Acetyl coenzyme A carboxylase modulates lipogenesis and sugar homeostasis in Blattella germanica.

Lipid and sugar homeostasis is critical for insect development and survival. In this study, we characterized an acetyl coenzyme A carboxylase gene in Blattella germanica (BgACC) that is involved in both lipogenesis and sugar homeostasis. We found that BgACC was dominantly expressed in the fat body and integument, and was significantly upregulated after molting. Knockdown of BgACC in 5th-instar nymphs did not affect their normal molting to the next nymphal stage, but it caused a lethal phenotype during adult emergence. BgACC-RNA interference (RNAi) significantly downregulated total free fatty acid (FFA) and triacylglycerol (TAG) levels, and also caused a significant decrease of cuticular hydrocarbons (CHCs). Repression of BgACC in adult females affected the development of oocytes and resulted in sterile females, but BgACC-RNAi did not affect the reproductive ability of males. Interestingly, knockdown of BgACC also changed the expression of insulin-like peptide genes (BgILPs), which mimicked a physiological state of high sugar uptake. In addition, BgACC was upregulated when B. germanica were fed on a high sucrose diet, and repression of BgACC upregulated the expression of the glycogen synthase gene (BgGlyS). Moreover, BgACC-RNAi increased the circulating sugar levels and glycogen storage, and a longevity assay suggested that BgACC was important for the survival of B. germanica under conditions of high sucrose uptake. Our results confirm that BgACC is involved in multiple lipid biogenesis and sugar homeostasis processes, which further modulates insect reproduction and sugar tolerance. This study benefits our understanding of the crosstalk between lipid and sugar metabolism.

Novel fluorine-containing energetic materials: how potential are they? A computational study of detonation performance.

CONTEXT: High-energy density materials (HEDMs) have emerged as a research focus due to their advantageous ultra-high detonation performance and better sensitivity. The primary aim of this study revolves around crafting HEDMs that strike a delicate balance between exceptional performance and minimal sensitivity. Density functional theory (DFT) was utilized to evaluate the geometric structures, energies, densities, energy properties, and sensitivities of 39 designed derivatives. The theoretical density (ρ) and heat of formation (HOF) were used to estimate the detonation velocity (D) and pressure (P) of the title compounds. Our study shows that the introduction of fluorine-containing substituents or fluorine-free substituents into the CHOFN backbone or the CHON backbone can significantly enhance the detonation performance of derivatives. Derivative B1 exhibits the better overall performance, including superior density, detonation performance, and sensitivity (P = 58.89 GPa, D = 8.02 km/s, ρ = 1.93 g/cm3, and characteristic height H50 = 34.6 cm). Our molecular design strategy contributes to the development of more novel HEDMs with excellent detonation performance and stability. It also marks a significant step towards a material engineering era guided by theory-based rational design. METHODS: GaussView 6.0 was used for construction of molecular system coordinates, and Gaussian 16 was used to obtain optimal structures, energies, and volumes of all compounds at the B3LYP/6-31+G(d,p) level of theory. It was characterized to be the local energy minimum on the potential energy surface without imaginary frequencies at the same theory level. Molecular weight, isosurface area, and overall variance were obtained using the Multiwfn 3.3. The detonation properties of the materials were analyzed using the C-J thermodynamic detonation theory. Our broad analysis facilitated an extensive assessment of these properties.

Effectiveness of mHealth management with an implantable glucose sensor and a mobile application among Chinese adults with type 2 diabetes.

INTRODUCTION: This study aimed to evaluate the effectiveness of mHealth management with an implantable glucose sensor and a mobile application among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: A randomised controlled trial was carried out to compare the effectiveness of usual health management to mHealth management based on a model that consisted of the network platform, an implantable glucose sensor and a mobile app featuring guidance from general practitioners (GPs) over a four-week period. Patients (N=68) with T2DM were randomly divided into an intervention group and a control group. Before the intervention, there was no difference in body mass index (BMI), fasting blood glucose (FBG), postprandial two-hour blood glucose (2hPG) and glycosylated haemoglobin (HbA1c) between the intervention group and the control group (p>0.05). Patients in the control group received their usual health management, while patients in the intervention group received mHealth management. RESULTS: After health management, the mean BMI, FBG, 2hPG and HbA1c of the intervention group patients were all lower than those of the control group patients (p < 0.05), and the quality of life and self-management of the intervention group patients had significantly improved. DISCUSSION: mHealth management effectively showed significant reductions in BMI, FBG, 2hPG and HbA1c and improved quality of life and self-management among patients, which may be related to real-time feedback from an implantable glucose sensor and guidance from GPs through a mobile app. mHealth management is a very promising way to promote the health management of T2DM in China, and this study provides a point of reference for mHealth management abroad.

Effects of Dietary Nonfibrous Carbohydrate/Neutral Detergent Fiber Ratio on Methanogenic Archaea and Cellulose-Degrading Bacteria in the Rumen of Karakul Sheep: a 16S rRNA Gene Sequencing Study.

The study was conducted to investigate the effects of dietary nonfibrous carbohydrate (NFC)/neutral detergent fiber (NDF) ratio on methanogenic archaea and cellulose-degrading bacteria in Karakul sheep by 16S rRNA gene sequencing. Twelve Karakul sheep were randomly divided into four groups, each group with three replicates, and they were fed with four dietary NFC/NDF ratios at 0.54, 0.96, 1.37, and 1.90 as groups 1, 2, 3, and 4, respectively. The experiment lasted for four periods: I (1 to 18 days), II (19 to 36 days), III (37 to 54 days), and IV (55 to 72 days); during each period, rumen contents were collected before morning feeding to investigate on methanogenic archaea and cellulose-degrading bacteria. The results showed that with an increase in dietary NFC/NDF ratio, the number of rumen archaea operational taxonomic units and the diversity of archaea decrease. The most dominant methanogens did not change with dietary NFC/NDF ratio and prolongation of experimental periods. Methanobrevibacter was the most dominant genus. At the species level, the relative abundance of Methanobrevibacter ruminantium first increased and then decreased when the NFC/NDF ratio increased. When the dietary NFC/NDF ratio was 0.96, the structure of archaea was largely changed, and the relative abundance of Fibrobacter sp. strain UWCM, Ruminococcus flavefaciens, and Ruminococcus albus were the highest. When the dietary NFC/NDF ratio was 1.37, the relative abundance of Butyrivibrio fibrisolvens was higher than for other groups. Based on all the data, we concluded that a dietary NFC/NDF ratio of ca. 0.96 to 1.37 was a suitable ratio to support optimal sheep production. IMPORTANCE CH4 produced by ruminants aggravates the greenhouse effect and cause wastage of feed energy, and CH4 emissions are related to methanogens. According to the current literature, there is a symbiotic relationship between methanogens and cellulolytic bacteria, so reducing methane will inevitably affect the degradation of fiber materials. This experiment used 16S rRNA gene high-throughput sequencing technology to explore the balance relationship between methanogens and cellulolytic bacteria for the first time through a long-term feeding period. The findings provide fundamental data, supporting for the diet structures with potential to reduce CH4 emission.

New paeonol derivative C302 reduces hypertension in spontaneously hypertensive rats through endothelium-dependent and endothelium-independent vasodilation.

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K+ channels to restrain Ca2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development.

Melanin synthesis genes BgTH and BgDdc affect body color and cuticle permeability in Blattella germanica.

Melanin is involved in cuticle pigmentation and sclerotization of insects, which is critical for maintaining structural integrity and functional completeness of insect cuticle. The 2 key enzymes of tyrosine hydroxylase (TH) and dopa decarboxylase (DDC) predicted in melanin biosynthesis are usually conserved in insects. However, it is unclear whether their function is related to epidermal permeability. In this study, we identified and cloned the gene sequences of BgTH and BgDdc from Blattella germanica, and revealed that they both showed a high expression at the molting, and BgTH was abundant in the head and integument while BgDdc was expressed highest in the fat body. Using RNA interference (RNAi), we found that knockdown of BgTH caused molting obstacles in some cockroaches, with the survivors showing pale color and softer integuments, while knockdown of BgDdc was viable and generated an abnormal light brown body color. Desiccation assay showed that the dsBgTH-injected adults died earlier than control groups under a dry atmosphere, but dsBgDdc-injected cockroaches did not. In contrast, when dsRNA-treated cockroaches were reared under a high humidity condition, almost no cockroaches died in all treatments. Furthermore, with eosin Y staining assay, we found that BgTH-RNAi resulted in a higher cuticular permeability, and BgDdc-RNAi also caused slight dye penetration. These results demonstrate that BgTH and BgDdc function in body pigmentation and affect the waterproofing ability of the cuticle, and the reduction of cuticular permeability may be achieved through cuticle melanization.

Two putative fatty acid synthetic genes of BgFas3 and BgElo1 are responsible for respiratory waterproofing in Blattella germanica.

Water retention is critical for physiological homeostasis and survival in terrestrial insects. While deposition of hydrocarbons on insect cuticles as a key measure for water conservation has been extensively investigated, we know little about other mechanisms for preventing water loss in insects. Here, we report two fatty acid synthetic genes that are independent of hydrocarbon production but crucial for water retention in the German cockroach Blattella germanica (L.). First, an integument enriched fatty acid elongase gene (BgElo1) was identified as a critical gene for desiccation resistance in B. germanica; however, knockdown of BgElo1 surprisingly failed to cause a decline in cuticular lipids. In addition, RNA interference (RNAi)-knockdown of an upstream fatty acid synthase gene (BgFas3) showed a similar phenotype, and transmission electron microscopy analysis revealed that BgFas3- or BgElo1-RNAi did not affect cuticle architecture. Bodyweight loss test showed that repression of BgFas3 and BgElo1 significantly increased the weight loss rate, but the difference disappeared when the respiration was closed by freeze killing the cockroaches. A water immersion test was performed, and we found that BgFas3- and BgElo1-RNAi made it difficult for cockroaches to recover from drowning, which was supported by the upregulation of hypoxia-related genes after a 10-h recovery from drowning. Moreover, a dyeing assay with water-soluble Eosin Y showed that this was caused by the entry of water into the respiratory system. Our research suggests that BgFas3 and BgElo1 are required for both inward and outward waterproofing of the respiratory system. This study benefits the understanding of water retention mechanisms in insects.

Downregulation of NADPH-cytochrome P450 reductase via RNA interference increases the susceptibility of Acyrthosiphon pisum to desiccation and insecticides.

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is involved in the metabolism of endogenous and exogenous substances, and detoxification of insecticides. RNA interference (RNAi) of CPR in certain insects causes developmental defects and enhanced susceptibility to insecticides. However, the CPR of Acyrthosiphon pisum has not been characterized, and its function is still not understood. In this study, we investigated the biochemical functions of A. pisum CPR (ApCPR). ApCPR was found to be transcribed in all developmental stages and was abundant in the embryo stage, and in the gut, head, and abdominal cuticle. After optimizing the dose and silencing duration of RNAi for downregulating ApCPR, we found that ApCPR suppression resulted in a significant decrease in the production of cuticular and internal hydrocarbon contents, and of cuticular waxy coatings. Deficiency in cuticular hydrocarbons (CHCs) decreased the survival rate of A. pisum under desiccation stress and increased its susceptibility to contact insecticides. Moreover, desiccation stress induced a significant increase in ApCPR mRNA levels. We further confirmed that ApCPR participates in CHC production. These results indicate that ApCPR modulates CHC production, desiccation tolerance, and insecticide susceptibility in A. pisum, and presents a novel target for pest control.

Progress of thrombus formation and research on the structure-activity relationship for antithrombotic drugs.

Many populations suffer from thrombotic disorders such as stroke, myocardial infarction, unstable angina and thromboembolic disease. Thrombus is one of the major threatening factors to human health and the prevalence of cardio-cerebrovascular diseases induced by thrombus is growing worldwide, even some persons got rare and severe blood clots after receiving the AstraZeneca COVID vaccine unexpectedly. In terms of mechanism of thrombosis, antithrombotic drugs have been divided into three categories including anticoagulants, platelet inhibitors and fibrinolytics. Nowadays, a large number of new compounds possessing antithrombotic activities are emerging in an effort to remove the inevitable drawbacks of previously approved drugs such as the high risk of bleeding, a slow onset of action and a narrow therapeutic window. In this review, we describe the causes and mechanisms of thrombus formation firstly, and then summarize these reported active compounds as potential antithrombotic candidates based on their respective mechanism, hoping to promote the development of more effective bioactive molecules for treating thrombotic disorders.

Modulation of fatty acid elongation in cockroaches sustains sexually dimorphic hydrocarbons and female attractiveness.

Insect cuticular hydrocarbons (CHCs) serve as important intersexual signaling chemicals and generally show variation between the sexes, but little is known about the generation of sexually dimorphic hydrocarbons (SDHCs) in insects. In this study, we report the molecular mechanism and biological significance that underlie the generation of SDHC in the German cockroach Blattella germanica. Sexually mature females possess more C29 CHCs, especially the contact sex pheromone precursor 3,11-DimeC29. RNA interference (RNAi) screen against the fatty acid elongase family members combined with heterologous expression of the genes in yeast revealed that both BgElo12 and BgElo24 were involved in hydrocarbon (HC) production, but BgElo24 is of wide catalytic activities and is able to provide substrates for BgElo12, and only the female-enriched BgElo12 is responsible for sustaining female-specific HC profile. Repressing BgElo12 masculinized the female CHC profile, decreased contact sex pheromone level, and consequently reduced the sexual attractiveness of female cockroaches. Moreover, the asymmetric expression of BgElo12 between the sexes is modulated by sex differentiation cascade. Specifically, male-specific BgDsx represses the transcription of BgElo12 in males, while BgTra is able to remove this effect in females. Our study reveals a novel molecular mechanism responsible for the formation of SDHCs and also provide evidences on shaping of the SDHCs by sexual selection, as females use them to generate high levels of contact sex pheromone.

Lipophorin receptor regulates the cuticular hydrocarbon accumulation and adult fecundity of the pea aphid Acyrthosiphon pisum.

Cuticular hydrocarbons form a barrier that protects terrestrial insects from water loss via the epicuticle. Lipophorin loads and transports lipids, including hydrocarbons, from one tissue to another. In some insects, the lipophorin receptor (LpR), which binds to lipophorin and accepts its lipid cargo, is essential for female fecundity because it mediates the incorporation of lipophorin by developing oocytes. However, it is unclear whether LpR is involved in the accumulation of cuticular hydrocarbons and its precise role in aphid reproduction remains unknown. We herein present the results of our molecular characterization, phylogenetic analysis, and functional annotation of the pea aphid (Acyrthosiphon pisum) LpR gene (ApLpR). This gene was transcribed throughout the A. pisum life cycle, but especially during the embryonic stage and in the abdominal cuticle. Furthermore, we optimized the RHA interference (RNAi) parameters by determining the ideal dose and duration for gene silencing in the pea aphid. We observed that the RNAi-based ApLpR suppression significantly decreased the internal and cuticular hydrocarbon contents as well as adult fecundity. Additionally, a deficiency in cuticular hydrocarbons increased the susceptibility of aphids to desiccation stress, with decreased survival rates under simulated drought conditions. Moreover, ApLpR expression levels significantly increased in response to the desiccation treatment. These results confirm that ApLpR is involved in transporting hydrocarbons and protecting aphids from desiccation stress. Furthermore, this gene is vital for aphid reproduction. Therefore, the ApLpR gene of A. pisum may be a novel RNAi target relevant for insect pest management.

A water-soluble and incubate-free fluorescent environment-sensitive probe for ultrafast visualization of protein thiols within living cells.

The amount of protein thiols play a crucial role in maintaining the cellular redox homeostasis and have significant implications to indicate a series of diseases. Therefore, it is necessary to develop an ideal probe for protein thiol detection in a simple and readily implementable method. Consequently, a water-soluble and incubate-free fluorescent environment-sensitive probe DMTs-OCC was synthesized using 7-diethylamincoumarin as the fluorophore and 4-(5-Methanesulfonyl- [1,2,3,4]tetrazol-1-yl)-phenol (MSTP) as a thiol receptor reagent. The blue-shift emission spectra of probe DMTs-OCC was observed by ultrafast binding to protein sulfhydryl groups from the excited intramolecular charge transfer (ICT) to the twisted intramolecular charge transfer (TICT) conversion process in aqueous solution. The experimental results showed that probe DMTs-OCC exhibited an excellent selectivity to protein thiols and biocompatibility in aqueous solution, as well as terrific cell membrane permeability which enabled the successful visualization of BSA protein thiol in living cells. Moreover, no excess probe was cleaned and no incubation time was needed in cell experiments. Therefore, it could provide a new method to the construction of fluorescent probes for protein thiols labelling and visualization.

Biodegradable poly(lactic acid) nanocomposites reinforced and toughened by carbon nanotubes/clay hybrids.

Polylactic acid (PLA) is a biodegradable and biocompatible polyester derived from renewable resources like corn starch, presenting great potential in clinical applications like tissue engineering, implants and drug delivery systems. However, the intrinsic brittleness restricts its real applications. In this work, PLA nanocomposites were prepared by incorporating a small amount of carboxyl functionalized multi-walled carbon nanotubes (CNTs) and surface compatabilized montmorillonite (MMT) via technologies of freeze-drying and masterbatch-based melt blending. In the resulting nanocomposites, a well-distributed nano-filler network with microstructures of 1-D CNTs/2-D MMT platelets is formed favored by the enhanced interfacial interaction between the organic modified fillers with PLA matrix. Thanks to the well dispersed organic modified nanofillers, a large number of microcracks and extremely stretched PLA matrix are induced during tensile process, dissipating amounts of energy. As a result, the filler networks reinforce PLA with increment of 19% in modulus, remarkably increase by 13.8 times in toughness relative to PLA control without sacrificing strength. Thus, the PLA nanocomposites with excellent properties prepared through the facile and effective route possess broad prospect in biomedical applications.

Selective dispersion of carbon nanotubes and nanoclay in biodegradable poly(ε-caprolactone)/poly(lactic acid) blends with improved toughness, strength and thermal stability.

Poly(ε-caprolactone)/poly(lactic acid) (PCL/PLA) blends are promising biomaterials with biodegradable characteristics. However, poor compatibility of the two components may lead to undesirable mechanical properties. In this work, the effect of combining carboxyl multi-walled carbon nanotubes (CNTs) and organically modified montmorillonite (MMT) on the morphology and properties of PCL/PLA blend was investigated. The morphological observations and rheological analysis showed that exfoliated MMT platelets enhanced interfacial adhesion of the two phases, whereas CNTs formed a percolating network in PCL matrix. The addition of CNTs/MMT (0.5 wt%: 0.5 wt%) led to an increase by 137.4% in elongation at break, 79.6% in tensile strength, and 14 °C in decomposition temperature without sacrificing its rigidity apparently for the PCL/PLA matrix. Obvious synergistic effect was demonstrated in comparison to the blends containing single nanofiller. This study demonstrated that combining CNTs and MMT is a facile way to preparing immiscible PCL/PLA blends based nanocomposites with interesting structure and properties.

Establishment of the Permeability Model for Soft Solid Sludge Conditioned with Flocculants.

Permeability plays a decisive role in the dewatering process and reflects the difficulty of filtration, especially for soft solid material such as sludge. In this paper, the physicochemical properties and dewatering performance of sludge conditioned with different kinds of flocculants were investigated. Results showed that the flocculant could change the sludge microstructure such as floc morphology, specific surface area, and fractal dimension. Compared with filtration pressure, flocculants had a greater influence on sludge permeability which was a significant negative correlation with filtration pressure and was a positive correlation with flocculant dosage. In order to describe the fact that fluid flows through the porous voids for soft solid sludge, the improved Kozeny constant was corrected. Research showed that permeability was more significant in the dewatering process for the sludge conditioned with inorganic flocculants than that with organic flocculants. The Kozeny constant was not only relevant with suspension nature but also with filtration pressure. The range of the improved Kozeny constant was reasonably determined based on flocculant type, concentration, and filtration pressure, which was of great help to project applications. For raw sludge, the improved Kozeny constant was 958 times than that of the original value, and it decreased significantly for conditioned sludge.

Semi-solid rheology characterization of sludge conditioned with inorganic coagulants.

Rheology measurement, a state-of-the-art technology in a multitude of engineering disciplines, has often been used for computational fluid dynamic simulation of wastewater treatment processes, especially in anaerobic digestion and dewatering. In this work, rheological tests were used to study the semi-solid characteristics of sludge and a good result was obtained. The inorganic coagulants polyaluminum chloride (PAC) and ferric chloride (FC) both increased the floc strength of sludge, leading to higher rheology parameters such as elastic modulus, viscous modulus and specific thixotropy area. Curiously, the shape of all rheological curves exhibited little change with increasing coagulant dosage. The results indicated that various physical and chemical actions among coagulants and sludge flocs relate only to rigid structure, not to the nature of rheology behavior. Frequency sweep tests clearly showed that elastic modulus was a logarithmic function of frequency, suggesting that sludge could not properly be called a soft material due to its inorganic particles. An improved viscoelastic model was successfully developed to predict the experimental data of creep and recovery tests in the linear viscoelastic region. Furthermore, complicated viscoelastic behavior of sludge was also observed, and all the rheology tests could provide the optimum dosage of PAC but not the optimum dosage of FC.

Rheology characteristics of activated sludge and thermal treated sludge at different process temperature.

In this paper, flow behavior for activated sludge and thermal treated sludge at different process temperature and various solids content were analyzed. Results show viscosity of activated sludge and thermal treated sludge both decreased with increasing temperature, while temperature dependence of viscosity for both types of sludge were not same at the whole study range. The relationship between viscosity and temperature could be expressed by Arrhenius equation for activated sludge, and it was interesting that this law was only suitable when certain solid content (80 g/L) for thermal treated sludge. Moreover, the logistic model was certified to be accurate in describing the functionality for thermal treated sludge. As solid content was at range of 80-100 g/L, active energy of viscosity for both kinds of sludge were similar, indicating that physicochemical properties' change of sludge after thermal hydrolysis had little effect on viscosity sensibility. Arrhenius law was also suitable for describing the relationship between storage modulus and process temperature for activated sludge. However, for thermal treated sludge, Arrhenius law was invalid. Yield stress for activated sludge was prominent, while it could be ignored for thermal treated sludge.

[TG-fTIR study of the thermal-conversion properties of holo-cellulose derived from woody biomass].

Thermal-conversion properties of cellulose, hemi-cellulose and holo-cellulose derived from woody biomass were studied using TG-FTIR, and also compared to those of avicel cellulose and xylan. 3-D diffusion model was applied to calculate the kinetic parameters of thermal-conversion reaction of biomass materials, such as the activation energy, pre-exponential factors, etc, which showed good regression results. With the analysis of three-dimensional IR spectra of gas products, featured peaks of HzO, CO, CO2, CH4, and oxygenates were obviously observed where showing up with the maximum weight-loss rate in DTG curves. The possible forming routes of major gaseous products were analyzed and discussed. The order of releasing amounts for gaseous productions was approximately as CO2 > H2O > CO CH4. Based on the comprehensive understanding and comparative analysis of the whole results, it is concluded that the thermal conversion process of holo-cellulose was the result of interaction between cellulose and hemi-cellulose under the dominant role of cellulose.