Pseudostellaria heterophylla polysaccharide mitigates Alzheimer's-like pathology via regulating the microbiota-gut-brain axis in 5 × FAD mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuroinflammation, for which gut dysbiosis may be implicated. Our previous study showed that treatment with Pseudostellaria heterophylla aqueous extract and one of its cyclopeptides, heterophyllin B, attenuate memory deficits via immunomodulation and neurite regeneration. However, whether Pseudostellaria heterophylla polysaccharide (PH-PS) exerts neuroprotective effects against AD and its underlying mechanisms remain unclear. The infrared spectrum, molecular weight, and carbohydrate composition of the PH-PS were determined. The results showed that PH-PS (Mw 8.771 kDa) was composed of glucose (57.78 %), galactose (41.52 %), and arabinose (0.70 %). PH-PS treatment ameliorated learning and spatial memory deficits, reduced amyloid ß build-up, and suppressed reactive glia and astrocytes in 5 × FAD mice. 16S rRNA sequencing further showed that PH-PS remodelled the intestinal flora composition by promoting probiotic microbiota, such as Lactobacillus, Muribaculum, Monoglobus, and [Eubacterium]_siraeum_group, and suppressing inflammation-related UCG-009 and Blautia. Additionally, PH-PS restored intestinal barrier function; ameliorated peripheral inflammation by reducing the secretion of inflammatory cytokines, thereby converting M1 microglia and A1 astrocyte toward beneficial M2 and A2 phenotypes; and contributed to Aß plaques clearance by upregulation of insulin degradation enzyme and neprilysin. Collectively, our findings demonstrate that PH-PS may prevent the progression of AD via modulation of the gut microbiota and regulation of glial polarisation, which could provide evidence to design a potential diet therapy for preventing or curing AD.

Evaluation of Clinical Efficacy of Acupuncture and Moxibustion for Asthma: Systematic Review and Meta-Analysis.

Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).

Carboxymethyl cellulose and carboxymethyl chitosan-based composite nanogel as a stable delivery vehicle for oyster peptides: Characterization, absorption and transport mechanism.

An oyster peptide (OPs)-loaded composite nanogel based on carboxymethyl cellulose and carboxymethyl chitosan (CMC@CMCS@OPs) was prepared, and the characterization, absorption and transport mechanism were further investigated. CMC@CMCS@OPs, a dense spherical microstructure with a diameter of ∼64 nm, which enhanced the thermal and digestive stabilities of individual OPs and improved its retention rate of hypoglycemic activity in vitro. The swelling response and in-vitro release profiles showed that CMC@CMCS@OPs could help OPs achieve targeted and controlled release in the intestine. In addition, CMC@CMCS@OPs had no cytotoxicity on Caco-2 cells, and its apparent permeability coefficients increased 4.70-7.45 times compared with OPs, with the absorption rate increased by 129.38 %. Moreover, the transcytosis of CMC@CMCS@OPs nanogel occurred primarily through the macropinocytosis pathway, endocytosis pathway and intestinal efflux transporter-mediated efflux. Altogether, these results suggested that CMC@CMCS@OPs nanogel could be as an effective OPs delivery device for enhancing its stability and absorption.

Mining Xanthine Oxidase Inhibitors from an Edible Seaweed Pterocladiella capillacea by Using In Vitro Bioassays, Affinity Ultrafiltration LC-MS/MS, Metabolomics Tools, and In Silico Prediction.

The prevalence of gout and the adverse effects of current synthetic anti-gout drugs call for new natural and effective xanthine oxidase (XOD) inhibitors to target this disease. Based on our previous finding that an edible seaweed Pterocladiella capillacea extract inhibits XOD, XOD-inhibitory and anti-inflammatory activities were used to evaluate the anti-gout potential of different P. capillacea extract fractions. Through affinity ultrafiltration coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS), feature-based molecular networking (FBMN), and database mining of multiple natural products, the extract's bioactive components were traced and annotated. Through molecular docking and ADMET analysis, the possibility and drug-likeness of the annotated XOD inhibitors were predicted. The results showed that fractions F4, F6, F4-2, and F4-3 exhibited strong XOD inhibition activity, among which F4-3 reached an inhibition ratio of 77.96% ± 4.91% to XOD at a concentration of 0.14 mg/mL. In addition, the P. capillacea extract and fractions also displayed anti-inflammatory activity. Affinity ultrafiltration LC-MS/MS analysis and molecular networking showed that out of the 20 annotated compounds, 8 compounds have been previously directly or indirectly reported from seaweeds, and 4 compounds have been reported to exhibit anti-gout activity. Molecular docking and ADMET showed that six seaweed-derived compounds can dock with the XOD activity pocket and follow the Lipinski drug-like rule. These results support the value of further investigating P. capillacea as part of the development of anti-gout drugs or related functional foods.

Quinolinones Alkaloids with AChE Inhibitory Activity from Mangrove Endophytic Fungus Penicillium citrinum YX-002.

Acetylcholinesterase (AChE) inhibitory activity-guided studies on the mangrove-derived endophytic fungus Penicillium citrinum YX-002 led to the isolation of nine secondary metabolites, including one new quinolinone derivative, quinolactone A (1), a pair of epimers quinolactacin C1 (2) and 3-epi-quinolactacin C1 (3), together with six known analogs (4-9). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, and compared with data in the literature. The absolute configurations of compounds 1-3 was determined by combination of electronic circular dichroism (ECD) calculations and X-Ray single crystal diffraction technique using CuKα radiation. In bioassays, compounds 1, 4 and 7 showed moderate AChE inhibitory activities with IC50 values of 27.6, 19.4 and 11.2 µmol/L, respectively. The structure-activity relationships (SARs) analysis suggested that the existence of carbonyl group on C-3 and the oxygen atom on the five-membered ring were beneficial to the activity. Molecular docking results showed that compound 7 had a lower affinity interaction energy (-9.3 kcal/mol) with stronger interactions with different sites in AChE activities, which explained its higher activities.

The Ethnopharmacological, Phytochemical, and Pharmacological Review of Euryale ferox Salisb.: A Chinese Medicine Food Homology.

Euryale ferox Salisb. (prickly water lily) is the only extent of the genus Euryale that has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on their abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literature (since 1980), medical classics, database, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for further research and development of EFS-derived functional products.

The screening for marine fungal strains with high potential in alkaloids production by in situ colony assay and LC-MS/MS based secondary metabolic profiling.

Background: Alkaloids are the second primary class of secondary metabolites (SMs) from marine organisms, most of which have antioxidant, antitumor, antibacterial, anti-inflammatory, and other activities. However, the SMs obtained by traditional isolation strategies have drawbacks such as highly reduplication and weak bioactivity. Therefore, it is significantly important to establish an efficient strategy for screening strains and mining novel compounds. Methods: In this study, we utilized in situ colony assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the strain with high potential in alkaloids production. The strain was identified by genetic marker genes and morphological analysis. The secondary metabolites from the strain were isolated by the combine use of vacuum liquid chromatography (VLC), ODS column chromatography, and Sephadex LH-20. Their structures were elucidated by 1D/2D NMR, HR-ESI-MS, and other spectroscopic technologies. Finally, these compounds bioactivity were assay, including anti-inflammatory and anti-ß aggregation. Results: Eighteen marine fungi were preliminarily screened for alkaloids production by in situ colony assay using Dragendorff reagent as dye, and nine of them turned orange, which indicated abundant alkaloids. By thin-layer chromatography (TLC), LC-MS/MS, and multiple approaches assisted Feature-Based Molecular Networking (FBMN) analysis of fermentation extracts, a strain ACD-5 (Penicillium mallochii with GenBank accession number OM368350) from sea cucumber gut was selected for its diverse alkaloids profiles especially azaphilones. In bioassays, the crude extracts of ACD-5 in Czapek-dox broth and brown rice medium showed moderate antioxidant, acetylcholinesterase inhibitory, anti-neuroinflammatory, and anti-ß aggregation activities. Three chlorinated azaphilone alkaloids, compounds 1-3 (sclerotioramine, isochromophilone VI, and isochromophilone IX, respectively), were isolated from the fermentation products of ACD-5 in brown rice medium guided by bioactivities and mass spectrometry analysis. Compound 1 had shown remarkable anti-neuroinflammatory activity in liposaccharide induced BV-2 cells. Conclusion: In summary, in situ colony screening together with LC-MS/MS, multi-approach assisted FBMN can act as an efficient screening method for strains with potential in alkaloids production.

Hizikia fusiforme functional oil (HFFO) prevents neuroinflammation and memory deficits evoked by lipopolysaccharide/aluminum trichloride in zebrafish.

Background: Oxidative stress, cholinergic deficiency, and neuroinflammation are hallmarks of most neurodegenerative disorders (NDs). Lipids play an important role in brain development and proper functioning. Marine-derived lipids have shown good memory-improving potentials, especially those from fish and microalgae. The cultivated macroalga Hizikia fusiforme is healthy food and shows benefits to memory, but the study is rare on the brain healthy value of its oil. Previously, we had reported that the Hizikia fusiforme functional oil (HFFO) contains arachidonic acid, 11,14,17-eicosatrienoic acid, phytol, and other molecules displaying in vitro acetylcholinesterase inhibitory and nitroxide scavenging activity; however, the in vivo effect remains unclear. In this study, we further investigated its potential effects against lipopolysaccharides (LPS)- or aluminum trichloride (AlCl3)-induced memory deficiency in zebrafish and its drug-related properties in silica. Methods: We established memory deficit models in zebrafish by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS) (75 ng) or aluminum trichloride (AlCl3) (21 µg), and assessed their behaviors in the T-maze test. The interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), acetylcholine (ACh), and malondialdehyde (MDA) levels were measured 24 h after the LPS/AlCl3 injection as markers of inflammation, cholinergic activity, and oxidative stress. Furthermore, the interaction of two main components, 11,14,17-eicosatrienoic acid and phytol, was investigated by molecular docking, with the important anti-inflammatory targets nuclear factor kappa B (NF-κB) and cyclooxygenase 2 (COX-2). Specifically, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of HFFO were studied by ADMETlab. Results: The results showed that HFFO reduced cognitive deficits in zebrafish T-maze induced by LPS/AlCl3. While the LPS/AlCl3 treatment increased MDA content, lowered ACh levels in the zebrafish brain, and elevated levels of central and peripheral proinflammatory cytokines, these effects were reversed by 100 mg/kg HFFO except for MDA. Moreover, 11,14,17-eicosatrienoic acid and phytol showed a good affinity with NF-κB, COX-2, and HFFO exhibited acceptable drug-likeness and ADMET profiles in general. Conclusion: Collectively, this study's findings suggest HFFO as a potent neuroprotectant, potentially valuable for the prevention of memory impairment caused by cholinergic deficiency and neuroinflammation.

Heterophyllin B, a cyclopeptide from Pseudostellaria heterophylla, improves memory via immunomodulation and neurite regeneration in i.c.v.Aß-induced mice.

Pseudostellaria heterophylla, has historically been used as medicine food homology plant for thousand years in China. Our previous studies had indicated that daily intake of Pseudostellaria heterophylla extract enhanced cognitive memory. Herein, heterophyllin B (HET-B), a brain permeable cyclopeptide from Pseudostellaria heterophylla was determined, and the molecular mechanism underlying its memory improvement effects was investigated. Pseudostellaria heterophylla extract as well as HET-B reversed Aß25-35-induced axonal atrophy and neuronal apoptosis in cultured cortical neurons of mice. HET-B could enhance memory retrieval, modulate splenic T helper cell, and ameliorate neuroinflammation in i.c.v. Aß1-42 injected Alzheimer's disease (AD) mice. To explore the mechanism of action, network pharmacology was performed to predict protein targets and pathways of HET-B against AD. Five key targets were identified related to the effect of HET-B in AD intervention, and were clarified involved in axonal regeneration. We revealed for the first time that HET-B promoted memory retrieval through axonal regeneration and anti-neuroinflammation. This study provides a basis to research on HET-B as nutritional supplements for brain healthy.

Secondary Metabolite Variation and Bioactivities of Two Marine Aspergillus Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS.

Co-culture is known as an efficient way to explore the metabolic potential of fungal strains for new antibiotics and other therapeutic agents that could counter emerging health issues. To study the effect of co-culture on the secondary metabolites and bioactivities of two marine strains, Aspergillus terreus C23-3 and Aspergillus. unguis DLEP2008001, they were co-cultured in live or inactivated forms successively or simultaneously. The mycelial morphology and high-performance thin layer chromatography (HPTLC) including bioautography of the fermentation extracts were recorded. Furthermore, the agar cup-plate method was used to compare the antimicrobial activity of the extracts. Based on the above, liquid chromatography-photodiode array-tandem mass spectrometry (LC-PDA-MS/MS) together with Global Natural Products Social molecular networking (GNPS) and multiple natural products database mining were used to further analyze their secondary metabolite variations. The comprehensive results showed the following trends: (1) The strain first inoculated will strongly inhibit the growth and metabolism of the latter inoculated one; (2) Autoclaved A. unguis exerted a strong inducing effect on later inoculated A. terreus, while the autoclaved A. terreus showed high stability of its metabolites and still potently suppressed the growth and metabolism of A. unguis; (3) When the two strains are inoculated simultaneously, they both grow and produce metabolites; however, the A. terreus seemed to be more strongly induced by live A. unguis and this inducing effect surpassed that of the autoclaved A. unguis. Under some of the conditions, the extracts showed higher antimicrobial activity than the axenic cultures. Totally, A. unguis was negative in response but potent in stimulating its rival while A. terreus had the opposite effect. Fifteen MS detectable and/or UV active peaks showed different yields in co-cultures vs. the corresponding axenic culture. GNPS analysis assisted by multiple natural products databases mining (PubChem, Dictionary of Natural Products, NPASS, etc.) gave reasonable annotations for some of these peaks, including antimicrobial compounds such as unguisin A, lovastatin, and nidulin. However, some of the peaks were correlated with antagonistic properties and remain as possible novel compounds without mass or UV matching hits from any database. It is intriguing that the two strains both synthesize chemical 'weapons' for antagonism, and that these are upregulated when needed in competitive co-culture environment. At the same time, compounds not useful in this antagonistic setting are downregulated in their expression. Some of the natural products produced during antagonism are unknown chlorinated metabolites and deserve further study for their antimicrobial properties. In summary, this study disclosed the different responses of two Aspergillus strains in co-culture, revealed their metabolic variation, and displayed new opportunities for antibiotic discovery.

Marine fungal metabolite butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish.

BACKGROUND: Mounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in vitro neuroprotectant and inflammation inhibitor. However, little is known regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases. METHODS: Here, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl3) (21 µg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl3 injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl3 and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab. RESULTS: BTL-I dose-dependently ameliorated AlCl3-induced cognitive deficits in zebrafish. While AlCl3 treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brains of zebrafish, these effects, except GSH reduction, were reversed by 25-100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl3 decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles. CONCLUSIONS: The present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance.

Novel insight into the role of processing stages in nutritional components changes and characteristic flavors formation of noble scallop Chlamys nobilis adductors.

Processing stages play critical role in the nutrition and flavor changes of marine products. This study investigated the nutrition and flavor profiles in noble scallop Chlamys nobilis adductor during boiling, rinsing, baking and drying processing stages by high performance liquid chromatography, headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry. The results showed that the overall processing stages favorably preserved the essential amino acids. Drying obviously increased the umami and sweet amino acids contents by 72.08%, 67.77%, respectively (P < 0.05), and promoted the production of flavor nucleotides. In addition, the overall processing stages significantly increased the protein and lipid oxidation degree by (1.49-3.01)-fold and (4.25-5.81)-fold, respectively, compared with raw group (P < 0.05). Moreover, alcohols were the major volatiles in raw group, while the aldehydes, alcohols, and hydrocarbons predominated in rinsing, baking and drying stages. In conclusion, the processing maintained the nutrition value and improved the flavor of scallop adductors.

3D Printing of a PDMS Cylindrical Microlens Array with 100% Fill-Factor.

Cylindrical microlens arrays (CMLAs) play a key role in many optoelectronic devices, and 100% fill-factor CMLAs also have the advantage of improving the signal-to-noise ratio and avoiding stray-light effects. However, the existing preparation technologies are complicated and costly, which are not suitable for mass production. Herein, we propose a simple, efficient, and low-cost manufacturing method for CMLAs with a high fill-factor via the electric-field-driven (EFD) microscale 3D printing of polydimethylsiloxane (PDMS). By adjusting the printing parameters, the profile and the fill-factor of the CMLAs can be controlled to improve their optical performance. The optical performance test results show that the printed PDMS CMLAs have good image-projecting and light-diffraction properties. Using the two printing modes of this EFD microscale 3D-printing technology, a cylindrical dual-microlens array with a double-focusing function is simply prepared. At the same time, we print a series of specially shaped microlenses, proving the flexible manufacturing capabilities of this technology. The results show that the prepared CMLAs have good morphology and optical properties. The proposed method may provide a viable route for manufacturing large-area CMLAs with 100% fill-factor in a very simple, efficient, and low-cost manner.

Examining the practical limits of batch effect-correction algorithms: When should you care about batch effects?

Batch effects are technical sources of variation and can confound analysis. While many performance ranking exercises have been conducted to establish the best batch effect-correction algorithm (BECA), we hold the viewpoint that the notion of best is context-dependent. Moreover, alternative questions beyond the simplistic notion of "best" are also interesting: are BECAs robust against various degrees of confounding and if so, what is the limit? Using two different methods for simulating class (phenotype) and batch effects and taking various representative datasets across both genomics (RNA-Seq) and proteomics platforms, we demonstrate that under situations where sample classes and batch factors are moderately confounded, most BECAs are remarkably robust and only weakly affected by upstream normalization procedures. This observation is consistently supported across the multitude of test datasets. BECAs do have limits: When sample classes and batch factors are strongly confounded, BECA performance declines, with variable performance in precision, recall and also batch correction. We also report that while conventional normalization methods have minimal impact on batch effect correction, they do not affect downstream statistical feature selection, and in strongly confounded scenarios, may even outperform BECAs. In other words, removing batch effects is no guarantee of optimal functional analysis. Overall, this study suggests that simplistic performance ranking exercises are quite trivial, and all BECAs are compromises in some context or another.

Retinoic acid receptor-related orphan receptor RORα regulates differentiation and survival of keratinocytes during hypoxia.

Low O2 pressures present in the microenvironment of epidermis control keratinocyte differentiation and epidermal barrier function through hypoxia inducible factors (HIFs) dependent gene expression. This study focuses on investigating relations of the retinoic acid receptor-related orphan receptor alpha (RORα) to HIF-1α in keratinocytes under hypoxic conditions. The expression level of RORα is significantly elevated under hypoxia in both human and murine keratinocytes. Gene silencing of RORA attenuates hypoxia-stimulated expression of genes related to late differentiation and epidermal barrier function, and leads to an enhanced apoptotic response. While the hypoxic induction of RORα is dependent on HIF-1α, RORα is in turn critical for nuclear accumulation of HIF-1α and activation of HIF transcriptional activity. These results collectively suggest that RORα functions as an important mediator of HIF-1α activities in regulating keratinocyte differentiation/survival and epidermal barrier function during the oxygen sensing stage.

Understanding missing proteins: a functional perspective.

A missing protein (MP) is an unconfirmed genetic sequence for which a protein product is not yet detected. Currently, MPs are tiered based on supporting evidence mainly in the form of protein existence (PE) classification. As we discuss here, this definition is overly restrictive because proteins go missing in day-to-day proteomics as a result of low abundance, lack of sequence specificity, splice variants, and so on. Thus, we propose a broader functional classification of MPs that complements PE classification, discuss major causes, and examine three corresponding solution tiers: biological, technical, and informatics. We assert that informatics-driven solutions would have a major role in resolving the MP problem (MPP).