This study examined the effect of frailty on social isolation among elderly prostate cancer patients, focusing on the chain mediating roles of illness perception and acceptance of illness. Additionally, a network analysis was conducted to explore the internal interconnections between illness perception and acceptance of illness. Descriptive quantitative study. A total of 288 elderly prostate cancer patients were recruited from a major public hospital in Wenzhou. The study investigated participants' baseline information, frailty, illness perception, acceptance of illness, and social isolation. Chain mediation analysis was conducted using SPSS 26.0 and the PROCESS Macro, whereas partial correlation network analysis was performed in R. Frailty, illness perception, and acceptance of illness were all significantly associated with social isolation. The link between frailty and social isolation was sequentially mediated by illness perception and acceptance of illness, explaining 61% of the total variance. Among these factors, acceptance of illness exerted the strongest effect. Network analysis further indicated the interrelationship between illness perception and acceptance of illness. This study highlights the importance of addressing frailty, illness perception, and acceptance of illness in clinical nursing practice, which may help reduce social isolation among prostate cancer patients. Recognizing frailty, alleviating negative illness perceptions, and enhancing illness acceptance may help prevent social isolation related to illness. This study provides a theoretical basis for elucidating the mechanisms of social isolation and provides precise targets for clinical intervention. Nurses can integrate various treatment approaches from these views to enhance the health and well-being of elderly prostate cancer patients. The STROBE guidelines were followed. Patients contributed by completing the questionnaire, ensuring the accuracy and completeness of the information with assistance from the research team.
Precise control of local conformational bias is essential for constructing stimulus-responsive aromatic architectures. Amide-derived scaffolds such as squaramides are particularly attractive targets, as their moderate rotational barriers allow thermodynamic tuning without irreversible locking. Here we demonstrate that introduction of a hydrogen-bond-accepting side chain enables thermodynamic programming of squaramide conformations. The triethylene glycol (TEG) substituent of squaramide 1c bearing a pyrene moiety induces reversible temperature-dependent switching between (trans, trans) and (cis, trans) forms, which can be quantified by variable-temperature NMR and van't Hoff analysis (ΔH° = -1.87 kcal mol-1, ΔS° = -8.2 cal mol-1 K-1). In contrast, N-n-propyl analogue 1b lacking a hydrogen-bond-accepting functionality exists exclusively in (cis, trans) form under identical conditions, establishing the minimal structural requirement for switching. A diphenyl analogue 1d without π-extension retains thermally reversible behavior, demonstrating that π-surface enlargement is not essential, but modulates conformational bias. These results establish a side-chain-enabled design principle for thermodynamically programmable aromatic conformations.
Mood disorders, including major depressive disorder, bipolar disorder, generalized anxiety disorder, and posttraumatic stress disorder, constitute a primary source of global disability, and with conventional monoamine-targeted pharmacotherapy, approximately one-third of patients remain with treatment-resistant disease. Over the past decade, the microbiota-gut-brain axis (MGBA) has emerged as a systems-level pathophysiological framework that explains the chronic neuroinflammation, hypothalamic-pituitary-adrenal axis hyperactivity, and impaired neuroplasticity that characterize treatment-resistant mood disorders. Short-chain fatty acids (SCFAs) are key molecular mediators in MGBA signaling, exerting epigenetic regulation through the inhibition of histone deacetylase, suppression of microglial toll-like receptor 4/nuclear factor-kappa B signaling, reinforcement of intestinal and blood-brain barrier integrity, and rebalancing of tryptophan-kynurenine metabolism. A few small randomized controlled trials and meta-analyses have reported that restoring SCFA output using next-generation psychobiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila, and Clostridium butyricum), prebiotic-rich dietary patterns, defined synbiotics, and direct postbiotic supplementation is associated with symptom improvement, although the evidence base remains preliminary, and have been proposed as candidate prognostic biomarkers. This narrative review synthesizes 2022 to 2026 mechanistic and clinical evidence on SCFA-producing psychobiotics in mood disorders; integrates these findings within a clinical nutrition framework that positions dietary fiber, microbiota-accessible carbohydrates, and targeted psychobiotic supplementation as legitimate adjuncts to conventional psychopharmacology; and discusses the translational challenges of strain specificity, dosing variability, and precision-psychobiotic medicine. Nevertheless, current evidence remains dominated by preclinical models, with human trials constrained by size, duration, and number.
Online physical education has become an important mode of instruction in higher education; however, insufficient student engagement remains a critical concern. This study aimed to examine the associations between academic self-efficacy and college students' learning engagement in online physical education, and tested the serial mediating roles of learning motivation and self-control. A cluster sampling method was used to recruit 898 undergraduate students (502 males and 396 females) from two universities. Academic self-efficacy, learning motivation, self-control, and online physical education engagement were assessed using validated scales. Data were analyzed using descriptive statistics, correlation analysis, and tests of serial mediation. The results indicated that: (1) academic self-efficacy was significantly and positively correlated with learning motivation, self-control, and online physical education learning engagement (r = 0.322, p < 0.001; r = 0.385, p < 0.001; r = 0.325, p < 0.001); (2) Learning motivation and self-control each played independent mediating roles in the relationship between academic self-efficacy and engagement in online physical education.; and (3) learning motivation and self-control jointly formed a serial mediation pathway between academic self-efficacy and online physical education engagement. These findings suggest that academic self-efficacy is associated with engagement in online physical education via pathways involving learning motivation and self-control. The results suggest that academic self-efficacy, learning motivation, and self-control are associated with higher levels of engagement in online physical education.
In the global post-antibiotic era, effective alternatives to in-feed antibiotics are urgently needed. This study evaluated a blend of natural molecules of monopropionin, monobutyrin, and monolaurin as an antibiotic alternative in weaned piglets. A total of 180 weaned piglets (Duroc × Landrace × Yorkshire; 24 ± 1 d) were randomly assigned to five dietary treatments for 42 days: control (CON, basal diet), antibiotic (ANTI, basal diet + 500 mg/kg enramycin), and three doses (T1: 600, T2: 1,000, T3: 1,400 mg/kg) of the blend. Growth performance, diarrhea incidence, serum biochemistry, immunity, nutrient digestibility, and fecal microbiota were assessed. Compared with CON, both ANTI and T2 significantly increased final body weight and average daily gain (p < 0.01), and reduced feed-to-gain ratio (p < 0.05). Diarrhea rate was significantly decreased in ANTI, T2, and T3 (p < 0.01). T2 also elevated serum total protein, albumin, and total antioxidant capacity (p < 0.05) without increasing alanine aminotransferase activity, and enriched beneficial gut bacteria (Lactobacillus and Eubacterium) (p < 0.05). In contrast, the lowest dose (T1) showed no significant effects on growth or diarrhea, while the highest dose (T3) reduced diarrhea but did not improve growth performance. In conclusion, dietary supplementation with 1,000 mg/kg of this blend effectively improved growth performance, enhanced antioxidant capacity, and modulated gut microbiota in weaned piglets, demonstrating promising potential as an antibiotic alternative.
Polymer electrode materials (PEMs), characterized by tunable and flexible molecular structures, hold great promise for potassium storage. However, their practical implementation is hindered by inherently low electrical conductivity. Herein, we synthesize a novel bioinspired neuron-like networks by controllably grafting conjugated polymer nanofilaments onto MXene nanosheets (denoted as CMP@BrMXene). This distinctive neuron-like architecture, along with the resulting cytoplast-like MXene junctions, not only creates abundant continuous pathways in multiple directions to facilitate rapid and uniform electron transport, but also exposes additional active sites for K+ coordination within the polymer-based anode. Leveraging these unique structures, the CMP@BrMXene electrodes deliver a high reversible specific capacity of 525 mAh g-1 at 30 mA g-1 and exhibit outstanding rate capability, retaining 119.8 mAh g-1 at 3000 mA g-1. Impressively, a durable capacity retention of 88.4% is maintained after 3000 cycles at 1 A g-1. Furthermore, operando XPS and theoretical analysis provide new insights into the redox reaction mechanism, confirming that MXene can streamline the multi-electron redox process and enhance the utilization of redox-active sites. These findings underscore that the all-integrated CMP@BrMXene electrodes, with MXene serving as multifunctional junctions, establish a new paradigm for developing high-performance potassium storage anodes.
Tough adhesives require efficient bulk energy dissipation, yet the molecular design principles for achieving this without sacrificing adhesion strength remain a challenge. Here, we report a chain-length regulation strategy for UV-curable acrylate adhesives, in which long polymer strands between cross-linking points generate effective entanglements, thereby promoting bulk energy dissipation during debonding. The resulting adhesives achieve exceptional adhesion strength (23.13 MPa) and ultrahigh adhesion toughness (36.77 kJ m-2). Fracture measurements and digital image correlation show that the long-chain entangled network markedly increases bulk fracture energy by delocalizing crack-tip strain into an enlarged deformation process zone and retarding crack propagation. Chain-dynamics and chain-conformation analyses further confirm the role of entanglement by revealing a broader relaxation spectrum and a much larger releasable conformational length in the long-chain network that enhances bulk energy dissipation. We further demonstrate its application potential and excellent long-term environmental stability, together with a physics-informed prediction of long-term adhesion retention across practical service temperatures. These results establish chain-length regulation as an effective molecular design strategy for strong and tough adhesives.
Exposure to food advertising is associated with consumption. Globally, most outdoor food advertisements feature unhealthy foods or beverages. As Australian local government areas (LGAs) begin developing restriction policies, the feasibility of applying nutrient-based Nutrition Classification Systems to outdoor advertising requires evaluation. Observational study on 1) types of food business advertisements outdoors and 2) availability of quantitative nutrition and/or ingredient information for featured products. 178 outdoor advertisements were analysed, from a 500m audit around schools in 16 stratified LGAs (2019), along with bus shelter audits in four LGAs (2022). Advertisements were categorised as featuring 'branded packaged products', 'food service product - chain', 'food service product - independent', 'branding only', or 'incidental food/beverage'. For packaged or food service advertisements, online searches were conducted to identify product-specific nutrition information. Metropolitan Perth, Australia. Advertisements featured packaged products (34% of advertisements); food service products - chain (21%); independent (16%); incidental food/beverage (18%); and branding only (11%). Nutrition information was located for 70% of packaged products and 68% of chain food service advertisements. Independent food service outlets provided no nutrition data and rarely depicted identifiable products. Overall, nutrition information was available for 45% of advertisements, and ingredient information for 35%. The limited availability of quantitative data constrains the application of nutrient-based nutrition classification systems. A system based primarily on food categories, with nutrient limits for some categories, and a robust approach to brand advertising likely offers a practical and impactful approach for LGAs seeking to restrict unhealthy outdoor food advertising.
POLG (DNA polymerase γ catalytic subunit)-related mitochondrial diseases are among the most severe primary mitochondrial disorders and are characterized by progressive neurodegeneration with prominent dopaminergic involvement. However, the cell type-specific mechanisms linking mitochondrial DNA instability to neuronal vulnerability remain incompletely defined. Using patient-derived midbrain organoids and single-cell RNA sequencing, we investigated how POLG mutations alter mitochondrial and neuronal programs at subtype resolution. We analyzed dopaminergic neuronal populations and ventral midbrain neurons to define disease-associated transcriptional changes. To evaluate therapeutic improvement, POLG organoids were treated chronically with nicotinamide riboside (NR), followed by single-cell transcriptomic profiling and pathway enrichment analysis. POLG mutations induced a coordinated downregulation of genes associated with oxidative phosphorylation and synaptic signaling, particularly in terminally differentiated dopaminergic neurons. This transcriptional alteration involved genes encoding respiratory chain complexes I-V, mitochondrial translation machinery, and ATP synthase components, suggesting disruption of mitochondrial bioenergetic programs at the transcriptomic level. Among dopaminergic subtypes, DA2 neurons and ventral midbrain neurons showed the most pronounced transcriptional alterations, indicating maturation-dependent vulnerability. NR treatment was associated with altered expression of genes involved in oxidative phosphorylation, NADH dehydrogenase activity, respiratory chain assembly, and synaptic pathways. Following NR exposure, dopaminergic subpopulations exhibited changes in cell-type proportions and partial normalization of mitochondrial- and synaptic-related transcriptional programs. These findings identify transcriptional alterations in pathways related to mitochondrial respiration. The data further suggests that modulation of NAD⁺ metabolism is associated with transcriptional changes in mitochondrial and neuronal pathways in this disease context.
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that have attracted growing concern owing to their widespread presence in drinking water and limited removal by conventional remediation technologies. This challenge has driven increasing interest in porous materials capable of selectively removing PFAS under environmentally relevant conditions. Among these, zirconium-based metal-organic frameworks (MOFs) have shown great potential for water-related applications due to their chemical and hydrolytic stability. In this work, we report the design, synthesis, and characterization of two UiO-68-type mixed-linker MOFs, UiO-68-SSeS and UiO-68-TzSeTz, incorporating selenophene-based heteroaromatic dicarboxylate linkers through a solvent-assisted linker exchange strategy. The heterocyclic linkers 5,5'-(selenophene-2,5-diyl)-bis-(thiophene-2-carboxylate) (H2SSeS) and 2,2'-(selenophene-2,5-diyl)-bis-(thiazole-5-carboxylate) (H2TzSeTz) were successfully embedded within UiO-68 while preserving its fcu topology. The performance of the two MOFs as sorbents toward PFAS in tap water was evaluated under environmentally relevant conditions using a mixture of PFAS differing in chain length and functional group. Both materials display a clear selectivity toward long-chain PFAS, with UiO-68-SSeS showing particularly high removal efficiency for perfluoroundecanoic acid (PFUnDA). These results demonstrate that rational linker design represents an effective approach to modulate the adsorption behavior of UiO-type MOFs, opening future perspectives for functional materials in water remediation.
The permeability-selectivity trade-off fundamentally constrains polymeric membranes, rooted in the dichotomy between chain flexibility and precise molecular sieving. The emerging concept of rubbery organic frameworks (ROFs) aims to bridge this gap, yet its reliance on reversible covalent chemistry inherently compromises structural stability. Here, we introduce an irreversible-chemistry paradigm by programming β-ketoenamine "irreversible knots" into flexible polydimethylsiloxane (PDMS) networks via enol-keto tautomerization. This approach synergistically co-programs crosslinking density and chain rigidity, yielding a stabilized and optimized microstructure. The resulting membrane transcends the classic trade-off, delivering a record-high flux of 5.4 kg m-2 h-1 for ethanol/water separation-three times higher than conventional PDMS-while maintaining a separation factor of 9.2. The "rigidity-programming" strategy demonstrates remarkable versatility, achieving top-tier performance across diverse separations spanning representative organic/water and gas-pair systems. Beyond performance, the membranes exhibit scalable fabrication, robust anti-swelling stability, and long-term operational durability, highlighting their practical potential for industrial deployment. This work establishes irreversible chemistry as a general paradigm for polymer network design, providing a robust platform to overcome traditional limitations from molecular separation to flexible functional materials.
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and remains difficult to treat because of diffuse invasion, immunosuppression, metabolic adaptability, and therapy resistance. This review evaluates how gut microbiota and microbiota-associated neuroinflammatory signaling may contribute to GBM biology and therapeutic response. We synthesized mechanistic, preclinical, translational, and emerging clinical evidence on microbiota-neuroinflammation interactions in GBM. The review focused on gut-brain axis pathways, microbial metabolites, blood-brain barrier (BBB) regulation, glial and myeloid immune activity, tumor-associated microbial signatures, microbial peptide-HLA presentation, and microbiome-informed biomarker or therapeutic strategies. Current evidence suggests that microbiota-related signals may influence GBM through systemic immune modulation, short-chain fatty acids, tryptophan-derived metabolites, polyamines, BBB effects, and altered microglial and tumor-associated myeloid cell function. Polyamine metabolism may sustain myeloid-cell-mediated immunosuppression in the acidic GBM tumor microenvironment, whereas microglial GLUT5-dependent fructose metabolism may limit inflammatory antigen presentation and adaptive antitumor immunity. Sequencing-based studies have reported bacterial and fungal nucleic acid signatures in brain tumor specimens, but these findings require careful interpretation because of low biomass, contamination risk, and methodological variability. Preclinical models further indicate that microbiome modulation can alter inflammatory tone, tumor growth, immune-cell infiltration, and response to immune checkpoint blockade. Microbiota-regulated neuroinflammation is a biologically plausible contributor to GBM progression, immune suppression, and treatment resistance. However, most evidence remains preclinical or early translational. Well-controlled, spatially resolved, multi-omic studies are required before microbiome-based biomarkers or interventions can be clinically implemented for patient stratification and future precision clinical neuro-oncology applications.
Left atrial (LA) dysfunction is a key preclinical phenotype of heart failure (HF), closely linked to HF progression, yet its molecular mechanisms remain unclear. Energy metabolic abnormalities may critically influence early LA dysfunction. This study aimed to explore the metabolic mechanisms underlying early LA dysfunction and develop a predictive model using metabolomics. We enrolled 315 participants, classified into early LA dysfunction and healthy control groups based on LA reservoir strain assessed via cardiovascular magnetic resonance (CMR). Targeted metabolomics was applied to detect plasma metabolites, and machine learning methods were used to construct predictive models. In addition, metabolic pathway and mediation analyses were also performed. A total of 11 metabolites were significantly altered in early LA dysfunction, including elevated short-chain acylcarnitines (C4OH, C5:1) and proline, and decreased linoleic acid. C4OH and C5:1 correlated positively, while linoleic acid negatively correlated with LA reservoir strain. These metabolites distinguished early LA dysfunction from controls effectively (AUC=0.716; 95% CI: 0.616-0.817). Mediation analysis indicated that C5:1 and C5OH exacerbated LA dysfunction partly via obesity (BMI). Energy metabolic-mechanical function uncoupling may underlie early LA dysfunction. C4OH, C5:1, linoleic acid, and proline represent potential biomarkers and candidate metabolic pathways for future therapeutic investigation for early HF detection and intervention. ChiCTR2200057991; Date of registration: 2022-03-25. URL: http://www.chictr.org.cn/showproj.aspx?proj=162316.
Nuclear medicine (NM) educators face a pivotal time of rapid scientific innovation and expansion of theranostic possibilities, rising volumes, staffing shortages, and a call for more high-quality training. In the midst of this expansion, AI technologies have disrupted nearly every aspect of society, including education. Although data on higher-level educational outcomes and patient-specific outcomes are limited, the rapid acceleration and sophistication of AI capabilities is undeniable and ubiquitous, causing many educators to express feelings of uncertainty, incompetence, distrust, and fear. Current literature on AI interventions in health education is limited, often favoring general introductory discussions over the practical application of foundational learning theory and ethical frameworks. In this 3-part article series, we began in part 1 with a foundation of traditional learning theories and ethical principles related to AI use in NM education. This article focuses on the practical application and integration of those foundational principles in the NM educator workflow. Beginning with an educator-focused theoretical framework grounded in transformative and experiential learning theories, readers are encouraged to practically engage with the activities in the article to experience the benefits and failures of AI use in education. Effective AI techniques, including prompt-engineering elements, chain-of-thought prompting, retrieval-augmented generation, custom AI tool development, multimedia content creation, and vibe coding, are introduced with practical activities. Readers should experience the activities directly and reflect on the application and integration in their own educational practice. AI-enabled NM educators who model theory-informed, ethical, and grounded AI use encourage learners to do the same, building interconnected networks of healthy human-AI interactions. These educational activities are naturally scalable and efficient, but with grounded, thoughtful approaches, they can also be equitable, accurate, and personalized. Meeting the rapid dynamics of NM practice requires a rapidly evolving and scalable educational system powered by AI technologies.
Rhabdomyolysis is characterized by skeletal muscle breakdown resulting in the release of intracellular contents into the circulation. Although trauma, medications, and metabolic disorders are common causes, viral infections are increasingly recognized as potential triggers. A 26-year-old previously healthy male presented with a 2-day history of abdominal pain, diarrhea, vomiting, bilateral thigh pain, and dark urine. Laboratory evaluation demonstrated severe rhabdomyolysis with a peak creatine phosphokinase (CK) level of 25,036 U/L, elevated aminotransferases, and preserved renal function. A stool gastrointestinal multiplex polymerase chain reaction (PCR) panel was positive for adenovirus and did not identify other enteric pathogens. Alternative etiologies, including significant recent exertion, medication-related muscle injury, toxin exposure, autoimmune myopathy, and inherited metabolic disorders, were considered but were not supported by the clinical history or disease course. The patient was treated with early intravenous isotonic fluid 1L every 6 hours and experienced progressive biochemical and clinical improvement without developing acute kidney injury. Adenovirus-associated rhabdomyolysis is an uncommon but increasingly recognized clinical entity in adults. The pathogenesis may involve direct viral muscle injury, immune-mediated inflammation, and contributory factors such as dehydration associated with gastrointestinal illness. Although adenovirus was considered the most likely precipitating factor in this case, a definitive causal relationship cannot be established. This case highlights probable adenovirus-associated rhabdomyolysis in an immunocompetent young adult presenting predominantly with gastrointestinal symptoms and preserved renal function despite marked creatine kinase elevation. Early recognition, careful evaluation of alternative etiologies, and prompt supportive management are important for preventing complications and achieving favorable outcomes.
Passive radiative cooling offers a sustainable pathway for thermal management by minimizing solar absorption while maximizing mid-infrared (MIR) emission through the atmospheric transparency window. However, parasitic heat gain substantially compromises its net cooling efficiency. Here, we report a reversible xanthation-mediated strategy to fabricate hierarchical SiO2@cellulose nanofiber aerogels that synergistically integrate broadband solar reflectivity, high MIR emissivity, and low thermal conductivity. The xanthation chemistry enables uniform, in situ anchoring of ∼300 nm SiO2 nanospheres along nanofibers, creating a distinctive 'pearl-necklace' morphology, while directional ice-templating further constructs lamellar hierarchical porous networks that suppress nonradiative heat transfer. The optimized aerogel exhibits an average solar reflectance of 95.6%, a MIR emissivity of 95.3% within the 8-13 µm atmospheric window, and an ultralow thermal conductivity of 0.028 W m-1 K-1. Under 1000 W m-2 solar irradiance, it achieves a time-averaged subambient cooling of 3.7°C and a net temperature reduction of 24.9°C compared to polystyrene foam, while extending refrigeration thermal cycling by 47.3%. This work provides a scalable material design framework for monolithic integration of optical selectivity and thermal insulation, offering a promising sustainable solution for energy-efficient buildings, cold-chain logistics, and next-generation thermal management systems.
Individuals with autosomal dominant frontotemporal dementia (FTD) exhibit considerable variability in disease onset and progression. Both modifiable and non-modifiable factors-such as sex, educational attainment or geographic region of residence-may contribute to this heterogeneity, potentially through their influence on cognitive reserve. The aim of the present study was to investigate the role of cognitive reserve modulators within the Genetic Frontotemporal dementia Initiative (GENFI) cohort. To this end, we used functional MRI (i.e. spatial chronnectome measures) and neurodegenerative markers (i.e. plasma neurofilament light chains levels) to determine disease stage using a Discriminative Event-Based Model (DEBM). We then examined how potential modulators influence the relationship between disease stage and cognitive performance. We analysed a total of 711 participants, including 106 patients with genetic FTD, 325 presymptomatic mutation carriers and 280 non-carriers healthy controls. Female participants showed a weaker association between disease stage and cognitive performance compared to males (P < 0.001), with difference becoming progressively more pronounced across symptomatic stages. Educational attainment exhibited a similar effect: individuals with higher education demonstrated an attenuated association compared to those with secondary or primary schooling (P < 0.001), with differences already detectable at prodromal disease stages. The effect of geographical region of residence was associated with education levels, but appeared to have an indirect and less strong influence. In summary, sex and educational attainment significantly affect the development and maintenance of cognitive reserve in individuals with genetic FTD. These findings underscore the importance of identifying disease-modifying interventions since the presymptomatic stages of the disease.
Klebsiella pneumoniae (K. pneumoniae ​​​​​) is a Gram-negative, encapsulated opportunistic pathogen causing pneumonia, urinary tract infections, bloodstream infections, and ventilator-associated pneumonia. Carbapenem resistance has made colistin a last-resort antibiotic for multidrug-resistant Gram-negative infections, but increased colistin use has driven resistance emergence. Resistance occurs through chromosomal mutations (mgrB, phoPQ, pmrAB) causing lipid A modification that reduces colistin binding, and plasmid-mediated mcr genes (especially mcr-1) encoding phosphoethanolamine transferase that spread horizontally across strains and species, making it a critical public health concern. Broth microdilution is the reference standard for susceptibility testing, while disk diffusion is unreliable. Molecular methods (polymerase chain reaction (PCR), sequencing) detect resistance genes and distinguish chromosomal versus plasmid-mediated mechanisms, providing comprehensive characterization for surveillance and outbreak investigation. Colistin-resistant K. pneumoniae is predominantly healthcare-associated, linked to ICU admission, prolonged hospitalization, broad-spectrum antibiotic exposure (carbapenems, colistin), and invasive devices (central venous catheters, urinary catheters, ventilators). Infections cause delayed effective therapy, prolonged hospital stay, increased complications, and higher mortality, particularly in critically ill patients with bloodstream infections or sepsis. India faces a high burden of carbapenem- and colistin-resistant isolates in tertiary care hospitals, yet molecular characterization data from regional hospitals remain limited. Rapid molecular diagnostics detecting mcr genes enable earlier appropriate therapy. Antimicrobial stewardship combined with infection control measures (contact precautions, hand hygiene, active surveillance, environmental cleaning) is essential to preserve colistin effectiveness and limit resistance spread, maintaining it as a last-line therapeutic option.
Although ERF transcription factors (TFs) play critical roles in abiotic stress tolerance, the molecular mechanisms underlying this role remain incompletely understood. This study identified BpERF1A in birch (Betula platyphylla) as a drought-responsive TF through co-expression regulatory network analysis. Expression of BpERF1A was stalwartly induced by drought stress, and drought treatment markedly boosted its promoter activity. Functional analyses demonstrated that overexpression of BpERF1A markedly improved drought tolerance compared with wild-type (WT) birch, whereas its repression increased drought sensitivity. Overexpression lines also exhibited higher antioxidant enzyme activities and proline content relative to WT. Chromatin immunoprecipitation-polymerase chain reaction, yeast one-hybrid and dual-luciferase (dual-LUC) assays confirmed that BpERF1A directly binds to G-box elements in the promoters of BpDHN (dehydrin) and BpAOS (allene oxide synthase), activating their transcription. Furthermore, overexpression of BpDHN/BpAOS enhanced drought tolerance and promoted reactive oxygen species (ROS) scavenging in transgenic plants. Protein-protein interaction analysis using bimolecular fluorescence complementation revealed that BpERF1A interacts with BpRAV1 to form a heterodimer, which further enhances BpERF1A binding to the BpDHN promoter and its transcriptional activation. Collectively, these findings establish a central role for the BpERF1A regulatory module in drought acclimation and highlight its synergistic interaction with BpRAV1, providing an effective strategy to enhance drought tolerance through improved ROS scavenging capacity.
Oxidative balance within follicular fluid (FF) plays an important role in oocyte competence and female fertility. However, most previous studies have focused on isolated oxidative biomarkers rather than on the coordinated organization of the follicular redox system. This study aimed to identify system-level oxidative phenotypes within FF and evaluate their associations with infertility-related clinical and metabolic factors. Seventy-seven women undergoing IVF treatment were included. Nineteen oxidative and antioxidative biomarkers were measured in FF collected separately from both ovaries. Bayesian multivariable regression with Markov chain Monte Carlo inference was combined with directional indicator analysis and unsupervised taxonomic clustering to identify latent oxidative phenotypes. Two structurally distinct and antagonistically organized oxidative phenotypes were identified within FF. Phenotype 1 comprised biomarkers representing the primary antioxidant defense system, whereas Phenotype 2 included enzymes involved predominantly in secondary detoxification pathways. Idiopathic infertility and BMI demonstrated significant and opposite directional effects across the two phenotypes. Specifically, increasing BMI and idiopathic infertility were associated with decreased activity of biomarkers belonging to Phenotype 1 and increased activity of biomarkers assigned to Phenotype 2 (p = 0.0177 and p = 0.0097, respectively). The follicular redox environment demonstrates a polarized and system-level biochemical architecture rather than uniform oxidative alterations. BMI and idiopathic infertility appear to selectively reorganize oxidative pathways within FF through opposite effects on two antagonistically structured phenotypes. These findings suggest a shared pathophysiological mechanism reorganizing the follicular antioxidant network in both conditions and challenge the single-biomarker paradigm in reproductive oxidative stress research.