Selective Removal of Hemicellulose by Diluted Sulfuric Acid Assisted by Aluminum Sulfate.

Hemicellulose can be selectively removed by acid pretreatment. In this study, selective removal of hemicellulose was achieved using dilute sulfuric acid assisted by aluminum sulfate pretreatment. The optimal pretreatment conditions were 160 °C, 1.5 wt% aluminum sulfate, 0.7 wt% dilute sulfuric acid, and 40 min. A component analysis showed that the removal rate of hemicellulose and lignin reached 98.05% and 9.01%, respectively, which indicated that hemicellulose was removed with high selectivity by dilute sulfuric acid assisted by aluminum sulfate pretreatment. Structural characterizations (SEM, FTIR, BET, TGA, and XRD) showed that pretreatment changed the roughness, crystallinity, pore size, and functional groups of corn straw, which was beneficial to improve the efficiency of enzymatic hydrolysis. This study provides a new approach for the high-selectivity separation of hemicellulose, thereby offering novel insights for its subsequent high-value utilization.

Alkali injury-induced pathological lymphangiogenesis in the iris facilitates the infiltration of T cells and ocular inflammation.

Inflammatory lymphangiogenesis is intimately linked to immune regulation and tissue homeostasis. However, current evidence has suggested that classic lymphatic vessels are physiologically absent in intraocular structures. Here, we show that neolymphatic vessels were induced in the iris after corneal alkali injury (CAI) in a VEGFR3-dependent manner. Cre-loxP-based lineage tracing revealed that these lymphatic endothelial cells (LECs) originate from existing Prox1+ lymphatic vessels. Notably, the ablation of iridial lymphangiogenesis via conditional deletion of VEGFR3 alleviated the ocular inflammatory response and pathological T cell infiltration. Our findings demonstrate that iridial neolymphatics actively participate in pathological immune responses following injury and suggest intraocular lymphangiogenesis as a valuable therapeutic target for the treatment of ocular inflammation.

The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300.

Acetylation of histones by lysine acetyltransferases (KATs) provides a fundamental mechanism by which chromatin structure and transcriptional programs are regulated. Here, we describe a dual binding activity of the first winged helix domain of human MORF KAT (MORFWH1) that recognizes the TAZ2 domain of p300 KAT (p300TAZ2) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300TAZ2 binding sites, allowing MORFWH1 to independently engage either ligand. Genomic data show that MORF/MOZWH1 colocalizes with H3K18ac, a product of enzymatic activity of p300, on CpG rich promoters of target genes. Our findings suggest a functional cooperation of MORF and p300 KATs in transcriptional regulation.

Macrophage-induced integrin signaling promotes Schlemm's canal formation to prevent intraocular hypertension and glaucomatous optic neuropathy.

Schlemm's canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvß3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced ß-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin ß3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvß3 signaling to improve SC functionality.

Enolase of Streptococcus suis serotype 2 promotes biomolecular condensation of ribosomal protein SA for HBMECs apoptosis.

BACKGROUND: Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear. RESULTS: Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis. CONCLUSIONS: Together, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces' RPSA.

Rational Design of Vinylene Carbonate-Inspired 1,3-Dimethyl-1H-imidazol-2(3H)-one Additives to Stabilize High-Voltage Lithium Metal Batteries.

Lithium metal batteries (LMBs) employing high-voltage nickel-rich cathodes represent a promising strategy to enable higher energy density storage systems. However, instability at the electrolyte-electrode interfaces (EEIs) currently impedes the translation of these advanced systems into practical applications. Herein, 1,3-dimethyl-1H-imidazol-2(3H)-one (DMIO), integrating structural features of vinylene carbonate (VC) while substituting oxygen with electron-donating nitrogen, has been synthesized and validated as a multifunctional electrolyte additive for high-voltage LMBs. Theoretical calculations and experimental results demonstrate that the potent electron-donating nitrogen in DMIO enables preferential DMIO oxidation at the cathode while preserving its carbon-carbon double bond for a concomitant reduction on the anode. Thereby, robust DMIO-derived EEIs are generated, reinforcing cycling in the full cells. Additionally, DMIO leverages Lewis acid-based interactions to coordinate and sequester protons from acidic LiPF6 decomposition byproducts, concurrently retarding LiPF6 hydrolysis while attenuating parasitic consumption of EEIs by acidic species. Consequently, incorporating DMIO into conventional carbonate electrolytes enables an improved capacity retention of Li||NCM622 cells to 81% versus 26% in the baseline electrolyte after 600 cycles. Similarly, DMIO improves Li anode cycling performance, displaying extended life spans over 200 h in Li||Li symmetric cells and enhancing Coulombic efficiency from 76% to 88% in Li||Cu cells. The synergistic effects of DMIO on both the cathode and anode lead to substantially improved cell lifetime. This rationally designed, multifunctional electrolyte additive paradigm provides vital insights that can be translatable to further electrolyte molecular engineering strategies.

A self-powered and self-sensing knee negative energy harvester.

Wearable devices realize health monitoring, information transmission, etc. In this study, the human-friendliness, adaptability, reliability, and economy (HARE) principle for designing human energy harvesters is first proposed and then a biomechanical energy harvester (BMEH) is proposed to recover the knee negative energy to generate electricity. The proposed BMEH is mounted on the waist of the human body and connected to the ankles by ropes for driving. Double-rotor mechanism and half-wave rectification mechanism design effectively improves energy conversion efficiency with higher power output density for more stable power output. The experimental results demonstrate that the double-rotor mechanism increases the output power of the BMEH by 70% compared to the single magnet-rotor mechanism. And the output power density of BMEH reaches 0.07 W/kg at a speed of 7 km/h. Furthermore, the BMEH demonstrates the excitation mode detection accuracy of 99.8% based on the Gate Recurrent Unit deep learning model with optimal parameters.

CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

Value of 18F-FDG PET/CT in breast cancer with second primary malignancies.

PURPOSE: To investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer (BC) with second primary malignancies (SPMs). MATERIALS AND METHODS: 149 BC patients (149/1419, 10.5 %) ultimately diagnosed with SPMs were included in the study. The following data were evaluated: age, location, the treatment of the first BC, the interval between the first BC and SPMs, the maximum diameter of SPMs, the maximum standardized uptake value (SUVmax) of SPMs, and SPMs metastases. The overall survival (OS) and progression-free survival (PFS) of follow-up patients were analyzed. The diagnostic efficiency of 18F-FDG PET/CT for SPMs and consistency with the pathological findings were calculated. RESULTS: The most common SPMs of BC was lung cancer (81/149, 54.4 %), particularly early-stage lung adenocarcinoma. There were the shorter maximum diameter of SPMs, the lower SUVmax of SPMs, and the fewer SPMs metastases in the lung cancer group than non-lung cancer group (P<0.001). The OS and PFS of the follow-up patients in the lung cancer group were longer than non-lung cancer group (P<0.001). The SPMs metastases was independent prognostic indicator of OS. The pathological grouping and the SPMs metastases were independent prognostic indicators of PFS. 18F-FDG PET/CT efficacy in diagnosing SPMs in BC patients was high. Compared with the pathological findings, the consistency was good (P = 0.010). CONCLUSION: Applying 18F-FDG PET/CT in BC patients might be helpful in detecting SPMs and partially predicting patient prognosis, in addition to its primary function in the diagnosis and staging of BC.

Stable anchoring of single rhodium atoms by indium in zeolite alkane dehydrogenation catalysts.

Maintaining the stability of single-atom catalysts in high-temperature reactions remains extremely challenging because of the migration of metal atoms under these conditions. We present a strategy for designing stable single-atom catalysts by harnessing a second metal to anchor the noble metal atom inside zeolite channels. A single-atom rhodium-indium cluster catalyst is formed inside zeolite silicalite-1 through in situ migration of indium during alkane dehydrogenation. This catalyst demonstrates exceptional stability against coke formation for 5500 hours in continuous pure propane dehydrogenation with 99% propylene selectivity and propane conversions close to the thermodynamic equilibrium value at 550°C. Our catalyst also operated stably at 600°C, offering propane conversions of >60% and propylene selectivity of >95%.

TENT5A Increases Glioma Malignancy and Promotes its Progression.

BACKGROUND: Recent studies reported that terminal nucleotidyltransferase 5A (TENT5A) is highly expressed in glioblastoma and associated with poor prognosis. In this work, we aim to specify the expression level of TENT5A in different grades of glioma and explore its role in glioma progression. METHODS: GEPIA online tools were used to perform the bioinformatic analysis. qRT-PCR, Western blot, and Immunohistochemistry were performed in glioma cells or tissues. Furthermore, CCK8, colony formation, transwell, flow cytometry and scratch assays were performed. RESULTS: TENT5A was highly expressed in glioma and its level was associated with the pathological grade of glioma. Knockdown of TENT5A suppressed cell proliferation, colony formation ability, cell invasion and migration. Overexpression of TENT5A was lethal to the glioma cells. CONCLUSION: Our data showed that the expression of TENT5A is associated with the pathological grade of glioma. Knockdown of TENT5A decreased the ability of proliferation, invasion and migration of glioma cells. High levels of TENT5A in glioma cells are lethal. Therefore, TENT5A could be a new target for glioma treatment.

Uracil hydrazones: design, synthesis, antimicrobial activities, and putative mode of action.

BACKGROUND: Crop diseases caused by plant pathogenic fungi and bacteria have led to substantial losses in global food production. Chemical pesticides have been widely used as a primary means to mitigate these issues. Nevertheless, the persistent and excessive use of pesticides has resulted in the emergence of microbial resistance. Moreover, the improper application and excessive utilization of pesticides can contribute to environmental pollution and the persistence of pesticide residues. Consequently, the development of novel and highly effective bactericides and fungicides to combat plant pathogens holds immense practical importance. RESULTS: A series of uracil hydrazones IV-B was deliberately designed and evaluated for their antimicrobial efficacy. The results of bioassays indicated that most IV-B exhibited >80% inhibition against the fungal species Monilia fructigena and Sclerotium rolfsii, as well as the bacterial species Clavibacter michiganensis subsp. michiganensis, Xanthomonas oryzae pv. oryzae, and Ralstonia solanacearum, at 50 µg/mL in vitro. In vivo, IV-B20 showed 89.9% of curative and 71.8% of protective activities against C. michiganensis subsp. michiganensis at 100 µg/mL superior to thiodiazole copper and copper hydroxide. IV-B20 also showed excellent protective activity against M. fructigena (96.3% at 200 µg/mL) and S. rolfsii (80.4% at 1000 µg/mL), which were greater than chlorothalonil and equivalent to thifluzamide. Mechanistic studies revealed that IV-B20 induced oxidative damage in pathogenic bacteria and promoted the leakage of cellular contents. CONCLUSION: This study suggests that IV-B20 with uracil hydrazone skeleton has great potential as an antimicrobial candidate. These findings lay a foundation for practical application in agriculture. © 2023 Society of Chemical Industry.

Green synthesis of silver nanoparticles using Phlebopus portentosus polysaccharide and their antioxidant, antidiabetic, anticancer, and antimicrobial activities.

Silver nanoparticles (AgNPs) by green synthesis from fungi polysaccharides are attracting increasing attention owing to their distinctive features and special applications in numerous fields. In this study, a cost-effective and environmentally friendly biosynthesizing AgNPs method with no toxic chemicals involved from the fruiting body polysaccharide of Phlebopus portentosus (PPP) was established and optimized by single factor experiment and response surface methodology. The optimum synthesis conditions of polysaccharide-AgNPs (PPP-AgNPs) were identified to be the reaction time of 140 min, reaction temperature of 94 °C, and the PPP: AgNO3 ratio of 1:11.5. Formation of PPP-AgNPs was indicated by visual detection of colour change from yellowish to yellowish brown. PPP-AgNPs were characterized by different methods and further evaluated for biological activities. That the Ultraviolet-visible (UV-Vis.) spectroscopy displayed a sharp absorption peak at 420 nm confirmed the formation of AgNPs. Fourier transform infrared (FTIR) analysis detected the presence of various functional groups. The lattice indices of (111), (200), (220), and (331), which indicated a faced-centered-cubic of the Ag crystal structure of PPP-AgNPs, was confirmed by X-ray diffraction (XRD) and the particles were found to be spherical through high resolution transmission electron microscopy (HRTEM). Energy dispersive X-ray spectroscopy (EDS) determined the presence of silver in PPP-AgNPs. The percentage relative composition of elements was determined as silver (Ag) 82.5 % and oxygen (O) 17.5 % for PPP-AgNPs, and did not exhibit any nitrogen peaks. The specific surface area of PPP-AgNPs was calculated to be 0.5750 m2/g with an average pore size of 24.33 nm by BET analysis. The zeta potential was -4.32 mV, which confirmed the stability and an average particle size of 64.5 nm was calculated through dynamic light scattering (DLS). PPP-AgNPs exhibited significant free radical scavenging activity against DPPH with an IC50 value of 0.1082 mg/mL. The MIC values of PPP-AgNPs for E. coli, S. aureus, C. albicans, C. glabrata, and C. parapsilosis are 0.05 mg/mL. The IC50 value of the inhibition of PPP-AgNPs against α-glucosidase was 11.1 µg/mL, while the IC50 values of PPP-AgNPs against HepG2 and MDA-MB-231 cell lines were calculated to be 14.36 ± 0.43 µg/mL and 40.05 ± 2.71 µg/mL, respectively. According to the evaluation, it can be concluded that these green-synthesized and eco-friendly PPP-AgNPs are helpful to improve therapeutics because of significant antioxidant, antimicrobial, antidiabetic, and anticancer properties to provide new possibilities for clinic applications.

Predicting stroke and myocardial infarction risk in Takayasu arteritis with automated machine learning models.

Few models exist for predicting severe ischemic complications (SIC) in patients with Takayasu arteritis (TA). We conducted a retrospective analysis of 703 patients with TA from January 2010 to December 2019 to establish an SIC prediction model for TA. SIC was defined as ischemic stroke and myocardial infarction. SIC was present in 97 of 703 (13.8%) patients with TA. Common iliac artery, coronary artery, internal carotid artery, subclavian artery, vertebral artery, renal artery involvement, chest pain, hyperlipidemia, absent pulse, higher BMI, vascular occlusion, asymmetric blood pressure in both upper limbs, visual disturbance, and older age were selected as predictive risk factors. Considering both discrimination and calibration performance, the Weighted Subspace Random Forest model was the most optimal model, boasting an area under the curve of 0.773 (95% confidence interval [0.652, 0.894]) in the validation cohort. Effective models for predicting SIC in TA may help clinicians identify high-risk patients and make targeted interventions.

The glycoprotein 5 of porcine reproductive and respiratory syndrome virus stimulates mitochondrial ROS to facilitate viral replication.

IMPORTANCE: Porcine reproductive and respiratory syndrome virus (PRRSV) presents a significant economic concern for the global swine industry due to its connection to serious production losses and increased mortality rates. There is currently no specific treatment for PRRSV. Previously, we had uncovered that PRRSV-activated lipophagy to facilitate viral replication. However, the precise mechanism that PRRSV used to trigger autophagy remained unclear. Here, we found that PRRSV GP5 enhanced mitochondrial Ca2+ uptake from ER by promoting ER-mitochondria contact, resulting in mROS release. Elevated mROS induced autophagy, which alleviated NLRP3 inflammasome activation for optimal viral replication. Our study shed light on a novel mechanism revealing how PRRSV exploits mROS to facilitate viral replication.

Burden of female infertility in China from 1990 to 2019: a temporal trend analysis and forecasting, and comparison with the global level.

BACKGROUND: Infertility is a common reproductive disease that affects not only individuals and families, but also the growth of the social population. Hence, understanding the burden of female infertility in China and worldwide is of great significance for the development of infertility prevention and treatment strategies. METHODS: The Global Burden of Disease Study (GBD 2019) Data Resources were used to collect and collate relevant data on female infertility in China and worldwide from 1990 to 2019. The difference in the number, age-standardised prevalence rate (ASPR), disability-adjusted life years and age-standardised disability-adjusted life years rate (ASDR) of women with infertility in different periods and geographical areas were analysed. The autoregressive integrated moving average method was used to predict the ASPR and ASDR of female infertility in China and worldwide in the next 11years. RESULTS: In the past 30years, the number of female infertility cases increased by 7.06million in China and 56.71million worldwide. The corresponding average annual increase of ASPR was 10.10% and 7.28%, respectively, and that of ASDR was 0.08% and 0.79%, respectively. In addition, there are differences in age and time between Chinese and global female infertility. In 1990, the crude prevalence rate of female infertility was the highest in women aged 40-44years and 35-39years in China and worldwide, respectively. In 2019, the crude prevalence rate of female infertility was still the highest in women aged 40-44years in China, whereas that around the world reached the highest in women aged 30-34years, which was significantly earlier. The forecast for the next 11years suggests that the ASPR and ASDR for female infertility in China will first rise and then decline, but the overall magnitude of change is not very significant, whereas the ASPR and ASDR for female infertility globally are still on the rise. The ASPR value of female infertility is expected to be 5025.56 in 100 000 persons in China and 3725.51 in 100 000 persons worldwide by 2030. The ASDR value of female infertility is expected to be 26.16 in 100 000 persons in China and 19.96 in 100 000 persons worldwide by 2030. CONCLUSION: The burden of female infertility is still increasing in China and worldwide. Therefore, it is of great significance to pay more attention to infertile women, and advocate a healthy lifestyle to reduce the burden of disease for infertile women.

RhoA suppresses pseudorabies virus replication in vitro.

The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.

Activation of AIM2 by hepatitis B virus results in antiviral immunity that suppresses hepatitis C virus during coinfection.

IMPORTANCE: Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.

Squamous cell carcinoma associated with endometriosis in the uterus and ovaries: A case report.

BACKGROUND: Endometriosis is a common benign gynecological disease that causes dysmenorrhea in women of childbearing age. Malignant tumors derived from endometriosis are rarely reported and are found in only 1% of all patients with endometriosis. Here, we report a well-differentiated squamous cell carcinoma (SCC) caused by squamous metaplasia of endometriosis that co-occurred in the uterus and ovaries. CASE SUMMARY: A 57-year-old postmenopausal woman had a 6-month history of irregular uterine bleeding. The uterus and adnexa were examined by computed tomography, and there were two solid cystic masses in the pelvis and right adnexa. Histological findings of surgical specimens showed well-differentiated SCC arising from squamous metaplasia of ectopic endometrial glands in the uterus and ovaries. The patient received chemotherapy after surgery and was followed up for 3 mo without metastasis. CONCLUSION: The continuity between ectopic endometrial glands and SCC supports that SCC originates from ectopic endometrial glands with metaplasia towards squamous epithelium.

Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a severe threat to the health of pigs globally. Host factors play a critical role in PRRSV replication. Using PRRSV as a model for genome-scale CRISPR knockout (KO) screening, we identified a host factor critical to PRRSV infection: sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Our findings show that SMPDL3B restricted PRRSV attachment, entry, replication, and secretion and that its depletion significantly inhibited PRRSV proliferation, indicating that SMPDL3B plays a positive role in PRRSV replication. Our data also show that SMPDL3B deficiency resulted in an accumulation of intracellular lipid droplets (LDs). The expression level of key genes (ACC, SCD-1, and FASN) involved in lipogenesis was increased, whereas the fundamental lipolysis gene, ATGL, was inhibited when SMPDL3B was knocked down. Overall, our findings suggest that SMPDL3B deficiency can effectively inhibit viral infection through the modulation of lipid metabolism.