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VS-4718 enhances apoptosis induced by low-dose carfilzomib and overcomes carfilzomib resistance in PSMB5-mutated proteasome inhibitor resistant multiple myeloma

Abstract The introduction of proteasome inhibitors (PIs) into multiple myeloma (MM) treatment has substantially improved therapeutic options and survival rates. However, the development of resistance to PIs as well as serious side effects of PI treatment continue to justify the search for effective, less burdensome combination therapies. Thus, we investigated the therapeutic potential of VS-4718 (dual pPYK2- and pFAK-inhibitor) alone and in combination with the PI carfilzomib (carf) in parental human MM cell lines (pHMCLs) and PI triple-resistant HMCLs (rHMCLs). VS-4718 reduced the viability in a concentration dependent manner in all pHMCLs and the response was independent of PYK2 expression or activation. A more than additive impact of the combination therapy on survival, measured by annexin V-FITC/PI staining, was observed in 5/7 pHMCLs. Titration experiments showed that VS-4718 in combination with low and sublethal doses of carf had a specific anti-tumor effect on pHMCLs but hardly affected peripheral blood mononuclear cells. In rHMCLs, addition of VS-4718 to carf re-sensitized cells to carf and revealed a more than additive reduction in cell survival. These findings suggest that VS-4718 together with low doses of carf could be an effective and low-toxic combination in MM, including PI-resistant, relapsed/refractory MM.

The impact of chronic kidney disease on patient and caregiver quality of life: A qualitative study in Spain

Patients’ quality of life is a key consideration of chronic kidney disease care. Nonetheless, qualitative research on patients’ experience, quality of life, and frequent associated comorbidities remains limited. This study identifies aspects of the disease experience, healthcare journey, and caregiver experience contributing to quality of life for early-stage (stage 3 CKD) and advanced chronic kidney disease (stages 4–5) patients and their caregivers. In this cross-sectional, observational, multicenter study based on qualitative methodology, participants completed a general (Short Form-36) and disease-specific (Kidney Disease Quality of Life Short Form−36) quality of life assessment and semi-structured interviews. Quota and convenience sampling were used to enroll 36 patients selected by clinicians based on chronic kidney disease stage and the presence of key comorbidities (heart failure, hyperkalemia). Twelve caregivers were also invited to participate in patient interviews. All data were examined thematically. Three themes emerged: (1) Impact of chronic kidney disease on quality of life throughout the patient journey (physical, social, and emotional); (2) attitudes toward the disease (characterized by ‘acceptance’ or ‘powerlessness’); and (3) caregivers’ role and burden. Patients’ characteristics and caregiver support must be considered for designing medical interventions and improvement of patient-doctor communication. Family caregivers are pillars clinicians should rely on to raise awareness about chronic kidney disease’s relevance among patients and families.

Sensitive x-ray and extended near-infrared detection with doped perovskite single crystal

Conventional all-inorganic perovskite photodetectors typically exhibit photoresponse limited to the visible region (<800 nm). In this work, we demonstrate a broadband photodetection strategy by introducing Fe dopants into Cs2AgBiBr6 double perovskites, extending the spectral response to ∼1200 nm in the near-infrared (NIR) region. These states enable sub-bandgap photon absorption through transitions involving these defect-induced energy levels, thereby facilitating NIR detection. Furthermore, the Fe-doped Cs2AgBiBr6 (Fe:Cs2AgBiBr6) devices do not compromise the intrinsic X-ray detection performance of Cs2AgBiBr6 while enabling a pronounced enhancement in NIR photoresponse. This study provides an effective doping-driven approach to broaden the operational spectral range of all-inorganic perovskite photodetectors and highlights the potential of defect-state engineering for multifunctional optoelectronic applications.

Green nanotechnology: Adenanthera pavonina-derived silver nanoparticles with antibacterial and photocatalytic properties

How the characteristics of a virtual environment affects the perception of travel distance through it

Although simulated self-motion through virtual environments has been widely used to investigate perceptual odometry, the characteristics of the virtual environments used, and the reported results, have varied greatly. To investigate how the characteristics of a virtual environment affect the perception of travel distance, we systematically vary the characteristics of the environment through which observers are moved in order to explore the effect of (1) the structure of an environment including the presence and texture of a ground surface, (2) the naturalism and scale of an environment, (3) colour, and (4) the density of a starfield. In all four experiments, participants were visually moved forwards through a virtual environment and perceived travel distance was estimated by either (1) stopping at the location of a previously seen target (the Move-To-Target Task) or (2) adjusting the position of a target to indicate a previously travelled distance (the Adjust-Target Task). Data were analyzed in terms of gain (perceived travel distance/actual travel distance). Results show no significant differences that depended on the structure of an environment or on the presence or absence of a ground surface (Experiment 1), or on the naturalism of the environment (Experiment 2), or on whether the environment was in colour or in black and white (Experiment 3). However, there was a small effect of the texture of the ground surface and of the scale of the environment. In Experiment 4, we show that there may be a very low ceiling effect in the density of a starfield needed to accurately estimate travel distance. Together these experiments have implications for the design of real and virtual environments where perceived motion is important and will enable us to further predict our perception of moving through an environment.

Exciton-polariton lasing with polarization fixing reciprocal space resolved at room temperature

Exciton-polaritons are quasiparticles that are defined by the interaction between semiconductors and optical cavities. The ultra-low effective mass of polariton quasi-particles from its photonic component facilitates the polariton lasing processes at high temperature. The fixing of initial exciton polarization necessitates a method to achieve a stable polarized output. In this paper, we demonstrate the polarization-fixed polariton condensation lasing at room temperature, which is based on the anisotropy inherent in the gain media crystal structure. At the threshold (Pth = 25 kW cm−2), emission intensity exhibits nonlinear growth, and linewidth undergoes a sharp contraction. The dispersion curve of TE–TM polarization splitting was fitted by using a coupled Lorentz resonator model. Its validity was verified by adjusting the detuning amount to match experimental results. Moreover, the perpendicular emission directions of TE and TM polarization are indicated by reciprocal space imaging. The significance of first-order coherence of polariton lasing is explained qualitatively via the Michelson interferometer. Our results provide a feasible route for the development of polariton optoelectronic devices with tunable polarization degrees of freedom.

Land use induced variations in soil fertility and physicochemical properties across surface and subsurface layers

Pathogenicity of Purpureocillium lilacinum and Clonostachys rosea against fall armyworm (Spodoptera frugiperda) under laboratory conditions

Background Fall armyworm, Spodoptera frugiperda (J.E. Smith) threatens staple crops across Africa. Integrating entomopathogenic fungi into Integrated Pest Management (IPM) offers a sustainable alternative to sole reliance on insecticides. This study quantified the pathogenicity of Purpureocillium lilacinum and Clonostachys rosea against S. frugiperda under controlled conditions. Methods Second-fifth instar larvae and eggs were exposed to 1 × 10 7 , 1 × 10 8 , and 1 × 10 9 conidia mL -1 of each fungus; sterile water served as control. Mortality was recorded over 3–9 days after treatment (DAT); feeding reduction was measured gravimetrically. Larval mortality was analyzed with GLMs/GLMMs (binomial-probit); feeding reduction by ANOVA/Tukey; LD50 and LT50 were estimated from dose-response models. Results Larval mortality was significantly affected by concentration × time interaction and declined with advancing larval stage. Peak larval mortality was reached at a concentration of 1 × 10 9 conidia mL -1 at 9 DAT. Feeding consumption reduction was significantly affected by larval instar, EPF species, and instar × concentration. Feeding reduction reached 60−74% in early instars at the highest dose. Egg mortality was primarily concentration-dependent with maximum values (up to 82% and 88% for P. lilacinum and C. rosea , respectively) at the dose of 1 × 10 9 conidia mL -1 highest dose. Our findings supported the study hypothesis that efficacy of entomopathogenic fungi against S. frugiperda is primarily driven by interaction of spore concentration and exposure time across the host developmental stages, rather than the interaction of fungal species. The consistent susceptibility of early instars and the strong concentration-dependent responses highlight the functional potential of these native fungi as biologically relevant components of sustainable IPM strategies. Conclusions Native P. lilacinum and C. rosea display dose‑, stage‑, and time‑dependent pathogenicity and feeding suppression against S. frugiperda . These species are promising candidates for IPM; field validation and formulation optimization are the next steps.

Enhanced LIBS detection of atomic oxygen via two-photon LIF

Laser-induced breakdown spectroscopy (LIBS) is a versatile analytical technique with applications in several fields of science and technology. It requires minimal or no sample preparation and can provide information about the composition of the analyte, with limits of detection typically at the ppm level. There is growing interest in the scientific community in improving the sensitivity and specificity of LIBS. In this work, we explore the combination of LIBS with two-photon laser-induced fluorescence (TALIF) for the enhancement of atomic oxygen spectra signatures originating from a nanosecond laser-produced plasma on a solid target. The line intensity of the O I transition at 844.67 nm was enhanced up to 29.3 times by exciting an oxygen atomic resonance using a second UV nanosecond pulse at 225.59 nm, with a focused intensity of ∼2.4×107 W/cm2, produced with an optical parametric oscillator. The enhancement did not significantly increase the background, leading to a comparable increase in the signal-to-noise ratio. The dependence of the enhancement on the UV excitation wavelength and on the inter-pulse delay is presented. The demonstrated LIBS-TALIF combination permits the exploration of high-lying gaseous transitions not accessible with classical laser-induced fluorescence and unlocks the pathway to applications where increased sensitivity and specificity are imperative.

R3MV: a novel reliable system architecture for skin cancer classification using progressive heterogeneous multiblock model

Injury patterns and cumulative injury burden among U.S. competitive fencers: A survey

Background Fencing is a highly asymmetrical sport that combines both repetitive upper-extremity and lower-extremity actions. Although fencing related injuries have been described in clinical- and competition-based cohorts, population level data capturing both training and competition exposures and cumulative injury burden remains limited. Objective To characterize injury patterns, mechanisms, and anatomical distribution among adult competitive fencers and to examine associations between training related exposures and reported injury burden. Methods Adult competitive fencers registered with USA Fencing were invited to complete an anonymous web-based survey capturing demographics, training and competition exposures, and self-reported fencing related injuries. Injury burden was defined as experiencing three or more lifetime fencing-related injuries among injured respondents. Multivariable logistic regression was used to examine associations between training exposures and injury burden with continuous predictors modeled using restricted (natural) cubic splines to allow for non-linear relationships. Descriptive analyses, correlation analyses, and Poisson regression were performed as sensitivity analyses. Results Among 303 respondents, 270 (89.1%) reported at least one fencing related injury, accounting for 571 total injuries. Overuse injuries predominated and most frequently involved the knee, ankle and dominant upper extremity with gradual-onset, non-contact mechanisms accounting for the majority of the injuries. Upper-extremity injuries were significantly more likely to occur on the dominant side. In multivariable analyses, years of fencing experience demonstrated a significant non-linear association with higher injury burden, while weekly training volume showed a non-linear association that approached statistical significance. Age at starting fencing, competition frequency, and sex were not independently associated with injury burden. Sensitivity analyses using Poisson regression yielded qualitatively similar findings. Conclusions Among adult competitive fencers, higher injury burden is most strongly associated with cumulative training exposure, particularly years of fencing experience, with additional contribution from weekly training volume. Injury patterns are characterized by overuse and pronounced dominant-side upper-extremity involvement, consistent with the sport’s asymmetrical biomechanical demands. These findings underscore the importance of monitoring cumulative exposure and addressing asymmetrical loading to mitigate recurrent injury burden in fencing.

Transition-selective photoluminescence of InSb quantum dots on GaSb substrate

Transition-selective photoluminescence (TSPL) spectroscopy was applied to InSb quantum dots (QDs) grown on GaSb substrates to resolve the overlapping photoluminescence (PL) transitions that were indistinguishable in conventional measurements. TSPL is a frequency-domain measurement technique in which the excitation laser intensity is modulated. Based on the modulation frequency dependence of the PL intensity and phase, the measured PL lifetimes of the InSb QDs and GaSb were approximately 3 and 5 ns, respectively. The PL originating from the impurity bands in GaSb was successfully isolated from those emitted by band-to-band transitions and InSb QDs; these PL features were otherwise obscured by adjacent transitions. The selection of these transitions was attributed to detection-phase control that enabled selective suppression of unwanted transitions. These results demonstrate that TSPL is a powerful technique for extracting transition-specific information from semiconductor heterostructures.

Correction: Targeting cell surface GRP78-CD44v interaction suppresses cell migration in triple-negative breast cancer cells

Study on strength criterion of progressive failure of structural loess under hydraulic action and true triaxial test

The strength behavior of natural loess is governed by its inherent structure and is sensitive to humidity and stress paths, posing challenges for stability assessment in loess engineering. To address this, a three-dimensional strength criterion for structural loess is developed by introducing a shape change coefficient and a structural state parameter, effectively extending classical failure criteria to account for true triaxial stress effects. This criterion is integrated into the Mohr-Coulomb model and implemented in FLAC3D via a custom subroutine for numerical simulation. The model is validated against a series of true triaxial tests under various consolidation pressures (50-300kPa) and intermediate principal stress ratios (b = 0–1). Results show that the proposed criterion accurately captures the stress-strain response and strength evolution of loess, with simulation errors within 5% and strong correlation to experimental data. The study provides a practical theoretical tool for analyzing progressive failure in loess under hydraulic and mechanical actions, with direct relevance to slope, tunnel, and foundation engineering in loess regions.

Temperature negative self-feedback preventing thermal runaway in lead-free energy-storage ceramics

Lead-free multilayer ceramic capacitors (MLCC) have received unprecedented attention for energy storage in constantly lightweighted and miniaturized electronic and electrical systems. However, their popularized application is still bottlenecked by the thermal runaway issues of energy-storage ceramics because of the common nature of temperature positive self-feedback characteristics that are reflected by continuously increasing power loss with elevated temperatures. In this work, temperature negative self-feedback that prevents thermal runaway is realized in NaNbO3 modified 0.87BaTiO3-0.13Bi[Zn2/3(Nb0.85Ta0.15)1/3]O3 (NN0, NN0.05, NN0.10, NN0.15, NN0.20) lead-free energy-storage ceramics as a demonstration, based on a strategy of peak shifting and loss suppression. Negative self-feedback at weak and strong electric fields was attained by the temperature dependent power loss extracted from dielectric-temperature curves and polarization–electric field loops, respectively, in which NN0.05 is the optimal selection because of the largest negative self-feedback range from 25 to 150 °C and minimally declined energy-storage performance compared to the pristine NN0. Thermal field simulation of single ceramic layers indicates that NN0.05 achieves faster thermal stabilization with lower than NN0. Based on the Monte Carlo method, MLCC consisting of 20 ceramic layers with different defect levels were created, and evenly distributed temperature was confirmed for NN0.05 with prevented thermal runaway. General applicability and advantages of temperature negative self-feedback preventing thermal runaway in energy-storage ceramics were verified by three artificial types of MLCC. This work offers a solution to the critical thermal runaway issues of lead-free energy-storage ceramics, facilitating their wide application in MLCC toward lightweighted and miniaturized electronic and electrical systems.

Nature versus nurture: genetic background and media composition shape endothelial cell transcriptomes in vitro

Abstract Primary endothelial cells (e.g., HUVEC) are essential in basic research and drug development, yet contradictory or poorly reproducible experimental results are common in the literature. We investigated whether such discrepancies arise from differences in culture media or donor genetic backgrounds using Agilent microarray transcriptomic analysis of three donor-derived HUVEC lines cultured in four distinct media (regarding basic composition, serum- and growth factor content). Genome-wide cluster analysis of 13,823 expressed genes revealed that samples clustered primarily by medium. Of the 2215 genes showing differential expression, 1697 varied across media, while only 805 were affected by donor differences. Correlation and principal component analysis confirmed that media composition had a strong impact on gene expression. Functional analysis of nine key endothelial functions showed predominantly medium-dependent effects, particularly on mitosis, angiogenesis, inflammation, and adhesion. The pivotal role of media composition in shaping HUVEC transcriptome may underlie inconsistencies across studies.

Effects of music therapy in patients with diabetic retinopathy undergoing pan‑retinal photocoagulation

Objectives Pan-retinal photocoagulation is a common outpatient procedure for diabetic retinopathy that often causes procedural pain and anxiety. Nonpharmacologic interventions such as music therapy may provide relief but are underexplored in this population. This study aimed to evaluate the effectiveness of a three-phase music therapy intervention in reducing pain, anxiety, and physiological responses during pan-retinal photocoagulation, and to explore its potential as a supportive outpatient strategy. Methods Quasi-experimental study. Setting Ophthalmology Outpatient Department, The First Affiliated Hospital of Soochow University. Participants Participants were non-randomly allocated. This experimental study allocated participants to groups based on clinic visiting time. Patients attending on Tuesday and Wednesday mornings were assigned to the intervention group, while those attending on Tuesday afternoons formed the control group receiving usual care. This time-based allocation minimized cross-contamination and facilitated implementation in routine practice. 116 patients with diabetes were assigned to experimental or control groups, out of which 59 patients completed the intervention. Intervention The intervention consisted of listening to pre-recorded three-phase classical music combined with audiovisual education. The control group only received the audiovisual education. Outcome measures Primary outcome was pain, measured by the Visual Analog Scale, it was taken during treatment and 5 minutes after treatment; secondary outcomes included state anxiety (Spielberger State-Trait Anxiety Inventory), heart rate and blood pressure (Omron electronic sphygmomanometer). Theses measurements were taken 15 minutes before and 5 minutes after treatment. Post-treatment satisfaction was evaluated using a study-specific, self-developed questionnaire comprising six items rated on a 5-point Likert scale. Results Pain, anxiety, systolic blood pressure and diastolic blood pressure were lower in the intervention group compared with control group ( p  < 0.05). No significant differences in heart rate were observed between groups. There were none adverse events occurred during intervention. Satisfaction was high in both groups, the intervention group rated staff education content and service attitude higher ( p  < 0.05), with no other between-group differences, and music acceptability was favorable. Conclusion A three-phase music therapy intervention is a safe and effective approach for reducing procedural pain, anxiety, and blood pressure in patients undergoing PRP. These results support its integration as a nonpharmacologic option in outpatient ophthalmologic care. Trial registration number: ChiCTR2500106330 .

Large thermoelastic effect in <b> <i>α</i> ″ </b> martensite of TiZrNbSn

Highly reversible elastic deformation endows the associated thermoelastic effect with considerable potential for solid-state cooling. In this work, we report a large adiabatic temperature change (ΔTad) in a TiZrNbSn alloy with α″ martensite. To enhance ΔTad, a microstructure optimization strategy based on broadening single-variant martensite domains via compressive preloading is implemented. Unlike the stress-free, self-accommodated martensitic state, stress-induced detwinning promotes a single-variant state in which the [100] orientation aligns with the compression direction. In this state, the lattice deforms cooperatively under stress, leading to a significantly enhanced thermoelastic response. Consequently, ΔTad increases progressively with higher preloading stress, reaching a value three times greater at 800 MPa than that of the non-preloaded sample. However, excessive preloading activates dislocation slip, which degrades the thermoelastic response. The alloy also exhibits a wide operating temperature range of 295–475 K, achieving a ΔTad of 2.0 K at 475 K. This work provides insights into the microstructure–property relationship governing the thermoelastic effect in martensitic alloys.

Organophosphate pesticide DEDT promotes diabetic retinopathy progression via AMPK/Nrf2/HO-1 pathway

Interoception in adolescence: Evidence from multidomain self-report of bodily sensations and cardiac behavioral measures

Interoception, the sense of inner bodily signals, plays a key role in emotional regulation, cognition and mental health. While its relevance in adulthood has been extensively explored, less is known about how interoceptive  abilities develop during adolescence, a period characterised by significant physical and psychological changes. This study aimed to investigate different interoceptive dimensions in adolescents and adults to better understand the developmental profile of this sense. Fifty-four adolescents (aged 12–14) and 50 adults (aged 25–34) completed the Heartbeat Counting Task (HCT) to assess their actual ability to detect heartbeats, their confidence in this ability, and the confidence-accuracy correspondence, and a questionnaire on the tendency to focus on different bodily sensations. The study also examined where participants localised bodily sensations during the HCT. No clear group differences emerged in the accuracy during the HCT. Also, both age groups exhibited similar body localisation patterns, primarily focusing on the chest during heartbeat detection. However, adolescents showed significantly lower metacognitive awareness of their ability to perceive cardiac signals, and higher focus on interoceptive sensations, as reflected in their higher confidence ratings in the HCT and elevated scores on a questionnaire assessing the perceived frequency of internal bodily sensations. There were no significant correlations among the interoceptive measures in either group, suggesting that they may capture partially distinct aspects of interoceptive functioning and contributing to the ongoing debate on how interoceptive dimensions should be conceptualized and measured. Overall, these findings suggest that, while basic interoceptive detection may be established by early adolescence, the capacity to accurately reflect on these internal sensations continues to mature into adulthood, at least for what attains the cardiac domain. Also, the mismatch observed between adolescents’ heightened bodily focus and their limited metacognitive insight may partly help explain why adolescence is a period of increased vulnerability to mental health difficulties.