Search PubMedSearch

SEARCH · Search PubMed

Results for “outer membrane proteins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

500 records · Page 3Linked to original sources

Initial 4-Year Experience With Microaxial Flow Pumps Within a Tertiary Centre in Regional Australia.

BACKGROUND & AIM: The Microaxial Flow Pump (MFP) is a miniaturised rotary pump that aspirates blood from the left ventricle and expels it into the ascending aorta. It unloads the left ventricle and increases mean arterial pressure and cardiac output. MFP is most commonly utilised in cardiogenic shock, for protected percutaneous coronary intervention (PCI), and for ventricular offloading in veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHOD: We conducted a retrospective review of all patients who underwent MFP insertion at John Hunter Hospital, Australia. Categorical data are represented as counts and percentages, with continuous variables described as means with standard deviations. RESULTS: Twenty-three MFP devices were inserted between September 2020 and May 2024. Five (22%) were for protected PCI, three (13%) for venting with VA-ECMO (ECPELLA), and 15 (65%) for acute coronary syndrome (ACS) and cardiogenic shock. The median age for the overall cohort was 62 years, with a 74% male predominance. Eighty percent of the protected PCI cohort were elective outpatient procedures, and there were no deaths in this cohort. The mortality in the ECPELLA group was 67%. Thirteen (87%) of the patients with cardiogenic shock presented with an anterior infarct, and 53% had cardiac arrest on admission. The overall morality in the cardiogenic shock cohort was 40%. Complications in this cohort included limb ischaemia in four patients (17%) and site bleeding in seven patients (30%). Four patients (17%) required vascular surgery intervention. CONCLUSION: Our initial experience showed the use of MFP in a tertiary centre was safe and feasible, allowing progression from protected percutaneous intervention to acute cardiogenic shock.

Humans

Emergence of Babesia naoakii infection in Indonesian domestic cattle, a new host record in water buffaloes, and characterization of complete mitochondrial protein-coding genes.

Babesia (B.) naoakii, previously referred to as Babesia sp. Mymensingh, is a recently characterized tick-borne haemoprotozoan parasite of cattle. In Indonesia, we first reported its presence in 2022 from clinically affected cattle in Central Java. To investigate the wider epidemiology of this neglected ruminant-associated Babesia species, we surveyed apparently healthy cattle (Bos indicus) and water buffaloes (Bubalus bubalis) across three districts of Java, Indonesia. A PCR assay targeting the B. naoakii-specific apical membrane antigen 1 (ama1) gene detected the parasite occurrence in 34.39% of assessed cattle (87/253; 95% CI: 28.80-40.44%) and 30.77% of water buffaloes (12/39; 95% CI: 18.47-46.52%). These results represent the first record of B. naoakii infection in water buffaloes in the country and confirm that the parasite circulates in subclinically infected bovine hosts. To characterise this apicomplexan parasite further at the molecular level, we assembled in full length the three mitochondrial protein-coding genes (PCGs): cytochrome c oxidase subunits 1 (cox1) and 3 (cox3), as well as cytochrome b (cytb). These genes were reconstructed by next-generation sequencing of blood DNA collected during the acute haemolytic-phase of B. naoakii infection, from calves that subsequently succumbed to the disease in the endemic area. Phylogenetic analyses of the concatenated amino-acid sequences of cox1, cox3, and cytb placed the Indonesian isolates within a well-supported monophyletic clade, distinct from all previously characterised ruminant-associated Babesia species and sister to the Babesia bigemina/Babesia ovata lineage. This placement confirmed species identity and reinforced the genetic distinctiveness of B. naoakii in Indonesia. Notably, although B. naoakii circulates in peripheral blood and mirrors the diagnostic behaviour of the mild pathogen B. bigemina, its clinical impact more closely resembles that of the severe pathogenic B. bovis, particularly in young animals. This diagnostic-clinical discordance highlights the need for B. naoakii-specific molecular surveillance and species-level differentiation in regions of co-endemicity. Given the high prevalence in subclinically B. naoakii-infected adults, the documented severity of babesiosis in calves, and the potential for substantial economic losses, broader epidemiological investigations and species-specific control measures for B. naoakii are urgently performed. The same holds true for future epizootiological investigations of underdiagnosed B. naoakii-infections possibly circulating in Indonesian endemic ruminant bovids such as the banteng (Bos javanicus), the lowland anoa (Bubalus depressicornis) and the tamaraw (Bubalus mindorensis).

Animals

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (•OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated •OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. •OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of ∼1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. •OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following •OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt‑tolerant rootstock for pear, but its salt‑tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co‑expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss‑of‑function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival‑first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker‑assisted breeding of salt‑tolerant pear cultivars.

Salt Stress

Craniotomy versus Endoscopic Membranectomy in the Treatment of Non-Homogeneous Chronic Subdural Hematoma: A Pilot Randomized Parallel-Group Active-Controlled Trial (EMiT CSDH 2).

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition with persistent challenges related to recurrence. Endoscopic membranectomy (EM) has shown promising results in managing symptomatic non-homogenous (SNH)-CSDH, but comparative evidence against craniotomy with membranectomy (CM) is lacking. OBJECTIVES: To compare the safety and efficacy of EM versus CM in managing SNH-CSDH. MATERIALS AND METHODS: A pilot randomized parallel-group active-controlled open- labeled superiority trial from September 2023 to November 2024 at Government Kilpauk Medical College, Chennai, India. Sixty patients with SNH-CSDH were randomized into EM and CM groups. Recurrence was the primary outcome. Secondary outcomes included operative time, complications, radiological indices, pain, hospital stay, and functional recovery. All patients were followed for six months. RESULTS: No recurrence was observed in either group at six months. Two CM patients required reoperation on postoperative day one ( P = 0.15). EM was associated with shorter operative time ( P = 0.02), lower incidence of post-operative subdural residual fluid ( P = 0.015), better early hematoma reduction/subdural space reduction index ( P = 0.008), midline shift/symmetry improvement index ( P = 0.001), and lesser surgical site swelling ( P < 0.001). All patients were ambulant and had a Glasgow coma scale (GCS) 15 at discharge and at six months (including reoperated patients). Pain scores and functional recovery were comparable. EM patients had shorter hospital stays ( P = 0.004) and no significant complications. CONCLUSION: EM demonstrated favorable early radiological outcomes, fewer complications, and comparable functional recovery and recurrence versus CM in SNH-CSDH. Independent reproduction and larger multicentric trials are needed for validity and generalizability.

Humans

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000&#xa0;Hz, 95&#xa0;dB SPL, 2&#xa0;h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2&#xa0;weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1&#xa0;day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1&#xa0;day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals

Flap Versus Tunneling for Horizontal Ridge Augmentation With FDBA and i-PRF: A Randomized Controlled Clinical Trial.

AIM: This study evaluated the efficacy of conventional flap and tunneling techniques for horizontal alveolar ridge augmentation using freeze-dried bone allograft (FDBA) particles combined with injectable platelet-rich fibrin (i-PRF). MATERIALS AND METHODS: Forty-five patients were randomly allocated to one of three groups (n&#x2009;=&#x2009;15 each): conventional flap (CF), tunneling with membrane (TM), or tunneling without membrane (TnM). Preoperative ridge width was measured via cone beam computed tomography (CBCT). All augmentation procedures incorporated FDBA and i-PRF; an absorbable collagen membrane was applied in the CF and TM groups. Follow-up assessments, including CBCT imaging and histomorphometric analysis, were conducted 6&#x2009;months postoperatively. For normally distributed data, ANOVA with Tukey's post hoc test and paired samples t-test were applied. Non-normally distributed data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. RESULTS: Statistical analysis was performed on 43 patients. All groups demonstrated an increase in ridge width after 6&#x2009;months. At the 2&#x2009;mm level, the mean width gain was 1.28&#x2009;mm (95% CI: 0.17 to 2.40) in the TM group, 2.85&#x2009;mm (95% CI: 1.80 to 3.89) in the TnM group, and 1.95&#x2009;mm (95% CI: 1.07 to 2.83) in the CF group. However, statistical analysis revealed no significant intergroup variation (p&#x2009;>&#x2009;0.05). Histomorphometric assessments similarly demonstrated comparable outcomes across all groups, with no statistically significant differences observed (p&#x2009;>&#x2009;0.05). CONCLUSION: Within the limitations of this study, the tunneling technique, regardless of membrane use, appears to be a clinically viable alternative to the conventional flap method for horizontal alveolar ridge augmentation. However, further studies with longer follow-up periods are required to substantiate these findings. TRIAL REGISTRATION: irct.behdasht.gov.ir identifier: IRCT 20101204005305N21.

Humans

Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. METHODS: A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). RESULTS: A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. CONCLUSION: In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. TRIAL REGISTRATION: PROSPERO: CRD420261325458.

Humans

Ossicle occurrence characteristics and related molecular mechanisms in the sea cucumber Apostichopus japonicus.

To investigate the morphogenetic pattern and molecular mechanism of ossicle formation in the sea cucumber Apostichopus japonicus, this study systematically examined the morphological development and temporal sequence of spicules using the NaClO maceration method, in-situ squash preparation and microscopic observation. Comparative transcriptome sequencing was performed between doliolaria and pentactula larvae to screen differentially expressed genes (DEGs) related to ossicles formation, followed by pathway enrichment analysis. The function of the candidate key gene papilin-like was verified using siRNA-mediated gene silencing. The results were as follows: 1) Ossicles of A. japonicus first appeared at the late auricularia stage, initiating as X-shaped ossicles at the base of the oral tentacles. The number of X-shaped ossicles increased dramatically during the doliolaria stage. X-shaped ossicles were gradually replaced by table-shaped and rosette-shaped ossicles at the pentactula stage, suggesting that X-shaped ossicles may differentiate into these two ossicle types. The morphology of table-shaped ossicles showed a "simple-complex-simple" pattern with development. 2) Key genes related to ossicles formation, including CA1, COL1A2, and papilin-like, were identified by transcriptome analysis. After papilin-like knockdown, abnormal morphologies were observed in table-shaped ossicles of 1-year-old A. japonicus, such as spine-like protrusions on the outer margin of the disc and loss of table legs, confirming its crucial roles in maintaining ossicle morphology. This study clarified the morphological development pattern of ossicles in A. japonicus and identified a key regulatory gene (papilin-like) involved in ossicle morphogenesis, providing preliminary insights into the underlying molecular regulatory mechanism. These findings enrich our understanding on ossicles formation in echinoderms, and provide important morphological and molecular biological information for further studies on the developmental mechanism of ossicles in A. japonicus.

Animals

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-&#x3ba;B, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals

Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.

Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases. ATP1A4 encodes a testis-specific isoform of the Na+, K+-ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on Atp1a4 knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of ATP1A4 variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in ATP1A4, a missense variant (c.2578&#x2009;T>A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post-meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight ATP1A4 as a potential gene associated with human male infertility.

Male

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96&#xa0;h) and chronic (8&#xa0;weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals

Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article

Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8&#xa0;days to four thermal regimes: constant 18&#xa0;&#xb0;C (CT), constant 28&#xa0;&#xb0;C (HT), intermittent cooling from 18 to 8&#xa0;&#xb0;C followed by recovery to 18&#xa0;&#xb0;C (FL), and intermittent warming from 18 to 28&#xa0;&#xb0;C followed by recovery to 18&#xa0;&#xb0;C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P&#xa0;<&#xa0;0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans