RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila.

Histone modification and nucleosome assembly play important roles in chromatin-related processes. Histone chaperones form different complexes and coordinate histone transportation and assembly. Various histone chaperone complexes have been identified in different organisms. The ciliate protozoa (ciliates) have various chromatin structures and different nuclear morphology. However, histone chaperone components and functions of different subunits remain unclear in ciliates. Tetrahymema thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally inactive micronucleus (MIC) which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental stages. Here, we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental stages. REBL1 knockdown inhibited cellular proliferation. The macronuclear morphology became bigger in growing mutants. The abnormal macronuclear structure also occurred in the starvation stage. Furthermore, micronuclear meiosis was disturbed during sexual development, leading to a failure to generate new gametic nuclei. RebL1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental stages. REBL1 knockdown affected expression levels of the genes involved in chromatin organization and transcription. Taken together, RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in T. thermophila. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00219-z.

Delaying age at first sexual intercourse provides protection against oral cavity cancer: a mendelian randomization study.

Aim: To investigate whether age at first sexual intercourse could lead to any changes in the risk of oral cavity cancer. Methods: A two-sample mendelian randomization was conducted using genetic variants associated with age at first sexual intercourse in UK biobank as instrumental variables. Summary data of Northern American from a previous genome-wide association study aimed at oral cavity cancer was served as outcome. Three analytical methods: inverse variance-weighted, mendelian randomization Egger, and weighted median were used to perform the analysis, among which inverse variance-weighted was set as the primary method. Robustness of the results was assessed through Cochran Q test, mendelian randomization Egger intercept tests, MR PRESSO, leave one out analysis and funnel plot. Results: The primary analysis provided substantial evidence of a positive causal relationship age at first sexual intercourse and the risk of oral cavity cancer (p = 0.0002), while a delayed age at first sexual intercourse would lead to a decreased risk of suffering oral cavity cancer (ß = -1.013). The secondary outcomes confirmed the results (all ß < 0) and all assessments supported the robustness, too (all p > 0.05). Conclusion: The study demonstrates that a delayed sexual debut would provide protection against OCC, thus education on delaying sexual intercourse should be recommended.

Active site-tuned high peroxidase-like activity nanozyme for on-the-spot detection of saliva total antioxidant capacity using smartphone devices.

Metal-Organic Framework (MOF) based nanozymes with clear structure are beneficial for exploration of structural-performance and exhibit broad prospects in improving activity. In this study, the prepared bimetallic Fe3Ni-MOF nanozyme was superior to single metal MOF in the peroxidase-like activity. Subsequently, a derivative nanozyme (Fe3Ni-MOF-Ar) was prepared by pyrolysis using Fe3Ni-MOF as the precursor in argon atomoshere with controlled temperature. The investigated of Fe3Ni-MOF-Ar revealed that the irregular macroporous state and the presence of heterovalent FeIII/FeII sites of Fe3Ni-MOF-Ar enable the retention, exposure, and electronic structure regulation of active sites, promoting the dual mechanism (the generation of •OH and electron transfer mechanism) and significantly increasing the peroxidase-like activity. Fe3Ni-MOF-Ar exhibited a strong affinity for substrate H2O2, which is higher than horseradish peroxidase. Ascorbic acid and cysteine are typical substances of antioxidants. Fe3Ni-MOF-Ar was used for sensitive colorimetric detection of ascorbic acid and cysteine, and the detection limit was as low as 150 and 60 nM. In addition, the smartphone devices was used to detection of antioxidant equivalent ascorbic acid, with a detection range of 0.5-120 µM. Fe3Ni-MOF-Ar nanozyme is feasible for sensitive detection of saliva total antioxidant capacity.

Aberrant auditory metabolite levels and topological properties are associated with cognitive decline in presbycusis patients.

Presbycusis has been reported as related to cognitive decline, but its underlying neurophysiological mechanism is still unclear. This study aimed to investigate the relationship between metabolite levels, cognitive function, and node characteristics in presbycusis based on graph theory methods. Eighty-four elderly individuals with presbycusis and 63 age-matched normal hearing controls underwent magnetic resonance spectroscopy, functional magnetic resonance imaging scans, audiological assessment, and cognitive assessment. Compared with the normal hearing group, presbycusis patients exhibited reduced gamma-aminobutyric acid and glutamate levels in the auditory region, increased nodal characteristics in the temporal lobe and precuneus, as well as decreased nodal characteristics in the superior occipital gyrus and medial orbital. The right gamma-aminobutyric acid levels were negatively correlated with the degree centrality in the right precuneus and the executive function. Degree centrality in the right precuneus exhibited significant correlations with information processing speed and executive function, while degree centrality in the left medial orbital demonstrated a negative association with speech recognition ability. The degree centrality and node efficiency in the superior occipital gyrus exhibited a negative association with hearing loss and speech recognition ability, respectively. These observed changes indicate alterations in metabolite levels and reorganization patterns at the brain network level after auditory deprivation.

ß-Cyclodextrin metal-organic framework as a green carrier to improve the dissolution, bioavailability, and liver protective effect of luteolin.

The incidence of acetaminophen-induced liver injury has increased, but effective prevention methods are limited. Although luteolin has hepatoprotective activity, its low solubility and bioavailability limit its applications. Cyclodextrin metal-organic frameworks (CD-MOFs) possess 3D-network structures and large inner cavities, which make them excellent carriers of poorly soluble drugs. In this study, we used CD-MOFs as carriers to improve the dissolution of luteolin and assessed their antioxidant activity, bioavailability, and hepatoprotective effects. Luteolin was loaded into ß-CD-MOF, γ-CD-MOF, ß-CD, and γ-CD, and characterized by powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TGA). Our results showed that luteolin-ß-CD-MOF was the most stable. The main driving forces were hydrogen bonds and van der Waals forces, as determined by molecular simulation. The loading capacity of luteolin-ß-CD-MOF was 14.67 wt%. Compared to raw luteolin, luteolin-ß-CD-MOF exhibited a 4.50-fold increase in dissolution and increased antioxidant activity in vitro. Luteolin-ß-CD-MOF increased the bioavailability of luteolin by approximately 4.04- and 11.07-fold in healthy rats and liver injured rats induced by acetaminophen in vivo, respectively. As determined by biochemical analysis, luteolin-ß-CD-MOF exhibited a better hepatoprotective effect than raw luteolin in rats with acetaminophen-induced liver injury. This study provides a new approach for preventing acetaminophen-mediated liver damage.

Gastrodin regulates the expression of renin-angiotensin system-SIRT3 and proinflammatory mediators in reactive astrocytes via activated microglia.

Gastrodin, an anti-inflammatory herbal agent, is known to suppress microglia activation. Here, we investigated whether it would exert a similar effect in reactive astrocytes and whether it might act through the renin-angiotensin system (RAS) and sirtuin 3 (SIRT3). Angiotensinogen (ATO), angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) and type 2 (AT2) receptor and SIRT3 expression was detected in TNC-1 astrocytes treated with BV-2 microglia conditioned medium (CM) with or without gastrodin and lipopolysaccharide (LPS) pre-treatment by RT-PCR, immunofluorescence and western blotting analysis. Expression of C3 (A1 astrocyte marker), S100A10 (A2 astrocyte marker), proinflammatory cytokines and neurotrophic factors was then evaluated. The results showed a significant increase of ATO, ACE, AT1, SIRT3, C3, proinflammatory cytokines and neurotrophic factors expression in TNC-1 astrocytes incubated in CM + LPS when compared with cells incubated in the CM, but AT2 and S100A10 expression was reduced. TNC-1 astrocytes responded vigorously to BV-2 CM treated with gastrodin + LPS as compared with the control. This was evident by the decreased expression of the abovementioned protein markers, except for AT2 and S100A10. Interestingly, SIRT3, IGF-1 and BDNF expression was enhanced, suggesting that gastrodin inhibited the expression of RAS and proinflammatory mediators but promoted the expression of neurotrophic factors. And gastrodin regulated the phenotypic changes of astrocytes through AT1. Additionally, azilsartan (a specific inhibitor of AT1) inhibited the expression of C3 and S100A10, which remained unaffected in gastrodin and azilsartan combination treatment. These findings provide evidence that gastrodin may have a therapeutic effect via regulating RAS-SIRT3.

Interlukin-22 improves ovarian function in polycystic ovary syndrome independent of metabolic regulation: a mouse-based experimental study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology. METHODS: The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (Fshrcre+Stat3f/f) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from Fshrcre+Stat3f/f mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function. RESULTS: We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from Fshrcre+Stat3f/f did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function. CONCLUSION: IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.

Serum metabolomics analyses reveal biomarkers of osteoporosis and the mechanism of Quanduzhong capsules.

With the aging of the population, the prevalence of osteoporosis (OP) is rising rapidly, making it an important public health concern. Early screening and effective treatment of OP are the primary challenges facing the management of OP today. Quanduzhong capsule (QDZ) is a single preparation composed of Eucommia ulmoides Oliv., which is included in the Pharmacopoeia of the People's Republic of China. It is used to treat OP in clinical practice, but its mechanisms are unclear. This study involved 30 patients with OP, 30 healthy controls (HC), and 28 OP patients treated with QDZ to identify potential biomarkers for the early diagnosis of OP and to investigate the potential mechanism of QDZ in treating OP. The serum samples were analyzed using targeted amino acid metabolomics. Significant differences in amino acid metabolism were identified between the OP cohort and the HC group, as well as between OP patients before and after QDZ treatment. Compared with HC, the serum levels of 14 amino acids in OP patients changed significantly. Kynurenine, arginine, citrulline, methionine, and their combinations are expected to be potential biomarkers for OP diagnosis. Notably, QDZ reversed the changes in levels of 10 amino acids in the serum of OP patients and significantly impacted numerous metabolic pathways during the treatment of OP. This study focuses on screening potential biomarkers for the early detection of OP, which offers a new insight into the mechanism study of QDZ in treating OP.

Evidence from China's shipping sector on the impact of fiscal measures in enabling a low-carbon economic transition.

The Green Economy Initiative aims to achieve economic development while minimizing carbon emissions by implementing a low-carbon economy across all sectors. It is noteworthy that ships play a significant role in global commodity transportation, accounting for approximately 80-90 percent. However, this also leads to a surge in fossil fuel consumption and alarming pollution levels. The data utilized in this article spans from 2010 to 2022 and specifically focuses on the shipping industry, drawing from information collected in 20 different provinces of China. Multiple panel regression models were constructed to analyze the influence of fiscal policies on facilitating the transition toward a low-carbon economy. In addition, a vector autoregression model was employed to examine the interconnected dynamics between low-carbon transition and budgetary guidelines. The findings indicate that tax-based policies demonstrate an inverted U-shaped relationship with low-carbon transition, whereas transfer payment policies exhibit an N-shaped pattern. The shipping sector is actively embracing low-carbon practices, largely due to incorporating digital technologies that mitigate the adverse impacts of fiscal regulations.

Sea anemone-anemonefish symbiosis: Behavior and mucous protein profiling.

Fish species of the genus Amphiprion (Perciformes: Pomacentridae) seek protection from predators among the tentacles of sea anemones as their natural habitat, where they live essentially unharmed from stinging by the host's nematocysts. The skin mucus of these anemonefish has been suggested as a protective mechanism that prevents the discharge of the nematocysts upon contact. Whereas some anemonefish species seem to produce their own protective mucous coating, others may acquire mucus (or biomolecules within) from the sea anemone during an acclimation period. In controlled experiments, we show that Amphiprion ocellaris acclimated successfully to their natural host anemone species Stichodactyla gigantea, and also to Stichodactyla haddoni, and in some cases Heteractis crispa, neither of which are natural host species. No symbiosis was observed for three other anemone species tested, Entacmaea quadricolor, Macrodactyla doreensis, and Heteractis malu. We explored the skin mucous protein profile from naive and experienced A. ocellaris during their acclimation to natural and unnatural host anemones. We confidently report the presence of metabolic and structural proteins in the skin mucus of all samples, likely involved in immunological defense, molecular transport, stress response, and signal transduction. For those anemonefish that established symbiosis, there was a clear increase in ribosomal-type proteins. We additionally provide evidence for the presence of anemone proteins only in the skin mucus of individuals that established symbiosis. Our results support previous speculation of the role of skin mucous-associated proteins in anemonefish-anemone symbiosis. Further exploration of these mucosal proteins could reveal the mechanism of anemonefish acclimation to host anemones.

New Opportunities for Electric Fields in Promoting Wound Healing: Collective Electrotaxis.

SIGNIFICANCE: It has long been hypothesized that naturally occurring electric fields (EFs) aid wound healing by guiding cell migration. Consequently, the application of EFs has significant potential for promoting wound healing. However, the mechanisms underlying the cellular response to EFs remain unclear. Recent Advances： Although the directed migration of isolated single cells under EFs has been studied for decades, only recently has experimental evidence demonstrated the distinct collective migration of large sheets of keratinocytes and corneal epithelial cells in response to applied EFs. Accumulating evidence suggests that the emergent properties of cell groups in response to EF guidance offer new opportunities for EF-assisted directional migration. CRITICAL ISSUES: In this review, we provide an overview of the field of collective electrotaxis, highlighting key advances made in recent years. We also discuss advanced engineering strategies utilized to manipulate collective electrotaxis. FUTURE DIRECTIONS: We outline a series of unanswered questions in this field and propose potential applications of collective electrotaxis in developing electrical stimulation technologies for wound healing.

Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution.

Background: The role of human lineage mutations (HLMs) in human evolution through post-transcriptional modification is unclear. Aims: To investigate the contribution of HLMs to human evolution through post-transcriptional modification. Methods: We applied a deep learning model Seqweaver to predict how HLMs impact RNA-binding protein affinity. Results: We found that only 0.27% of HLMs had significant impacts on RNA-binding proteins at the threshold of the top 1% of human common variations. These HLMs enriched in a set of conserved genes highly expressed in adult excitatory neurons and prenatal Purkinje neurons, and were involved in synapse organisation and the GTPase pathway. These genes also carried excess damaging coding mutations that caused neurodevelopmental disorders, ataxia and schizophrenia. Among these genes, NTRK2 and ITPR1 had the most aggregated evidence of functional importance, suggesting their essential roles in cognition and bipedalism. Conclusions: Our findings suggest that a small subset of human-specific mutations have contributed to human speciation through impacts on post-transcriptional modification of critical brain-related genes.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries.

AIMS: The clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). METHODS: We analyzed data from 34,224 youths (51.0 % boys, aged 6-18 years) with CMRFs, 5004 (49.5 % boys, aged 6-18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6-17 years) with PWV measurement from 20 pediatric samples across 14 countries. RESULTS: WHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75-0.78) to 0.78 (0.76-0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74-0.79) to 0.77 (0.74-0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64-0.71) to 0.70 (0.66-0.73) for high cIMT (≥P95 values) and from 0.60 (0.58-0.66) to 0.62 (0.58-0.66) for high PWV (≥P95 values). CONCLUSIONS: Our findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

A near-infrared fluorescent probe for simultaneous detection of pH and viscosity.

In this work, we developed a ratiometric fluorescent probe (NT) based on ICT framework in near-infrared (NIR) which could detect pH and viscosity simultaneously. Long emission wavelength in NIR could protect the probe from interference of background fluorescence and improve the accuracy of the test. Due to the presence of thiazole-salt, the probe possessed good water solubility and could respond immediately to pH in water system. The pH values measured by NT in the actual samples were not much different from that measured by the pH meter, therefore, NT could give excellent accuracy. NT realized the reversible detection of pH by protonation and deprotonation. NT was used successfully to detect the pH of actual water samples, human serum and meat, as well as the viscosity variation caused by thickeners. Additionally, NT could monitor the changes of pH and viscosity in living cells. Therefore, the novel probe exhibited potential application in the fields of the environment, human health and food safety evaluation.

A pro-reparative bioelectronic device for controlled delivery of ions and biomolecules.

Wound healing is a complex physiological process that requires precise control and modulation of many parameters. Therapeutic ion and biomolecule delivery has the capability to regulate the wound healing process beneficially. However, achieving controlled delivery through a compact device with the ability to deliver multiple therapeutic species can be a challenge. Bioelectronic devices have emerged as a promising approach for therapeutic delivery. Here, we present a pro-reparative bioelectronic device designed to deliver ions and biomolecules for wound healing applications. The device incorporates ion pumps for the targeted delivery of H+ and zolmitriptan to the wound site. In vivo studies using a mouse model further validated the device's potential for modulating the wound environment via H+ delivery that decreased M1/M2 macrophage ratios. Overall, this bioelectronic ion pump demonstrates potential for accelerating wound healing via targeted and controlled delivery of therapeutic agents to wounds. Continued optimization and development of this device could not only lead to significant advancements in tissue repair and wound healing strategies but also reveal new physiological information about the dynamic wound environment.

206,977 newborn screening results reveal the ethnic differences in the spectrum of inborn errors of metabolism in Huaihua, China.

Background: Inborn errors of metabolism (IEMs) are rare diseases caused by inherited defects in various biochemical pathways that strongly correlate with early neonatal mortality and stunting. Currently, no studies have reported on the incidence of IEMs of multi-ethnic groups in Huaihua, China. Methods: A total of 206,977 neonates with self-reported ethnicity who underwent IEM screening at Huaihua from 2015 to 2021 were selected for observation. Among them, 69 suspected IEM-positive neonates were referred for urine gas chromatography-mass spectrometry analysis, biochemical detection, next-generation sequencing, and Sanger sequencing. Results: Sixty-nine newborns were diagnosed with IEMs, with an overall incidence of 1:3,000. The two most common disorders were 2-methylbutyryl glycinuria (1:7,137) and phenylalanine hydroxylase deficiency (1:22,997). Moreover, the incidence of IEMs in the minority ethnic group (Miao, Dong, Tujia and Yao) (1:1,852) was markedly higher than in the Han ethnic group (1:4,741). Some ethnic features variants were identified; NM_001609.4:c.1165A>G in the ACADSB gene for Miao and Dong ethnic groups, NM_014251.2:c.852_855del in the SLC25A13 gene for Miao ethnic groups. Conclusion: This study revealed the IEM incidence within the minority ethnic groups is markedly higher than among the Han nationality and the gene variant spectrum is dramatically different in Huaihua, China. Hence, It serves as a theoretical reference for the screening and diagnosing of neonatal IEMs of multi-ethnic groups in the Huaihua area, and across China.

Underwater light source changes microecosystem constructed by Vallisneria spinulosa Yan for water restoration: Efficiency of water purification, characteristics of growth, and rhizosphere.

Submerged macrophytes are effective in ecological restoration of water bodies polluted by nitrogen and phosphorus, and its restoration capacity depends on underwater illumination condition. This study explored the influencing mechanism of illumination on Vallisneria spinulosa Yan (V. spinulosa Yan) for water restoration. Addition of underwater light source increased the total nitrogen, ammonia nitrogen, total phosphorus, and phosphate removal loads of the V. spinulosa Yan growth system by 61.5, 39.2, 8.5, and 5.0 mg m-2 d-1, respectively. Meanwhile, the growth of V. spinulosa Yan was obviously promoted, even with high water turbidity. Although the biological nitrogen removal processes were inhibited by adding underwater light source, the growth of V. spinulosa Yan can be significantly improved, thus enhancing the efficiency of water purification via the absorption of nitrogen and phosphorus by V. spinulosa Yan. This study provides a theoretical foundation and technical support for application of submerged macrophytes in ecological water restoration.

Characteristics of lipid metabolism after treatment of colon cancer mice with American ginseng vesicles.

INTRODUCTION: Lipid molecules are present in tumours and play an important role in the anti-inflammatory response as well as in antiviral protection. Changes in the type and location of lipids in the intestine following exposure to environmental stressors play an important role in several disorders, including ulcerative colitis (UC), inflammatory bowel disease (IBD), and colorectal cancer. OBJECTIVES: The aim of this work is to provide a new theoretical basis for tumour initiation and development by accurately measuring the spatial distribution of lipids and metabolites in intestinal tissue. Spatial metabolomics allows the detection of samples with minimal sample volume by label-free imaging of complex samples in their original state. The distribution of lipid molecules in tumours has not been reported, although the distribution of lipid molecules in intestinal tissue has been reported in the literature. METHODS: The range of lipid profiles in colon cancer mouse tumour tissue was compiled using a spatial metabolomics: lipid extraction method. The changes in lipid distribution in two regions after oral administration of American Ginseng (Panax quinquefolius L.) vesicles were also compared. Tumour tissue samples were extracted with 80% methanol-20% formic acid in water. RESULTS: The resulting spatial metabolic profile allowed the identification of seven lipid classes in mouse tumours. The distribution of fibre tissue cells was 23.2% higher than tumour tissue cells, with the exception of the fatty acid (FA) species.