Mango fruits undergo various biochemical changes and ripen rapidly after harvest. This study evaluated the effects of salicylic acid (SA) and hot water treatment (HWT) on the maintenance of postharvest quality of mango cv. Dashehari under ambient storage conditions. Physiologically mature fruits were subjected to different treatments, including SA 1 mM, SA 2 mM, HWT, HWT + SA 1 mM, HWT + SA 2 mM, and distilled water (control). Compared with untreated fruits, the combined treatments HWT + SA 1 mM and HWT + SA 2 mM significantly reduced weight loss, decay incidence, electrolyte leakage, reactive oxygen species accumulation, and activities of fruit softening enzymes, while better maintaining fruit firmness, soluble solids content, titratable acidity, and ascorbic acid during storage. The responses of these two combined treatments were statistically comparable for most quality attributes; however, fruits treated with HWT + SA 1 mM exhibited significantly lower malondialdehyde content after storage. These findings suggest that the integration of SA with HWT is an effective strategy for delaying ripening and preserving the postharvest biochemical quality of mango fruits under ambient conditions.
The blood-brain barrier (BBB) is a highly specialized interface that preserves neural homeostasis but severely limits the entry of therapeutic agents, posing a major challenge for central nervous system (CNS) drug development. While invasive approaches such as intracerebral injection and focused ultrasound can transiently bypass the barrier, their complexity and safety concerns restrict clinical applicability, particularly in chronic conditions. Non-invasive strategies that exploit endogenous transport mechanisms-carrier-mediated uptake, adsorptive-mediated transcytosis (AMT), and receptor-mediated transcytosis (RMT)-may offer a safer solution. Within this framework, brain shuttles have emerged as molecular vectors designed to cooperate with endothelial biology rather than disrupt it. These include antibodies, proteins, small molecules, and peptides, each with distinct advantages and limitations. Among them, peptides stand out for their versatility, manufacturability, and chemical tunability. Advances in solid-phase synthesis, non-natural modifications, and rational design have enabled peptides to achieve a balance between uptake efficiency and release beyond the endothelium. Their modular nature supports conjugation to diverse payloads, including small molecules, proteins, nucleic acids, and nanoparticles, while maintaining functional integrity. Peptide shuttles also offer broader receptor targeting and compatibility with multiple administration routes, positioning them as a cornerstone of future CNS delivery platforms. This chapter provides a mechanistic overview of the BBB, reviews invasive and non-invasive delivery strategies, and introduces the concept and evolution of brain shuttle peptides. It sets the stage for subsequent discussions on discovery methodologies, chemical optimization, validation models, and translational pathways, highlighting the promise of peptide-enabled systems to transform therapeutic access to the brain.
We systematically investigate PM6:Y12 bulk-heterojunction solar cells with donor fractions ranging from 1% to 45%, linking morphology, charge transport, and recombination to device performance. Complementary structural and spectroscopic methods reveal that a percolating PM6 network forms even at below 5% donor content, with lamellar stacking and vertical composition gradients that do not hinder the charge extraction. The reduction of the effective active layer conductivity toward low donor fractions obeys a three-dimensional percolation model, indicating that charge transport is governed by network topology rather without a pronounced percolation threshold. A transition from nongeminate Langevin recombination to a dispersive Smoluchowski-type loss occurs below 5% donor fraction. The latter regime is also nongeminate, i.e., pertains to recombination of the total charge carrier density. Correspondingly, we observe that the Langevin reduction in the higher donor fractions - mostly dominated by redissociation of electron-hole pairs after encounter - changes toward low donor fractions: in these cases, the nongeminate loss rate exceeds the prediction of the Langevin model. This regime coincides with increasing transport resistance due to topology-limited hole conduction, leading to reduced fill factors despite a high retained charge-generation efficiency. Our results demonstrate that strong donor dilution preserves photogeneration if a continuous donor network is maintained, and unveil how topology-controlled transport and non-Langevin recombination jointly define the performance limits of donor-diluted organic solar blends.
Ammonium (NH4+) and nitrite (NO2-) are key indicators of surface water quality, as their concentrations can change rapidly and even minor increases may threaten ecosystems and public health at trace levels. Although laboratory UV-vis spectrophotometry offers high accuracy, it is not suitable for on-site monitoring. Existing hand-held devices enable field testing but rarely integrate digitalization, online data storage, or geospatial mapping. In addition, portable colorimetric sensors often suffer from limited trace-level sensitivity and reduced accuracy over wide concentration ranges when single-regime calibration is used. In this study, we developed a simple, portable RGB colorimetric sensing device prototype combining indophenol-salicylate (NH4+) and Griess (NO2-) chemistries with smartphone-based readout using a compact TCS34725 sensor module. To address conventional calibration limitations, a machine learning-assisted dual-regime calibration (ML-assisted DRC) model based on segmented linear regression with a dummy-variable strategy was introduced. This approach preserves high low-level sensitivity while activating multivariate RGB corrections at higher concentrations, resolving the sensitivity-accuracy trade-off. Reliable quantification was achieved over an extended range, with LODs of 0.0221 mg·L-1 (NH4+) and 0.0096 mg·L-1 (NO2-), comparable to UV-vis results. The models showed excellent linearity (R2 ≥ 0.998), AOAC-consistent recoveries, good repeatability, and strong agreement with UV-vis measurements in real surface waters. Thus, the framework bridges low-cost portable sensing and laboratory-grade quantitative analysis for high-frequency field monitoring of inorganic nitrogen.
Liquid-liquid phase separation (LLPS) generates dynamic coacervate compartments whose fusion and dissolution behaviors are difficult to control without perturbing bulk conditions. Here, we introduce an interfacial polydopamine (pDA) coating strategy that programs the stability and morphological evolution of poly-L-lysine/ATP (pLys/ATP) coacervates. Dopamine oxidation with potassium permanganate (KMnO4) at the droplet interface yields a thin pDA shell that initially promotes droplet-droplet adhesion and rapid coalescence but subsequently suppresses further coarsening and preserves the size distribution over extended incubation. Microscopic analysis reveals that this coating primarily restructures the interface while retaining a fluid interior, enabling long-lived yet internally dynamic protocell-like assemblies. We further show that the pDA shell can be mechanically actuated by a small bifunctional diamine, which triggers fast centripetal contraction and expulsion of encapsulated contents, whereas a longer PEG-based crosslinker does not elicit such behavior. This chemically simple, two-input scheme establishes a generalizable route to arrest and reactivate LLPS-derived compartments, offering a versatile design element for systems chemistry, protocell models, and LLPS-guided delivery platforms.
Tumor hypoxia provides a unique biochemical cue for the development of microenvironment-responsive drug delivery systems with enhanced selectivity and therapeutic efficacy. Herein, we report a hypoxia-responsive supramolecular albumin conjugate (MAC) constructed by covalently grafting an azo-functionalized calixarene derivative (SAC4A) onto bovine serum albumin (BSA). In this design, SAC4A serves as both a supramolecular host for drug encapsulation and a reductive "molecular switch" that enables hypoxia-triggered activation, while albumin provides a biocompatible and tumor-affinitive transport scaffold. MAC preserves the strong host-guest recognition capability of SAC4A toward a wide range of chemotherapeutic agents and fluorescent probes, with binding constants in the 104-106 M-1 range. Rigorous global fitting and residual analysis confirm the reliability of the binding models. Under reductive conditions, the azo bonds in SAC4A are efficiently cleaved, leading to pronounced structural transformation, surface charge reversal, and controllable dissociation of guest molecules. Both chemical (sodium dithionite, SDT) and enzymatic (DT-diaphorase (NQO1)/NADPH) reduction experiments demonstrate that MAC exhibits high sensitivity and selectivity toward hypoxic environments. Using mitomycin C (MMC) as a model drug, we show that MAC enables precise hypoxia-triggered intracellular drug release, efficient lysosomal escape, and enhanced mitochondrial dysfunction. In vitro cytotoxicity assays reveal that MMC-MAC displays markedly amplified antitumor activity under hypoxic conditions, whereas free MMC shows no oxygen dependence, indicating that hypoxia selectivity is introduced by the carrier rather than the drug itself. In vivo studies further demonstrate that MMC-MAC achieves rapid and sustained tumor accumulation, significantly suppresses tumor growth, induces robust apoptosis, alleviates tumor hypoxia, and exhibits improved systemic biosafety compared with free MMC. This work establishes a supramolecular-biological hybrid strategy that integrates host-guest chemistry, albumin-based delivery, and hypoxia-responsive activation into a single platform, providing a modular and generalizable paradigm for constructing tumor microenvironment-selective nanomedicines with enhanced therapeutic index.
Chronic stress is a major risk factor for depression and disrupts myelin integrity in brain regions involved in emotional regulation. Although intermittent fasting (IF) improves metabolic and inflammatory states, its effects on stress-induced depression and demyelination remain unclear. Here, we investigated whether IF alleviates depression-like behaviors and myelin deficits in mice exposed to chronic restraint stress (CRS) and whether these effects involve modulation of the gut microbiota. Adult male C57BL/6 J mice underwent 14 days of CRS while maintained on either an ad libitum (AL) diet or an IF regimen. CRS induced robust depression-like phenotypes-characterized by increased immobility in the forced swimming test and reduced sucrose preference-without affecting locomotor activity, whereas IF significantly attenuated these behavioral abnormalities. Black-Gold II staining and myelin basic protein (MBP) immunofluorescence revealed marked demyelination in the corpus callosum, medial prefrontal cortex, and hippocampus of CRS mice, which was substantially reversed by IF. 16S rRNA sequencing demonstrated that IF reshaped gut microbial diversity and community composition under stress. Species-level analyses identified Prevotellamassilia timonensis and Muricoprocola aceti as positively associated with myelin integrity and behavioral improvement, whereas Anaeroplasma abactoclasticum showed negative associations. Functional pathway prediction further indicated that IF partially normalized stress-induced alterations in microbial metabolic functions. Collectively, these findings demonstrate that IF mitigates depression-like behaviors and preserves myelin integrity in CRS-exposed mice, potentially through gut microbiota-mediated mechanisms. IF may therefore represent a promising non-pharmacological strategy for alleviating stress-related neurobiological dysfunction.
Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration and chronic neuroinflammation. Increasing evidence suggests that microglial ferroptosis plays a critical role in the pathogenesis of PD. Troxerutin (TRX), a natural flavonoid derivative with potent antioxidant and anti-inflammatory activities, has shown neuroprotective potential; however, its effects on microglial ferroptosis and the underlying mechanisms in PD remain unclear. Here, we investigated the effects of TRX in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and MPP+-stimulated BV2 cells. TRX improves motor performance, preserves nigrostriatal dopaminergic neurons, and attenuates microglial activation and pro-inflammatory cytokine expression in vivo. In BV2 cells, TRX attenuated ferroptosis-related changes, reduced lipid reactive oxygen species accumulation, and restored GPX4 and SLC7A11 expression. Furthermore, treatment with erastin, a classical ferroptosis inducer, reactivates ferroptosis-related responses and reverses the anti-inflammatory effects of TRX, linking ferroptotic stress to microglial inflammatory activation. Mechanistically, the cellular thermal shift assay supported target engagement between TRX and NOX4. TRX enhances K48-linked polyubiquitination of NOX4 and promotes its proteasomal degradation, which restores Nrf2 nuclear accumulation and activates downstream antioxidant responses. These results reveal that TRX alleviates ferroptosis-related neuroinflammation by modulating the microglial NOX4/Nrf2 axis in PD.
Spatial transcriptomics technologies profile gene expression within its native spatial context, offering new insights into tissue organization and disease. However, accurate spatial domain identification remains challenging due to local oversmoothing, impaired topological fidelity, and insufficient modeling of global semantic structures. To address these challenges, we propose SpaVGMC, a unified representation learning framework that jointly models structural dependencies and transcriptional semantics. The framework integrates structured variational representation learning, structural information alignment, and semantic alignment, allowing the capture of probabilistic uncertainty, multiscale spatial dependencies, and global transcriptional organization. Specifically, SpaVGMC formulates representation learning as a structured variational inference process with context-aware message-passing. A structural information alignment mechanism preserves topological fidelity by aligning latent embeddings with the spatial graph via mutual information at both the edge and neighborhood levels. In addition, a semantic alignment mechanism organizes representations according to transcriptional similarity through distribution-aware contrastive learning without requiring data augmentation. By jointly modeling representations, structures, and semantics, SpaVGMC learns robust, discriminative, and biologically interpretable embeddings. Extensive experiments across diverse spatial transcriptomics data sets demonstrate that SpaVGMC consistently outperforms state-of-the-art methods in spatial domain identification, showing improved agreement with tissue structures and enhanced detection of fine-grained subdomains. Collectively, these results establish SpaVGMC as a robust and scalable framework for spatial omics analysis.
The swelling of the Li metal anode and its adverse impacts have barred lithium metal batteries (LMBs) from practical applications. Owing to insufficient recognition of the energy density-stress trade-off, no viable solution has emerged to halt their expansion or diminish their internal stress accumulation (SA) while preserving their exceptional energy density. We proposed principle-based criteria to guide the development of high-energy and low-swelling LMBs by defining the boundary parameters of strain-buffering techniques. Taking a typical space-adaptive buffering (SAB) layer as an example, we have materialized this criterion and verified its scientific validity and forward-looking nature, effectively reducing SA and mitigating the local stress concentration (SC). As a result, the Ah-level NCM9 (LiNixCoyMn1-x-yO2, x ≥ 0.9)||SAB-Cu pouch cell prototype with the high bare-cell energy densities of 465 Wh/kg and 1330 Wh/L exhibits the uniform stress distribution and low SC (extreme difference in local pressure<2 MPa), avoiding the failure of Li dendrite puncture. Furthermore, the Ah-level NCM811(Li1.2Ni0.8Co0.1Mn0.1O2)||SAB-Cu pouch cell demonstrates a perfect trade-off among energy densities (418 Wh/kg and 1061 Wh/L), cycle life (164 cycles with 77% capacity retention), SA (<2 MPa), and swelling ratio (3.6%), underscoring the practical feasibility of the SAB-AF-LMB.
Periarterial divestment has emerged as an artery-preserving alternative to formal arterial resection for borderline resectable and locally advanced pancreatic cancer. However, the available evidence remains limited. This study aimed to evaluate the perioperative and oncologic outcomes of periarterial divestment in pancreatic cancer. A systematic review was conducted using PubMed, Scopus, Web of Science, and the Cochrane Central Register to identify studies' data published up to March 2026. Continuous outcomes were pooled as means with 95% confidence intervals (CIs), and binary outcomes were pooled as proportions using random-effects models. Heterogeneity was assessed using the I2 statistic and the Cochrane Q test. Sensitivity analyses were performed using leave-one-out methods. All analyses were conducted in R version 4.4.2. Five retrospective observational studies comprising 474 patients were included, of whom 92.8% had locally advanced pancreatic cancer and 64.8% received neoadjuvant therapy. The pooled operative time was 333.0 minutes (95% CI: 232.6-433.4; I2 = 99%), estimated blood loss was 620.6 mL (95% CI: 292.4-948.7; I2 = 97%), and length of hospital stay was 12.4 days (95% CI: 9.1-15.6; I2 = 99%). The pooled incidence of intraabdominal infection, postoperative pancreatic fistula, postpancreatectomy hemorrhage, delayed gastric emptying, reoperation, major complications (Clavien-Dindo grade ≥ III), and 90-day mortality was 10.57%, 8.72%, 8.56%, 14.13%, 3.36%, 11.27%, and 4.18%, respectively. The pooled rates of venous resection, arterial resection, and R0 resection were 36.18%, 3.56%, and 43.33%, respectively. The pooled 1-year and 3-year disease-free survival rates were 50.42% and 17.77%, respectively, while the corresponding overall survival rates were 75.99% and 29.11%. Periarterial divestment has been applied in selected patients, with reported perioperative and oncologic outcomes across studies. However, the current evidence remains descriptive and does not allow comparative inference.
Darigabat is a selective γ-aminobutyric acid type A (GABA-A) receptor positive allosteric modulator targeting α2, α3, and α5 subunits, developed to preserve anxiolytic and anticonvulsant effects while reducing α1-mediated sedation and cognitive adverse events. Subtype-selective modulation represents a strategy to improve the safety of GABAergic therapies. A literature search in PubMed, Embase, CENTRAL, and ClinicalTrials.gov up to June 2025 identified 20 preclinical and clinical studies. Darigabat demonstrated dose-proportional pharmacokinetics, high brain penetration, and overall acceptable tolerability, with dose-dependent central nervous system adverse effects at higher exposures. Preclinical models showed anticonvulsant and anxiolytic activity. However, clinical trials reported heterogeneous and inconsistent efficacy across indications. Darigabat supports the feasibility of subtype-selective GABA-A modulation. Early-phase studies in healthy volunteers suggested improved acute tolerability compared with nonselective benzodiazepines. In contrast, repeated-dose studies in patients revealed dose-dependent central nervous system adverse effects, including somnolence, psychomotor slowing, and cognitive impairment, indicating that α1-sparing reduces but does not eliminate these effects. Current evidence does not support a clear therapeutic role in chronic central nervous system disorders. Future research should focus on exposure - response relationships, identification of responsive subgroups, and biomarker integration. The ability to retain efficacy with improved safety remains uncertain.
Beyond improving target delineation, functional imaging holds significant promise in identifying critical functional brain regions. It enables a more personalised approach to radiation therapy (RT) planning, where organs-at-risk can be spared more effectively, potentially preserving neurocognitive function and quality of life in patients with glioma. This systematic review aims to identify the role of functional imaging in preserving neurocognitive function in patients with glioma undergoing RT. A systematic review was conducted in December 2024 according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Searches were performed in Scopus, MEDLINE and EMBASE using medical subject headings and keywords related to glioma, functional imaging, cognition and RT. Only English-language publications were included. The Critical Appraisal Skills Programme (CASP) checklist was used to assess the validity and applicability of the studies included in this systematic review. Five studies published between 2019 and 2023 were included in the review. The studies included retrospective cohort studies (n = 2), a pilot study (n = 1), a cross-sectional study (n = 1) and a theoretical study (n = 1). Quality assessment using the CASP checklist indicated moderate methodological quality, with limitations including small sample sizes, predominantly retrospective designs and limited prospective validation of neurocognitive outcomes. Functional imaging was shown to reduce the dose to cognitive areas and potentially protect important cognitive functions. Functional imaging identifies critical cognitive regions in the brain and guides radiation dose to avoid these vulnerable regions while maintaining therapeutic efficacy. Integrating functional imaging into treatment planning allows for neuroprotective strategies in RT planning and potentially minimises the risk of cognitive impairment. This review sets the stage for future research to expand the benefit of functional imaging in glioma RT planning.
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Salt-bridge conservation has traditionally been evaluated at the primary sequence level, leaving the persistence of three-dimensional interaction sites across homologous families largely unexplored. In this study, we developed a systematic family-level structural framework to redefine salt-bridge conservation based on spatial interaction sites rather than residue identity by mapping salt bridges onto unified SCOP2-aligned domain coordinates. We classified these interactions into three categories: classically conserved (CLA), nonclassically conserved (NOCLA; i.e., charge compensation), and nonconserved. This spatial definition enabled the identification of charge-swapped interactions that are invisible to standard sequence alignment. Through a comprehensive analysis of 5,679 protein families, we demonstrated that charge compensation is a recurrent and evolutionarily preserved mode of spatial salt-bridge conservation across homologous families. NOCLA was not uniformly distributed but instead showed marked structural-context dependence, being preferentially enriched in alpha and beta proteins (a/b) and concentrated in a limited subset of folds, particularly protein kinase-like, PLP-dependent transferase-like, TIM beta/alpha-barrel, and globin-like folds. To assess functional relevance, we integrated variant-effect predictors, including AlphaMissense and ESM-1v. Our results revealed that spatially conserved salt bridges exhibited significantly higher mutational sensitivity and functional constraint than nonconserved sites (CLA > NOCLA > nonconserved). Notably, highly sensitive NOCLA positions were also the most structurally concentrated, arising predominantly from a restricted set of folds, especially protein kinase-like folds, in contrast to the broader distribution of CLA and the highly dispersed pattern of nonconserved sites. Furthermore, molecular dynamics (MD) simulations coupled with MDPath-based mutual-information network analysis demonstrated that disruption of a representative NOCLA site significantly reorganizes long-range communication pathways within conserved catalytic regions of kinase domains. These findings suggest that spatially conserved salt bridges serve not only as local electrostatic stabilizers but also as critical dynamic coupling nodes within protein structures. Together, this study provides a three-dimensional family-level paradigm for analyzing electrostatic interactions in protein evolution and offers new mechanistic insights for interpreting variant effects and guiding structure-based drug design.
Animals actively explore their surroundings to efficiently obtain resources, relying on the sensory modalities available to them. In South American weakly electric fish, self-generated electric organ discharges (EODs) create a short-range "sensory bubble" that, together with locomotion, supports exploration. This behavior relies on the coordinated modulation of spatial movement and electromotor activity, reflected in changes in EOD rate (EODr). However, how these components are engaged in natural contexts, and which conditions are sufficient to elicit exploration, remain poorly understood. Here, we examined how environmental and contextual factors modulate exploratory behavior in Gymnotus omarorum by combining a minimalistic laboratory assay with multi-day recordings in a seminatural arena. In laboratory tanks, freely moving fish showed minimal locomotor activity, which increased only when darkness and a novel electrosensory stimulus co-occurred, indicating strong context dependence and gating by chronobiological and motivational factors. By contrast, under seminatural conditions preserving natural light and temperature cycles, fish exhibited robust nocturnal rhythms in both locomotor activity and EODr. Chronobiological analysis revealed that the electrosensory rhythm consistently preceded the locomotor rhythm, with individual phase differences correlated across behaviors. These results show that exploration is a temporally organized behavior arising from coordinated modulation of sensory and motor systems. By linking electrosensory activity, locomotion, and circadian timing under ecologically relevant conditions, this study provides insight into how animals regulate sensory sampling and movement during exploration. Resumen Los animales exploran activamente su entorno para obtener recursos de manera eficiente, basándose en las modalidades sensoriales de las que disponen. En los peces eléctricos sudamericanos de descarga débil, las descargas del órgano eléctrico (DOEs) crean una "burbuja sensorial" de corto alcance que, junto con la locomoción, posibilita la exploración. Este comportamiento se apoya en la modulación coordinada del movimiento y la actividad electromotora, reflejada en cambios en la frecuencia de emisión de la DOE (fDOE). Sin embargo, aún se comprende poco cómo estos componentes se ponen en juego en contextos naturales y cuáles son las condiciones suficientes para desencadenar la exploración. En este estudio, examinamos cómo factores ambientales y contextuales modulan el comportamiento exploratorio en Gymnotus omarorum, combinando un ensayo de laboratorio minimalista con registros de varios días en una arena seminatural. En tanques de laboratorio, los peces en libre movimiento mostraron una actividad locomotora mínima, que aumentó únicamente cuando un estímulo electrosensorial novedoso fue presentado en horas de la noche, lo que indica una fuerte dependencia del contexto y un control ejercido por factores cronobiológicos y motivacionales. En contraste, bajo condiciones seminaturales que preservaron los ciclos naturales de luz y temperatura, los peces exhibieron ritmos nocturnos robustos tanto en la actividad locomotora como en la fDOE. El análisis cronobiológico reveló que el ritmo electrosensorial precedió consistentemente al ritmo locomotor, y que las diferencias individuales en la fase estuvieron correlacionadas entre ambos comportamientos. Estos resultados muestran que la exploración es un comportamiento organizado temporalmente que surge de la modulación coordinada de los sistemas electrosensiral y motor. Al vincular la actividad electrosensorial, la locomoción y la ritmicidad circadiana bajo condiciones ecológicamente relevantes, este estudio aporta información sobre cómo los animales regulan el muestreo sensorial y el movimiento durante la exploración.
To evaluate the level of insight into illness in patients with schizophrenia and its associations with demographic factors, clinical symptoms, executive functions, and selected metabolic parameters. This cross-sectional study included 60 outpatients diagnosed with schizophrenia according to DSMIV criteria. Participants were divided into two groups based on the median score of the Self-Appraisal of Illness Questionnaire (SAIQ): preserved insight (n=30) and impaired insight (n=30). Positive symptoms were assessed with the Positive Symptoms Rating Scale (PSRS), negative symptoms with the Brief Negative Symptom Assessment (BNSA), executive functions with the Wisconsin Card Sorting Test (WCST) and Wechsler-Bellevue Intelligence Scale-II (WB-II) subscales. Metabolic parameters included body mass index (BMI), systolic and diastolic blood pressure, and waist circumference. Statistical analysis was performed using t-tests, ANOVA, Pearson correlation, and multiple linear regression (p<0.05). Patients with impaired insight exhibited significantly higher positive (PSRS: 28.5±4.2 vs 18.3±3.1; p<0.001) and negative symptoms (BNSA: 35.2±5.6 vs 22.1±4.0; p<0.001), poorer executive performance (WCST total score: 45.6±8.9 vs 68.4±7.2; p<0.001), higher BMI (28.7±3.4 vs 24.5±2.8; p<0.01), and elevated blood pressure values. SAIQ total score negatively correlated with positive (r=-0.62; p<0.001) and negative symptoms (r=-0.58; p<0.001), illness duration (r=-0.45; p<0.01), and positively with years of education (r=0.48; p<0.01) and WCST score (r=0.52; p<0.001). Regression analysis showed that negative symptoms (β=-0.41; p<0.001) and executive dysfunction (β=-0.35; p<0.01) were the strongest independent predictors of poor insight (R²=0.62). Impaired insight in schizophrenia is strongly associated with greater psychopathological burden, neurocognitive deficits (especially executive dysfunction), and metabolic disturbances. These findings support the implementation of integrated therapeutic strategies targeting insight, cognition, and cardiometabolic health to improve long-term outcomes.
This paper examines the use of praise in the care of people living with dementia (PLWD) in the acute hospital. Perceptions of praise vary. 'Excessive' praise is typically classified as elderspeak, with attendant debates over whether this is patronising and/or infantilising. However, some sources suggest praise may serve useful structural functions in conversation, or should be used for encouragement of PLWD, reflecting the pervasive person-centred care ideology of supporting PLWD's existing abilities. Conversation analysis was used to examine 85 video and audio recordings of interactions involving PLWD and healthcare professionals in acute UK hospital wards. Findings suggest that although context sensitive, praise: 1) works as a supportive action to aid orientation to tasks and activities; and 2) has implications for the preservation of agency and face. Findings demonstrate the importance of sensitivity to individual interactional circumstances and have implications for healthcare practice, training and wider care of PLWD.
Systemic sclerosis (SSc) is a multisystem autoimmune disease frequently complicated by pre- and post-capillary pulmonary hypertension (PH). Within SSc, progressive diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are key contributors, often presenting as isolated postcapillary PH (Ipc-PH) or combined pre- and postcapillary PH (Cpc-PH). The ability to differentiate these hemodynamic phenotypes is critical for risk stratification, yet echocardiographic markers specific to each subtype in SSc-HFpEF are poorly defined. We investigated 147 adults with SSc-HFpEF with echocardiograms and right heart catheterization (RHC) assessments performed within one year. Patients were classified as Ipc-PH (n = 46) or Cpc-PH (n = 101) based on guideline-defined hemodynamic criteria. Echocardiographic parameters, including conventional measures, strain indices, and coupling metrics were analyzed. A random forest (RF) classifier was used to identify top echocardiographic predictors of Cpc-PH, and further assessed using multivariable logistic regression. Separate RF models and Cox regression analyses were used to determine echocardiographic predictors of mortality within each group. Survival was assessed using Kaplan-Meier analysis. Patients with Cpc-PH exhibited significantly greater right heart remodeling, higher pulmonary pressures, and impaired right ventricle (RV)-pulmonary artery (PA) coupling. The top echocardiographic predictors of Cpc-PH included reduced RV free wall strain (RVFWS), decreased RVFWS/PA systolic pressure (PASP) and fractional area change (FAC)/PASP ratios, elevated PASP, lower septal e' velocity, and higher systolic LV eccentricity index (LV EI). In adjusted Cox models, elevated LVEI (HR 1.39), increased RV internal diastolic diameter (HR 2.15), and reduced left and right atrial strain (HR 0.91 and 0.94, respectively) were independently associated with mortality in Cpc-PH. In Ipc-PH, mortality was linked to reduced FAC/PASP, lower left ventricular global longitudinal strain (LVGLS), increased LV mass index, elevated PASP, and lower RVFWS. In the present study, we demonstrate key echocardiographic differences between Ipc-PH and Cpc-PH within the SSc-HFpEF population, emphasizing the central role of right heart remodeling, RV-PA coupling, atrial and septal mechanics in phenotypic differentiation and prognostication. Strain-based parameters and RV-PA coupling indices offer incremental value for risk stratification and may guide more tailored therapeutic strategies in this heterogeneous population.
Pulmonary microcirculatory dysfunction is a hallmark of sepsis, contributing to hypoxemia, pulmonary edema, and multiple organ failure. Anisodamine hydrobromide (ADM), a natural alkaloid with anti-inflammatory and endothelial-protective properties, has been used clinically in China for septic shock. However, its effects on pulmonary microcirculatory dysfunction in septic shock remain unclear. A rat model of sepsis was established via cecal ligation and puncture (CLP). Rats were treated with low, medium, or high doses of ADM. Seven-day survival rates and arterial blood gas parameters were monitored. Pulmonary microvascular leakage was evaluated using Evans blue extravasation and FITC-dextran imaging. Histological analysis, immunofluorescence, and Western blotting were performed to assess leukocyte adhesion, inflammatory cell infiltration, endothelial junction proteins, basement membrane proteins, and matrix metalloproteinases. ADM treatment significantly improved 7-day survival and restored arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and pH in CLP rats. High-dose ADM markedly reduced Evans blue and FITC-dextran leakage, attenuated pulmonary edema, and preserved alveolar architecture. ADM inhibited leukocyte adhesion in pulmonary microvessels and decreased infiltration of MPO- and CD68-positive inflammatory cells. Mechanistically, ADM suppressed CLP-induced Caveolin-1 upregulation, restored the expression of VE-Cadherin, Occludin, and Claudin-5, and prevented degradation of Collagen IV and Laminin. Additionally, ADM significantly downregulated MMP-9 expression, while MMP-2 levels remained unchanged, suggesting a role in limiting junctional and basement membrane degradation. ADM protects against CLP-induced pulmonary microcirculation dysfunction in rats by attenuating inflammatory cell infiltration, preserving pulmonary endothelial junctions, and maintaining basement membrane integrity. These results provide mechanistic insight into ADM's therapeutic potential in sepsis-induced pulmonary microcirculation dysfunction and support its use for sepsis in clinic.