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Acute gastroenteritis (AGE) is a common cause of pediatric emergency department (ED) visits and is frequently associated with dehydration and metabolic disturbances. Rapid assessment of electrolytes and glucose is essential in clinical management. Although venous blood gas analysis provides faster results, its agreement with standard serum biochemistry in pediatric AGE remains unclear. This retrospective observational study included children aged 1 month to 18 years who presented to the pediatric ED with AGE between January 1, 2024, and December 31, 2025, and underwent paired venous BGA and serum biochemical testing during the same visit. A total of 1853 paired measurements were obtained from 1191 patients, as some children contributed multiple paired measurements during repeated testing. Method comparison was performed according to Clinical and Laboratory Standards Institute (CLSI) EP09-A3 guidelines using intraclass correlation coefficients (ICC), paired comparisons, Pearson correlation, and Bland-Altman analysis. Both analyzers demonstrated acceptable intra-device reliability (ICC > 0.70). However, agreement between venous blood gas and serum biochemistry was poor for sodium, potassium, chloride, and glucose, with all inter-method ICC values below 0.70. Mean values differed significantly between methods for all parameters (P < .01). Bland-Altman analysis demonstrated wide limits of agreement (LOA) between the 2 methods; for example, glucose measurements showed a mean difference of 2.1 mg/dL with LOA ranging from -64.3 to 68.5 mg/dL. Venous blood gas electrolyte and glucose measurements are not interchangeable with serum biochemistry in children with acute gastroenteritis. While blood gas analysis may be useful for rapid screening or trend monitoring in urgent settings, confirmatory serum biochemical testing remains necessary for clinical decision-making in pediatric AGE.
The textile industry is a major source of water pollution worldwide, including many countries in the Global South. Effluents from washing, bleaching, and dyeing contain dyes, heavy metals, surfactants, and other toxic compounds that threaten ecosystems and human health. Although wastewater treatment plants (WWTPs) reduce pollution, they face high costs, sludge generation, and limited removal of persistent contaminants. To improve performance, physicochemical, biological, and hybrid technologies have been developed. Coagulation-flocculation and adsorption are cost-effective but produce secondary waste. Biological systems such as enzymatic treatment and microbial fuel cells enable pollutant removal with potential energy recovery, though scale-up remains limited. Emerging methods such as nanofiltration, nanobubble technology, and electrochemical advanced oxidation processes (AOPs) provide higher efficiencies but face material stability issues. This review examines current technologies, their mechanisms, limitations, and prospects for achieving effective, economical, and environmentally sustainable textile wastewater management, supported by an assessment of effluent quality compliance and techno-economic feasibility. The ultimate goals of the review are to identify major research gaps and treatment processes that are effective, scalable, and implementable in real textile wastewater treatment installations and to propose concrete research directions that will enable the translation of promising laboratory results to full-scale implementation for textile wastewater treatment.
Thunbergia laurifolia Lindl. (TL) is a medicinal herb belonging to the Acanthaceae family. It has been used in ethnomedicine and possesses many biological activities. This study aimed to optimize the extraction of rosmarinic acid (RA), a major active component of TL leaves, using an aqueous green solvent via stirring-assisted maceration (SAM). Butylene glycol (BG) was selected as the green solvent due to its safety and its ability to be incorporated directly into pharmaceutical and cosmetic formulations without requiring removal from the extract. A Box-Behnken design was employed to optimize the extraction of RA from TL leaves. The results demonstrated that extraction time and BG concentration were significant variables influencing the RA yield, total phenolic content, and antioxidant activity. The optimal condition was an extraction time of 2 h, 52% BG, and a stirring speed of 200 rpm. These parameters yielded 5.415 ± 0.023 mg/g TL RA yield, 2.573 ± 0.012 mg GAE/g TL total phenolic content, and 6.362 ± 0.097 mg AAE/g TL ABTS radical scavenging activity, closely to the predicted values. The extract obtained under the optimal condition exhibited anti-inflammatory properties. Furthermore, RA demonstrated wound-healing activity, and a biphasic dose-response was observed regarding its anti-melanogenic effects. These findings suggested the potential of the TL extract as a ready-to-use active ingredient for skincare and pharmaceutical formulations.
Here we present jammed interconnected bilayer emulsions (JIBEs) as a class of tissue-like materials with macroscopic scalability, comprising billions of bilayer-separated aqueous compartments per millilitre. These materials mimic the organizational structure and properties of biological tissues. Our self-assembly method generates up to decilitre-scale volumes of JIBEs within minutes. The process is highly adaptable to a wide range of amphiphiles, including lipids and block copolymers, providing flexibility in tailoring JIBEs for diverse applications. The jammed architecture of JIBEs imparts unique properties, such as direct extrusion 3D printability into aqueous solutions. Their membrane-bound structure allows functionalization with nanochannels, enabling the material to adopt the properties of the incorporated channels. In this study, we demonstrate three key features of JIBEs using distinct ion channels: tunable conductance, selective transport and memristance. We propose that functionalized JIBEs could unlock a broad range of applications, including separations, energy storage, neuromorphic computing, tissue engineering, drug delivery and soft robotics.
Polymer-mediated gene delivery is evolving from stochastic design methodologies to precise molecular engineering. Traditional polymers, although effective in nucleic acid complexation, face challenges in terms of structural heterogeneity, unpredictable pharmacokinetics and inefficient endosomal escape. These challenges have driven interest in sequence-defined polymeric systems, which enable atomic-level control over monomer composition, charge distribution and functionality. Sequence-defined polymers provide opportunities to establish robust structure-function relationships, overcome biological barriers and achieve targeted delivery to specific tissues. This Review examines the architectural evolution of polymeric gene carriers and highlights how increasing structural precision correlates with enhanced functional performance. Synthetic methodologies enabling sequence control are analysed, from solid-phase approaches to flow chemistry and supramolecular templating. By integrating polymer science with biological outcomes, we present a strategic framework for addressing persistent challenges in non-viral gene delivery.
Primary intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive extranodal lymphoma that rarely affects the prostate. Its nonspecific clinical and laboratory features often lead to misdiagnosis as benign prostatic hyperplasia (BPH) or prostatitis, delaying appropriate treatment. We report a case of primary prostatic IVLBCL initially misdiagnosed as BPH, highlighting the diagnostic challenges and the importance of comprehensive pathological evaluation. A 75-year-old male presented with a 1-year history of a weakened urinary stream, dribbling, increased nocturia, and urinary urgency. Symptoms transiently improved with self-medication of the α1-blocker tamsulosin but later recurred. Histopathological examination revealed clusters of atypical tumor cells within the prostatic vasculature. Immunohistochemistry showed positivity for leukocyte common antigen, Vimentin, CD20, and CD79a, with a Ki-67 index > 90%. A final diagnosis of primary intravascular large B-cell lymphoma of the prostate was established. Following diagnosis, the patient and his family declined any antitumor therapy (including chemotherapy) and opted for best supportive care and were discharged against medical advice. The patient died 5 months after diagnosis without receiving any subsequent antitumor therapy. Prostatic IVLBCL is a diagnostic mimic of BPH and requires a high index of suspicion. Immunohistochemistry and molecular studies are essential for accurate diagnosis. Early recognition and appropriate chemotherapy can improve outcomes in this rare malignancy.
Freezing injury during winter is a critical abiotic stress that severely impacts the growth, development and, fruit quality of deciduous fruit trees. Cold tolerance can be induced through seasonal cold acclimation, which involves coordinated adjustments in tissue structure, physiology, and biochemistry driven by natural low-temperature, with distinct strategies across plant species. However, the cold-tolerant mechanisms of pear trees during cold acclimation remain poorly understood. Here, one-year-old branches of 10 pear cultivar germplasms were evaluated for cold tolerance based on the semi-lethal low temperature (LT50), with three biological replicates across two consecutive experimental years (2021-2022). LT50 values varied significantly among these materials, ranging from -42.43 ℃ to -32.59 ℃ and exhibited a highly significant negative correlation with field freezing injury indices (r = 0.86091, p < 0.0001). Subsequently, integrating anatomical structure observation, physiological index determination, metabolomics, and transcriptomics (with three biological replicates, each with three technical replicates for all omics and molecular experiments), we compared the low-temperature stress responses of cold-resistant 'Shanli' and cold-sensitive 'Hanhong', with statistical validation via one-way ANOVA, Duncan's multiple range test, Pearson's correlation analysis, and gray relational analysis. The results demonstrated that with decreasing temperature, the xylem ratio and lignin content in 'Shanli' branches increased markedly compared to 'Hanhong', and overwintering capability was correlated with branch lignin synthesis (r = -0.7783, p < 0.01). Cold acclimation enhanced lignin accumulation in 'Shanli' branches by increasing guaiacyl (G) and syringyl (S) units, associated with increased activities of key enzymes (shikimate hydroxycinnamoyl transferase (HCT), caffeoyl shikimate esterase (CSE), ferulate 5-hydroxylase (F5H), cinnamyl alcohol dehydrogenase (CAD), peroxidase (POD)) and critical intermediate metabolites (phenylalanine, ferulic acid, sinapic acid) in the phenylpropanoid pathway. Transcriptomic analysis identified 75 differentially expressed genes (DEGs) (|log2FoldChange|≥1 and FDR < 0.05) mapped to the phenylpropanoid pathway. Five potential key genes from the HCT, CSE, F5H, CAD and POD gene families, together with their co-expressed genes (such as ERF105-like) were identified as potentially associated with lignin content and composition modulationce in pear branches, providing novel insights into the regulatory network of lignin synthesis under natur under cold stress. Our findings reveal relationships between lignin synthesis pathways and cold toleranal low-temperature stress and candidate genes for cold-resistant pear breeding.
Evodiamine (EVO), a major bioactive alkaloid isolated from Tetradium ruticarpum (A.Juss.) T.G.Hartley, possesses diverse pharmacological activities; however, its potential hepatotoxicity remains insufficiently characterized. This study aimed to evaluate the hepatotoxic effects of EVO and explore the molecular events associated with its toxicity. Male mice were administered EVO (10, 20, or 40 mg/kg) for 7, 14, or 28 days. EVO exposure caused dose- and time-dependent liver injury and oxidative stress, as shown by serum biochemistry, histopathology, and oxidative stress markers. An integrated multi-omics strategy combining network toxicology, transcriptomics, and metabolomics was applied to explore the underlying mechanisms. EVO exposure induced significant liver injury and oxidative stress in a dose- and time-dependent manner. Multi-omics analyses suggested that EVO treatment was associated with alterations in pathways related to inflammation, apoptosis, and lipid metabolism, including FOXO, PPAR, and NF-κB signaling pathways. Changes in the expression of SIRT1, CASP2, and FOXO3 and disturbances in glycerophospholipid metabolism were further observed. In conclusion, EVO induces dose- and time-dependent hepatotoxicity in mice. Multi-omics analyses suggest that inflammatory responses, apoptotic processes, and metabolic disturbances may contribute to EVO-induced liver injury. These findings provide toxicological evidence regarding the safety profile of EVO and identify biological pathways associated with its hepatotoxicity.
Artificial lipid droplets (aLDs) provide a controllable platform for studying lipid biochemistry, but their use is limited by contamination with other membrane structures and the lack of quantitative methods to assess sample purity. Here, we establish dithionite quenching of NBD-labeled lipids as a simple approach to evaluate aLD purity. The approach relies on dithionite's ability to selectively quench NBD fluorophores exposed in the phospholipid monolayer of aLDs and in the outer leaflet of liposome bilayers, but not those protected within the inner leaflet of liposome bilayers. Consistent with liposome contamination, bulk aLD preparations exhibit incomplete quenching, which can be separated by sucrose gradient centrifugation into liposome-like and droplet-enriched populations based on quenching behavior. Guided by this assay, sonication conditions were optimized to increase aLD purity and reduce liposome contamination. A biotin-streptavidin immobilization strategy further enabled stable imaging of individual aLDs. Finally, we applied dithionite quenching to probe the accessibility of neutral lipids within aLDs. This revealed hydrophobicity-dependent quenching kinetics of neutral lipids, with less hydrophobic diacylglycerols showing greater surface exposure within aLDs than more hydrophobic triacylglycerols and cholesterol esters. Taken together, these establish dithionite quenching of NBD-labeled lipids as a simple quantitative method for assessing aLD purity and demonstrate its utility for studying lipid accessibility.
The primary cause of poor prognosis in non-small cell lung cancer (NSCLC) patients is metastasis; however, little is known about the underlying mechanisms mediated by cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME). We conducted comprehensive molecular and cellular analyses, including RNA sequencing, immunohistochemistry, coculture experiments, and genetic mouse models, to investigate the role of the CD248-periostin-integrin β1 (ITGB1) axis in NSCLC metastasis. We demonstrated that CD248+ CAFs are key regulators of NSCLC metastasis. RNA sequencing and clinical sample analysis revealed that CD248 expression in CAFs was positively correlated with increased secretion of periostin (encoded by POSTN). In CAFs, elevated periostin expression is strongly linked to lymph node metastasis (p = 0.002), advanced tumor stage (p = 0.0039), and poor overall survival (p < 0.05) in patients with NSCLC. By promoting the nuclear translocation of YAP1 and regulating POSTN promoter activity to increase periostin expression, CD248 mechanistically causes YAP1 activation in CAFs. According to functional tests, CAFs secreted periostin binds to ITGB1 in NSCLC cells, triggering the FAK/Src signaling pathway to cause epithelial-mesenchymal transition (EMT)-like phenotypic changes and promote NSCLC cell invasion and migration. Additionally, periostin promotes collagen I deposition and increases extracellular matrix (ECM) stiffness, which further amplifies YAP1-driven periostin secretion from CD248+ CAFs, resulting in the formation of a prometastatic positive feedback loop. Fibroblast-specific CD248 deletion or POSTN knockout mice exhibit dramatically reduced metastatic tumor growth in NSCLC in vivo. This is accompanied by decreased ECM stiffness in the TME, decreased EMT-like phenotypic changes, and decreased collagen I deposition. Our results collectively suggested a CD248-YAP1-Periostin-ITGB1 axis that contributes to a prometastatic feedback loop in NSCLC, indicating that focusing on this axis may be a viable therapeutic approach to prevent NSCLC metastasis.
Our understanding of trypsin, its zymogenicity and its inhibition is intimately intertwined with the history of biochemistry. Early structural studies revealed its close relationship to chymotrypsin, with its active site triad, oxyanion hole and N-terminus involved in a buried salt bridge near the active site. Its complex with basic pancreatic trypsin inhibitor provided a model for how peptide substrates bind to and are cleaved by the proteinase. Analysis of crystals of trypsinogen by Wolfram Bode and Robert Huber revealed that a large region of the zymogen is disordered prior to proteolytic activation, with an associated disruption of the oxyanion hole and substrate binding pockets, highlighting the importance of disorder in protein function. As archetype of numerous therapeutically important serine proteinases, trypsin can also serve as a surrogate for structure-based drug design. Trypsin variants designed for ligand binding studies resulted however in an unexpected plasticity of the mutant proteins that underlines the complexity of protein stability. A trypsin variant selected for peptide ligation (reverse proteolysis) was shown to possess zymogen-like characteristics that proved central to its application in modification of therapeutic proteins. The review pays homage to the seminal works of Bode and Huber and their influence on modern structural biology.
Wound healing is a complicated biological process primarily involving tissue regeneration and repair. However, conditions such as infection, poor blood circulation, or long-term illnesses/chronic diseases (like diabetes) can impede the healing process and cause delayed recovery. In order to address these challenges, authors developed wafers. The prepared wafers have emerged as a promising solution due to their ease of application, excellent biocompatibility, and ability to maintain a moist wound environment. These porous, sponge-like systems can also be loaded with bioactive agents, enabling sustained and controlled drug delivery. The wafer was fabricated using solvent casting method with polymeric mixture of hydroxypropyl methyl cellulose (HPMC), ethyl cellulose (EC), and polyvinyl pyrrolidone (PVP K-30) and loaded with curcumin to promote wound healing. The loaded curcumin was dispersed using a high-speed homogeniser and lyophilized in a controlled environment. The developed wafer formulation was further characterised using scanning electron microscopy (SEM), thermogravimetry-differential thermal analysis (TG-DTA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), tensile strength analysis, swelling index, and water vapour transmission rate. The in vitro drug release study was carried out mimicking USP 5 paddle-over-disc type dissolution apparatus and the results indicated that the created wafers have a sustained drug release while keeping the tissue moist. The anti-microbial potential of wafers was confirmed using the disc diffusion method. The developed wafer showed strong potential as an antibacterial wound dressing, providing controlled drug release along with fast-acting relief from bacterial infections.
Bethencourtia palmensis (Nees) Choisy is an endemic plant of the Canary Islands, with different populations on La Palma and Tenerife, that contains biopesticidal compounds and whose endophytic fungi have also shown potential for biopesticide production. This study explores the metabolic and biopesticide potential of endophytic culturable fungi isolated from two island populations of Bethencourtia palmensis [Tenerife (T) and La Palma (P)]. The two plant populations showed distinct chemical profiles: 11β-acetoxy-5α-(angeloyloxy)silphinen-3-one and tetratriacontane were major components in T, while 5α-senecioyloxy-silphinen-3-one, tetratriacontane, and jacaranone were predominant in P. From potato dextrose agar (PDA) medium, 21 and 16 fungal isolates were obtained from T and P, respectively. Ethyl acetate extracts were tested against Myzus persicae, Meloidogyne javanica, Botrytis cinerea, and Fusarium verticillioides. Three isolates from T (14%), belonging to Aspergillus and Penicillium, showed bioactivity. In contrast, 13 isolates from the P population (81%) were bioactive and belonged to Alternaria, Aureobasidium, Aspergillus, Penicillium, and Stemphylium. Additional isolation from P using YES medium (2% yeast extract, 15% sucrose, 1.5% agar) yielded 31 new isolates, 20 of which (65%) were bioactive, including genera not recovered on PDA. Gas chromatography-mass spectrometry-based metabolite fingerprinting revealed distinctive patterns associated with specific genera. The findings highlight significant differences in the plant chemistry and bioactive endophytes between two island populations of B. palmensis. Furthermore, these strains are a promising source of bioactive compounds. The diverse range of bioactivities observed suggests high potential for the discovery of novel biopesticides with applications in sustainable agriculture. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Pomalidomide is a 2nd-generation chiral immunomodulatory (IMiDs) drugs and have antiangiogenic activity. Despite being teratogenic, it has been shown to be effective in treating multiple myeloma. Enantioselectivity, chemical structure, and biological activity have been investigated using molecular docking. In silico docking simulations to confirm the enantioselective binding of pomalidomide to immunomodulator targets, namely, CRBN, TNF- α11, Pg G/H synthase 2, and Cadeherin-5 Protein. The protein was preprocessed using hydrogen addition, disulphide treatment, and bond order assignment. The Ligand Preparation Module was used to optimize all of the chosen ligands, and OPLS3e Forcefield was used to optimize the geometry. Site map analysis module was used to determine the top-ranked receptor binding sites for the enzymes. Molecules were docked by using Schrodinger 2020_3 software. Docking study confirms the enantioselective binding of pomalidomide to immunomodulator targets (CRBN, TNF-α_11, Pg G/H synthase 2, and Cadeherin-5 Protein). Out of all four targets S- (-) enantiomer of pomalidomide had significant binding with CRBN and TNF-α 11, while R-(+)enantiomer of pomalidomide had significant binding with Pg G/H synthase 2, and Cadeherin-5 Protein. The result suggests that, chemical interactions of S-enantiomer of pomalidomide have better binding with residues at the active site of CRBN and TNF-α 11. This concludes that S-enantiomer of pomalidomide could be a better choice for multiple myeloma therapy.
Developing high-performance impact-stiffening polymers that are broadly applicable across chemical systems remains a key challenge, as existing designs rely on meticulously engineered molecular motifs. Inspired by water's role in biological impact resistance, we introduce a generalizable biomimetic paradigm. We transform water-commonly considered a property-limiting plasticizer-into an active, rate-sensitive cross-linker by structurally confining bound-water networks within proton-rich polymer scaffolds. Programming their dissociation kinetics enables a sharp, reversible soft-to-rigid transition under impact via kinetic freezing. This design, demonstrated in a poly(thioctic acid)-based system, concurrently achieves outstanding energy dissipation, self-healing, and strong adhesion. Crucially, it bypasses de novo synthesis of specialized motifs and is applicable across diverse polymer backbones, establishing programmable water dynamics as a versatile principle for adaptive polymeric materials.
The formation of fibrous architectures via peptide self-assembly underpins numerous biological functions and biomaterial applications; however, the thermodynamic origins of multistep assembly pathways remain elusive. Here, we map the complete free-energy landscape governing the liquid-liquid phase separation (LLPS)-mediated self-assembly of an amphiphilic peptide by exploiting temperature as a tunable parameter. We discover an unexpected thermodynamic mechanism: the initial LLPS-like clustering is enthalpy-driven but limited by a positive enthalpic barrier (+121 kJ mol-1), arising from the endothermic disruption of intramolecular hydrogen bonds before interpeptide contacts can form. Subsequent nucleation and fibril growth are governed by negative entropic barriers (-56 and -39 kJ mol-1, respectively), reflecting the reorganization cost of partially ordered oligomers. The energy landscape identifies LLPS as the rate-limiting step with the highest Gibbs free-energy barrier (+26 kJ mol-1). Our findings establish a generalizable framework for decoding multistep biomolecular self-organization, with implications for designing adaptive biomaterials and understanding aberrant phase transitions in diseases.
Fluoride is abundant in the Earth's crust but is rarely used by biological systems and is toxic inside cells. Most prokaryotic genomes contain genes encoding fluoride export channels, known as CrcB, or fluoride/proton antiporters, known as CLCF. Prokaryotes rely on one type only. In this study, Pseudomonas putida ATCC 12633 that natively expressed a chromosomally-encoded CrcB was engineered with plasmids containing a CLCF exporter gene. The addition of CLCF and subsequent adaptive evolution made the cells resistant to > 500 mM sodium fluoride and able to degrade 150 mM 2-fluoropropionic acid and export 150 mM fluoride. In the absence of CLCF and adaption, only 1 mM 2-fluoropropionic was degraded and culture density decreased. The adaption of multiple cell lines occurred uniformly. All increased their CLCF gene copy and incurred mutations in the native CrcB. Two of those point mutations and a designed deletion were introduced into the unadapted wild-type strain and confirmed as CrcB knockouts. In total, the CLCF antiporter was selected for under the conditions used and was necessary for biodegrading high concentrations of an organofluorine compound. Sustaining viability at high fluoride levels is relevant for engineering prokaryotes to biodegrade fluorinated chemicals and installing fluoride into compounds by biosynthesis.
Human cytoplasmic leucyl-tRNA synthetase (LARS) is known to catalyze the ligation of leucine to tRNALeu during protein biosynthesis. However, LARS also acts as a nutrient sensor in a non-canonical activity to regulate cell growth. In this investigation, LARS was determined to be expressed at high levels in human liver cancer, which correlated with poor clinical outcomes in patients. Knockdown of LARS in HepG2 liver cancer cells suppressed cell proliferation and growth, yet promoted cell migration, without affecting global protein translation. Using data from RNA sequencing, differentially expressed genes in response to LARS knockdown were significantly clustered in the cellular senescence pathway. Elevated p21 and p16 expression with increased senescence-associated β-galactosidase activity was observed in LARS knockdown HepG2 cells. In addition, autophagy with increasing autophagic flux was triggered in LARS knockdown HepG2 cells. Furthermore, the depletion of LARS induced oxidative stress with increased production of reactive oxygen species and decreased mitochondrial membrane potential. Importantly, re-expression of shRNA-resistant LARS largely rescued the senescence, autophagy, and oxidative stress caused by LARS knockdown, confirming the specificity of these effects. These findings suggest that LARS plays a role in regulating liver cancer cell proliferation via multiple cellular responses and may serve as a promising therapeutic target in liver cancer.
Ecosystem function and stability are often positively related to species richness in experiments, but in nature, abiotic gradients may over-ride or obscure the effects of richness on function and stability. In addition, community stability may be driven by distinct mechanisms along diversity or abiotic gradients and exhibit different responses to differing degrees of variability in an abiotic condition. We explored relationships between salinity, plant diversity, ecosystem function (annual biomass production), and stability of biomass over 25 years for seven coastal marsh plant communities arranged across an estuarine salinity gradient in Georgia, USA. In contrast to expectations, neither plant biomass nor its stability was related to species richness. Plant richness was positively correlated to within-year high tide salinity range and peaked at intermediate values of mean salinity. Biomass stability was negatively correlated with mean salinity but was unrelated to salinity range. Stability was driven by dominant species at sites with low richness, but asynchrony likely contributes to stability at intermediate salinity sites with higher diversity. Our results illustrate the importance of studying variability in abiotic conditions in addition to their mean and demonstrate that stability and richness may not necessarily be correlated in nature due to underlying abiotic gradients affecting both.
Hypersensitivity pneumonitis (HP) manifests as fibrotic (FHP) and non-fibrotic (NFHP) phenotypes. Clinically distinguishing FHP from idiopathic pulmonary fibrosis (IPF) remains challenging owing to phenotypic overlap, despite divergent management protocols. This investigation sought to develop a plasma proteomics-based framework for differential diagnosis between these entities. A total of 119 subjects were enrolled from the Chinese Interstitial Lung Disease (ILD) National Cohort and the PORTRAY IPF Cohort between July 2018 and June 2022, comprising 32 healthy controls (HCs), 31 NFHPs, 28 FHPs, and 28 IPF patients. The plasma samples were subject to quantitative proteomic profiling, weighted gene co-expression network analysis (WGCNA), and bioinformatics analysis to identify differentially expressed proteins, core pathways, and co-expression modules. Key proteins were selected to construct and validate diagnostic models via seven machine learning algorithms. This study delineated the plasma proteomic landscape of FHP and IPF, identifying 813 proteins. WGCNA revealed significant enrichment of the glycolysis/gluconeogenesis and pyruvate metabolism pathways, implicating metabolic reprogramming in FHP pathogenesis. Differential analysis identified nine differentially expressed proteins, from which a six-protein signature (H2BC12, SHBG, APCS, PTPRG, IGHV1-58, and GAPDH) was derived through LASSO regression and recursive feature elimination. Among seven machine learning algorithms, support vector machine (SVM) achieved the optimal performance on the independent test set with an accuracy of 71.4%, effectively discriminating FHPs from IPFs. This model represents a promising non-invasive molecular tool for the differential diagnosis of atypical interstitial lung diseases. This study established the plasma proteomic landscape of FHP, linking metabolic reprogramming to disease pathogenesis and providing a machine learning framework for biomarker-guided differential diagnosis.