induced by cross-diffusion for a network organized SIR epidemic model and explore Turing patterns on several different networks. Furthermore, the influences of cross-diffusion and network structure on patterns are also investigated.

Differences between sexes in thermoregulatory responses and exercise time during endurance exercise in a hot environment following pre-cooling with ice slurry ingestion.

This study aimed to examine differences between sexes in thermoregulatory responses and exercise time after ice slurry ingestion in a hot environment. Twenty-four healthy adults (male n = 12, body weight (BW) = 65.8 ± 10.3; female n = 12, BW = 58.2 ± 10.0) ingested 7.5 g/kg of either ice slurry at -1 °C (ICE) or control water at 20 °C (CON) before cycling at 55%VO2 max in a hot environment (controlled at 38 °C, 40% relative humidity). Rectal (Tre) and skin (Tsk) temperature, heart rate, sweat rate, respiratory gases, ratings of thermal sensation (TS), thermal comfort (TC), and rating of perceived exertion (RPE) were measured. Ice slurry did not improve exercise time in both sexes despite Tre was significantly lower in ICE than CON in both sexes. Tre, Tsk, HR, sweat rate and TS did not differ between sexes. TC and RPE in ICE were significantly higher during exercise in males than in females. In conclusion, there were no sex differences in the effects of pre-cooling with ice slurry ingestion; however, pre-cooling with ice slurry may be more effective in mitigating ratings of TC and RPE in females than males.

An improved protein extraction method applied to cotton leaves is compatible with 2-DE and LC-MS.

BACKGROUND: Two-dimensional electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are widely used in plant proteomics research. However, these two techniques cannot be simultaneously satisfied by traditional protein extraction methods when investigate cotton leaf proteome. RESULTS: Here, we evaluated the efficiency of three different protein extraction methods for 2-DE and LC-MS/MS analyses of total proteins obtained from cotton leaves. The protein yield of the borax/PVPP/phenol (BPP) method (0.14%) was significantly lower than the yields of the trichloroacetic acid/acetone (TCA) precipitation method (1.42%) and optimized TCA combined with BPP (TCA-B) method (0.47%). The BPP method was failed to get a clear 2-DE electrophoretogram. Fifty pairs of protein spots were randomly selected from the 2-DE gels of TCA- and TCA-B-extracted proteins for identification by MALDI TOF/TOF, and the results of 42 pairs were consistent. High-throughput proteomic analysis showed that 6339, 9282 and 9697 unique proteins were identified from the total cotton leaf proteins extracted by the TCA, BPP and TCA-B methods, respectively. Gene Ontology (GO) analysis revealed that the proteins specifically identified by TCA method were primarily distributed in the plasma membrane, while BPP and TCA-B methods specific proteins distributed in the cytosol, indicating the sub-cellular preference of different protein extraction methods. Further, ATP-dependent zinc metalloprotease FTSH 8 could be observed in the 2-DE gels of TCA and TCA-B methods, and could only be detected in the LC-MS/MS results of the BPP and TCA-B methods, showing that TCA-B method might be the optimized choice for both 2-DE and LC-MS/MS. CONCLUSION: Our data provided an improved TCA-B method for protein extraction that is compatible with 2-DE and LC-MS/MS for cotton leaves and similar plant tissues which is rich in polysaccharides and polyphenols.

miRNA-126 enhances viability, colony formation, and migration of keratinocytes HaCaT cells by regulating PI3 K/AKT signaling pathway.

Wound healing is a basic biological process including proliferation and migration of keratinocyte. The effects of microRNAs on skin wound healing remain largely unexplored. This study aimed to investigate the role of microRNA-126 (miR-126) in human skin wound healing. Relative expression of miR-126 after injury was evaluated by qRT-PCR. Cell viability, colony formation, cycle distribution, migration, and the alternation of PI3 K/AKT pathway after miR-126 knockdown or overexpression were detected, respectively. In addition, potential target gene of miR-126 was also explored by luciferase assay. Results showed that miR-126 was up-regulated during skin wound healing. Moreover, overexpression of miR-126 promoted cell proliferation and migration, whereas inhibition of miR-126 led to the opposite effects. Additionally, we discovered that PLK2, which inhibited cell viability, colony formation and migration of keratinocyte, was a target gene of miR-126. The expression of PLK2 was negatively correlated with the level of miR-126 during wound healing. Finally, we demonstrated that overexpression of miR-126 significantly increased the expression of p-AKT, p-ERK2, and PI3 K, indicating that overexpression of miR-126 activated PI3 K/AKT signaling pathway. In conclusion, our results demonstrated that miR-126 acted as a critical regulator for promoting proliferation and migration in keratinocyte during skin wound healing.

Proteomic Landscape Has Revealed Small Rubber Particles Are Crucial Rubber Biosynthetic Machines for Ethylene-Stimulation in Natural Rubber Production.

Rubber particles are a specific organelle for natural rubber biosynthesis (NRB) and storage. Ethylene can significantly improve rubber latex production by increasing the generation of small rubber particles (SRPs), regulating protein accumulation, and activating many enzyme activities. We conducted a quantitative proteomics study of different SRPs upon ethylene stimulation by differential in-gel electrophoresis (DIGE) and using isobaric tags for relative and absolute quantification (iTRAQ) methods. In DIGE, 79 differentially accumulated proteins (DAPs) were determined as ethylene responsive proteins. Our results show that the abundance of many NRB-related proteins has been sharply induced upon ethylene stimulation. Among them, 23 proteins were identified as rubber elongation factor (REF) and small rubber particle protein (SRPP) family members, including 16 REF and 7 SRPP isoforms. Then, 138 unique phosphorylated peptides, containing 129 phosphorylated amino acids from the 64 REF/SRPP family members, were identified, and most serine and threonine were phosphorylated. Furthermore, we identified 226 DAPs from more than 2000 SRP proteins by iTRAQ. Integrative analysis revealed that almost all NRB-related proteins can be detected in SRPs, and many proteins are positively responsive to ethylene stimulation. These results indicate that ethylene may stimulate latex production by regulating the accumulation of some key proteins. The phosphorylation modification of REF and SRPP isoforms might be crucial for NRB, and SRP may act as a complex natural rubber biosynthetic machine.

Comparison and analysis of statins drug use in the treatment of diastolic dysfunction in patients.

Statins have multiple anti lipid effects, such as anti-inflammatory, anti-oxidation and anti arteriosclerosis, which are beneficial to improve cardiac function. Statins can effectively improve left ventricular remodeling and protect ventricular diastolic function. In this study, the effects of statin therapy on diastolic function and BNP level and exercise tolerance after exercise were observed by statins in patients with diastolic dysfunction. The results showed that after atorvastatin treatment, the exercise BNP decreased in the treatment group, which was significantly different from that before treatment and in the control group (P<0.05). This study demonstrated that atorvastatin was used to treat patients with diastolic dysfunction and exercise hypertension by lowering blood pressure and reducing exercise SBP, anti-inflammatory and improving vascular endothelial function.

A protein extraction method for low protein concentration solutions compatible with the proteomic analysis of rubber particles.

The extraction of high-purity proteins from the washing solution (WS) of rubber particles (also termed latex-producing organelles) from laticifer cells in rubber tree for proteomic analysis is challenging due to the low concentration of proteins in the WS. Recent studies have revealed that proteins in the WS might play crucial roles in natural rubber biosynthesis. To further examine the involvement of these proteins in natural rubber biosynthesis, we designed an efficiency method to extract high-purity WS proteins. We improved our current borax and phenol-based method by adding reextraction steps with phenol (REP) to improve the yield from low protein concentration samples. With this new method, we extracted WS proteins that were suitable for proteomics. Indeed, compared to the original borax and phenol-based method, the REP method improved both the quality and quantity of isolated proteins. By repeatedly extracting from low protein concentration solutions using the same small amount of phenol, the REP method yielded enough protein of sufficiently high-quality from starting samples containing less than 0.02 mg of proteins per milliliter. This method was successfully applied to extract the rubber particle proteins from the WS of natural rubber latex samples. The REP-extracted WS proteins were resolved by 2DE, and 28 proteins were positively identified by MS. This method has the potential to become widely used for the extraction of proteins from low protein concentration solutions for proteomic analysis.