Lithium metal batteries (LMBs) employing LiNi0.5Mn1.5O4 (LNMO) cathodes (5 V-class, vs Li+/Li) exhibit significant potential for next-generation energy storage owing to their high theoretical energy density and high-voltage capability. However, the practical development of LNMO/Li batteries is severely constrained by the incompatibility of carbonate-based electrolytes with highly reactive cathodes and anodes. To solve this, we propose a novel electrode-electrolyte interfacial engineering strategy: a dry electrode fabrication process is implemented, in which vapor-grown carbon fibers (VGCFs) are coated with polytetrafluoroethylene (PTFE) to passivate carbon active sites, thereby effectively mitigating electrolyte oxidation at high voltages. Simultaneously, lithium nonafluorobutanesulfonate (LNBS) and succinonitrile (SN) are incorporated as functional additives into the cathode. Mild heating during electrode fabrication melts these additives, enhancing the flexibility and mechanical integrity of the electrode. These additives partially dissolve during cell operation. LNBS contains SO3- polar groups that facilitate the dissociation of lithium salt ion pairs. Its electronegativity anchors transition metal ions onto the LNMO cathode surface, forming a Ni-S-containing adsorption layer that suppresses their migration into the electrolyte. Meanwhile, lithium difluoro(oxalato)borate (LiODFB) preferentially decomposes at the cathode interface, cooperatively forming a protective bilayer (an outer inorganic-rich layer and an inner Ni-S-containing absorption layer). At the anode, Li-SN (formed via coordination between SN and Li+) decomposes to generate an inorganic-rich solid electrolyte interphase (SEI), stabilizing lithium plating/stripping. These synergistic modifications enable LNMO/Li batteries with high-loading cathodes (20 mg cm-2) to achieve 88.6% capacity retention after 400 cycles at 0.5 C, with an average Coulombic efficiency of 99.44%. Moreover, when charged to 4.85 V, the cell maintains an open-circuit voltage above 4.68 V for over 1400 h, demonstrating exceptional cycling and storage stability with conventional carbonate-based electrolytes.
The pursuit of high-performance electromagnetic wave absorbers has directed significant attention to single-atom materials. Among these, transition metal single-atom nitrogen doped carbon materials (M-N-C) exhibit exceptional performance, primarily due to their tunable and unique electronic environments. The macroscopic performance of these materials in absorbing electromagnetic waves cannot be attributed to any solitary factor. Rather, it arises from the collective contribution and concerted interaction of various structural features at the micro level. In particular, understanding how the intrinsic properties of the metal centre M, especially the filling state of its d-orbitals and its electronegativity, determine the final macroscopic absorption performance is essential for the rational design of M-N-C absorbers. In this study, two-dimensional (2D) MOFs (Zn(M) ZIF-L) were exfoliated using the molten salt method to obtain M-N-C materials doped with single atoms of three different metals: Fe, Co and Cu. Using a molten salt method, MOFs are effectively exfoliated, yielding ultra-thin 2D nanosheets. This structural transformation markedly expands the specific surface area, which in turn promotes the attenuation and multiple reflection of electromagnetic waves. A systematic comparison of the regulatory effects of Fe, Co, and Cu single atoms on the surface electron localization distribution and polarization capacity reveals that Cu-NC exhibits the weakest dipole and interfacial polarization due to its fully occupied d-orbitals (3d10); Fe-NC possesses strong dipole polarization and partially unfilled d-orbitals (3d6), but its defect density and specific surface area are lower than those of Co-NC; whereas Co-NC, owing to its high dipole/interfacial polarization, the highest defect polarization, and richer multiple scattering, the material exhibits an optimal reflection loss of -64.538 dB at 15.12 GHz with a matched thickness of 2.42 mm. Moreover, an effective absorption bandwidth of 10.92 GHz (7.08-18 GHz) is achieved within the thickness range of 1.0 to 4.0 mm, showcasing its outstanding wave-attenuation capabilities. This work provides a deep understanding of the structure-property relationship from the atomic d-orbital level to macroscopic wave absorption performance, offering valuable guidance for the rational design of high-efficiency M-N-C-based electromagnetic wave absorbers.
Technological innovation is rapidly transforming surgical care, yet disparities in access and adoption persist. This study introduces a flexible, population-based model designed to assess and potentially guide the equitable implementation of advanced technologies in visceral (gastrointestinal) surgery, ranging from laparoscopy and basic imaging up to robotic-assisted surgery and artificial intelligence. We conducted a survey among technologically experienced visceral surgeons to classify current and emerging technologies by perceived complexity and requirement. This classification was used to query a self-developed translation model, which was integrated with demographic, hospital, and geographic data from official German sources. The model quantifies technological maturity and accessibility by calculating travel-to-treat times from the population's residence to hospitals offering specific technologies. We applied the model to the entire German population and all 16 counties, enabling regional and national comparisons. Based on the survey results, we constructed a layered classification for grouping surgical technologies with two dimensions, S and D, for surgical procedures and available devices and increasing levels of complexity (1-3). The model identified substantial regional disparities in access to advanced technology-assisted visceral surgery across Germany. While basic technologies (S1-S2, D1-D2) were broadly accessible nationwide, higher-level technologies such as robotic surgery (S3) were concentrated in urban areas. However, some advanced diagnostics (D3) were also available in remote regions. The model effectively quantified these differences from the population's perspective and demonstrated its potential for objective, population-based assessment of technological translation and accessibility. Our model highlights persistent regional disparities in advanced technology adoption and demonstrates potential for guiding equitable implementation strategies. Its population-based, data-driven approach can be extended to other countries, healthcare settings, and technologies, supporting political decision-making and improved patient access.
Fungal-derived chitosan (FCS) has emerged as a sustainable alternative to animal-derived chitosan (ACS) for biomedical applications. In this study, FCS fibers were fabricated via wet spinning and systematically compared with ACS fibers. FCS fibers exhibited a smaller fiber diameter, slightly lower crystallinity, and higher elongation, while maintaining a comparable chemical structure and thermal stability to ACS fibers. FCS fibers were subsequently twisted into yarns and functionalized with copper ions (Cu2 +) to prepare antibacterial sutures (Cu@FCS). Cu2+ loading onto FCS yarns increased with copper solution concentration, reaching 9.32 ± 4.01‰ (Cu-L@FCS), 30.83 ± 3.43‰ (Cu-M@FCS), and 126.25 ± 21.11‰ (Cu-H@FCS). Importantly, both Cu-L@FCS and Cu-M@FCS exhibited excellent cytocompatibility and hemocompatibility, whereas Cu-H@FCS showed cytotoxicity. Both Cu-L@FCS and Cu-M@FCS demonstrated potent antibacterial activity against S. aureus and E. coli. These groups also significantly enhanced L929 cell migration, achieving wound closure rates of 95.17 ± 2.78% and 96.97 ± 1.93% at 24 h. In vivo, Cu-M@FCS sutures effectively reduced inflammatory cell infiltration and promoted the healing of infected wounds. Collectively, Cu@FCS sutures combine sustainability, robust antibacterial activity, and enhanced wound-healing performance, underscoring their considerable promise for clinical translation in biomedical applications.
Sepsis remains a major clinical challenge characterized by immune dysregulation and coagulopathy. Ursodeoxycholic acid (UDCA) has been suggested to confer benefit in sepsis, but its mechanism remains unclear. This study explored whether UDCA modulates platelet function during sepsis via triggering receptor expressed on myeloid cells 2 (TREM2), an immunoreceptor with an emerging role in platelet biology. We employed an integrated strategy combining a retrospective cohort of 6476 sepsis patients (MIMIC-IV) with exploratory causal mediation analysis, mechanistic studies in LPS-induced septic and TREM2-knockout mice, computational docking suggesting a potential interaction between UDCA and TREM2, and a prospective pilot study in 8 septic patients receiving UDCA. Retrospective analysis showed that UDCA was associated with reduced hospital mortality (total effect -0.2287, P < 0.001), with 69.8% of this association mediated by increased platelet counts (natural indirect effect -0.1597, P < 0.001). Mechanistically, LPS downregulated platelet TREM2 and increased Syk-PI3K-Akt phosphorylation, accompanied by platelet hyperactivation. UDCA was associated with increased TREM2 expression and attenuated downstream signaling, and these effects were attenuated or not observed in TREM2-knockout mice. In the pilot clinical study, UDCA increased platelet counts (from 161.6 ± 106.2 to 211.4 ± 100.1 × 109/L, P = 0.001) and selectively inhibited ADP-induced aggregation (from 49.23 ± 20.45% to 31.63 ± 26.28%, P = 0.001) without significantly altering global coagulation parameters. In conclusion, these findings suggest that UDCA may be associated with improved sepsis outcomes by modulating platelet homeostasis in a TREM2-associated manner, providing preliminary translational support for TREM2 as a potential target in sepsis-associated coagulopathy.
Bromate has been strictly regulated in drinking water (< 10 μg L-1), due to its potential carcinogenicity and its poor removal efficacy by conventional water treatment processes. Although low-pressure UV-based advanced reduction processes (ARPs) can degrade bromate, their real‑world application is hindered by low efficiency under aerobic conditions and high energy demand. Herein, we demonstrated that the far-UVC (UV222)/sulfite process achieved efficient bromate removal under aerobic conditions at a fluence-based degradation rate constant of (5.08 ± 0.32) × 10-2 cm2 mJ-1 in deionized water at pH 9.0, which is 103.46 times higher than that of the conventional UV254/sulfite process. The UV222/sulfite process also exhibited robust performance in removing bromate in real tap water and surface water. The enhancement in efficiency is primarily attributed to the generation of higher concentrations of reductive radicals in the UV222/sulfite process. Kinetic modeling revealed a pronounced contribution of sulfite radicals (SO3•-) and hydrated electron (eaq-) to bromate degradation under aerobic conditions, accounting for 53.17% and 43.52%, respectively. The degradation of bromate in the UV222/sulfite process was promoted by increasing pH and initial sulfite dosage, and by decreasing the initial bromate concentration, whereas carbonate, nitrate, and natural organic matter (NOM) exerted inhibitory effects. The UV222/sulfite process reduced the formation of chlorinated disinfection byproducts (DBPs) in the post-chlorination and lowered the total calculated toxicity of the treated water by 78.29%. The UV222/sulfite process is thus established as a practical and energy-efficient technology to achieve effective bromate control in water under aerobic conditions.
Autism is a heterogeneous neurodevelopmental condition arising from complex interactions between genetic susceptibility and environmental factors. Lithium, a naturally occurring element used therapeutically for bipolar disorder and present in food and drinking water, warrants careful evaluation because it readily crosses the placenta and modulates biological pathways critical for brain development. We conducted a structured literature review of PubMed, Embase, and Web of Science through February 20, 2026, and identified 72 human, animal, and in vitro studies examining lithium exposure in relation to autism or neurodevelopmental outcomes. Epidemiologic evidence remains limited, with few studies directly assessing prenatal exposure and insufficient evidence to establish environmental lithium exposure as a neurodevelopmental risk factor. Most human clinical studies reflect therapeutic contexts and demonstrate the mood-stabilizing effects of lithium, whereas human biomarker and experimental studies provide evidence for modulation of glycogen synthase kinase-3β (GSK3β) signaling and thyroid function. Experimental studies indicate that lithium can normalize disease-associated phenotypes in autism-relevant models, yet it also induces behavioral and neurological alterations in non-mutant control models, particularly following high-dose or prenatal exposure. Across evidence streams, convergent findings implicate phosphatidylinositol-calcium signaling, GSK3β-dependent pathways, glutamatergic synapse function, and thyroid hormone regulation, supporting the biological plausibility of lithium-related neurodevelopmental effects. Overall, lithium-associated neurodevelopmental effects appear dose-, context-, and timing-dependent. Knowledge gaps remain regarding environmentally relevant prenatal exposures and long-term neurodevelopmental outcomes, underscoring the need for rigorous epidemiologic and mechanistic studies incorporating refined exposure assessment, developmental timing, and genetic susceptibility.
This work aims to develop and validate a hybrid electromagnetic(EM)-ArUco tracking framework integrated into a laparoscopic ultrasound augmentation system, aiming to improve accuracy, stability, and robustness in intraoperative visualization. A novel hybrid tracking method was developed that combines continuous hardware-based EM tracking with accurate but intermittent computer vision-based ArUco marker tracking, utilizing dynamically computed correction matrices to optimize the real-time spatial alignment of ultrasound and laparoscopic images. Validation involved three experiments: image-based analysis measuring pixel error between projected and ground-truth needle tips, target registration error analysis quantifying the distance between an EM- tracked stylus tip and the inverse projection from the ultrasound, and an ex vivo tissue experiment to assess distortions in a simulated clinical environment. Hybrid tracking demonstrated a significant reduction in tracking error compared to EM tracking alone. Hybrid tracking reduced projection error from 116 ± 49 px to 49 ± 18 px and decreased registration error from 2.1 ± 0.9 mm to 1.1 ± 0.6 mm. Under the influence of externally applied distortion, hybrid tracking improved tracking accuracy by approximately 62.3%. The system also exhibited robustness to camera rotation and zoom changes during periodic ArUco marker detection. The hybrid tracking framework significantly improved accuracy, stability, and robustness compared to EM tracking. This integration has the potential to enhance intraoperative visualization, thereby contributing to safer and more effective minimally invasive surgeries.
Agarwood is a highly valued fragrant wood produced naturally in Aquilaria species as a defense response to wounding and subsequent microbial infection. However, its natural formation is rare and time-intensive, necessitating the development of reliable and sustainable induction strategies. In this study, functionally screened fungal isolates obtained from wild agarwood were inoculated in mature Aquilaria malaccensis (syn. A. agallocha Roxb.) trees as both single and combined treatments, followed by temporal tissue harvest and assessment. Morphological and biochemical analysis indicated effective degradation of lignocellulosic barriers, facilitating tissue colonization. Within 21 days, deposition of dark resin and elevated expression of sesquiterpenoid biosynthesis genes, as confirmed by RT-qPCR, revealed transcriptional activation of multiple cascades associated with agarwood formation. GC-MS analysis further validated the quality of the induced agarwood. At 90 days, total sesquiterpenoid levels exceeded those of wild agarwood, with higher amounts of quality marker compounds typically reported in premium agarwood. The present study suggests that fungus, both in single and mix has the potential to address long-standing limitations of existing artificial inducers and provide a bio-based eco-friendly solution for commercial agarwood production.
Uptake of the measles-mumps-rubella vaccine in Wales is high. However, sporadic measles cases still occur and there are large mumps outbreaks every few years. In this study, the long-term vaccine effectiveness (VE) of vaccines containing measles and mumps is assessed. A retrospective cohort of 822 116 individuals aged 1-30 years were followed up between 1 January 2007 and 31 December 2020. Welsh Demographic Service data were linked to vaccination status from the national vaccination register and primary care records. Outcomes were identified by linking to laboratory confirmations (measles and mumps) and notifications (mumps) data. Complications were sourced from hospital admissions and primary care data. Extended Cox regression was used to calculate hazard ratios. The adjusted VE (aVE) against confirmed measles after two doses remained high after 15 years 99.7% [95% confidence interval (CI) 99.2-99.9]. The aVE for confirmed mumps was lower, with decline over time: 93.6% (95% CI 90.2-95.8) in the first 5 years after vaccination with dose two and 49.9% (95% CI 34.4-61.8) after ≥15 years. A third dose of mumps vaccine temporarily increases protection (87.6%, 95% CI 71.7-94.6). The aVE estimates for mumps were lower when based on clinical suspicion. The VE was high against complications for both infections. The high, sustained VE for measles strengthens evidence that elimination remains possible and the high VE against mumps complications is encouraging. Evidence for the waning of mumps immunity may be important when deciding to implement a third dose in outbreak settings. With the increased use of data linkage, studies should be conducted to corroborate these findings.
Stereotactic radiotherapy on CyberKnife demands high precision in dosimetry due to the involvement of small-field treatments. This study addresses the geometric and dosimetric limitations of conventional phantom setups when using small-volume ionization chambers by designing and validating a 3D-printed polylactic acid (PLA) insert for the Sun Nuclear StereoPhan phantom, optimized for the PTW PinPoint 31022 chamber. The insert was designed to eliminate air gaps and misalignments, ensuring accurate and reproducible point-dose measurements. Radiological suitability was confirmed through CT imaging, with the PLA insert showing a mean Hounsfield Unit (HU) of 137 ± 10 compared to 119 ± 5 for PMMA, demonstrating equivalence. Dosimetric validation on Varian TrueBeam and Accuray CyberKnife systems showed clinically acceptable accuracy, with dose deviations ≤ 1.98% for TrueBeam VMAT/IMRT plans and ≤ 3.502 ± 1.23 for CyberKnife cones as small as 5 mm. In contrast, conventional Farmer chamber setup showed deviations as high as 5.08%. In retrospective CyberKnife patient-specific QA, 87.8% of PLA-PinPoint measurements were within ± 5% and 93.9% within ± 10% of TPS-calculated doses across 33 plans, with a mean absolute deviation of 3.55% with a minimum error of 0.4% and a maximum error of -16%, compared to 11.63% for the SNC125c chamber. These findings demonstrate the feasibility of a cost-effective 3D-printed insert as a promising alternative to conventional phantoms, particularly for small-field CyberKnife QA in resource-limited settings.
Accumulating evidence indicates that diabetes is associated with increased risk of several cancers. The strongest evidence has been reported for cancers of the breast, colorectum, endometrium, liver, pancreas, and gallbladder. However, distinguishing causal relationships from associations driven by shared risk factors such as obesity, aging, and lifestyle behaviors remains challenging. Several biological mechanisms have been proposed to explain these associations. Key pathways include the effects of insulin resistance and compensatory hyperinsulinemia on mitogenic signaling pathways, including PI3K/AKT/mTOR and MAPK, as well as the influence of adiposity, chronic inflammation, and altered metabolic substrates on tumor initiation and progression. Hyperglycemia may also contribute by promoting tumor metabolism and cellular proliferation, although its independent contribution remains debated. These mechanisms likely interact to create a protumorigenic metabolic environment in individuals with diabetes. Obesity, which frequently co-occurs with diabetes, further amplifies these risks through altered adipokine secretion and increased estrogen production, highlighting the interrelated contributions of metabolic and hormonal factors. The relationship between diabetes and cancer has important clinical implications. Diabetes has been associated with worse cancer prognosis and higher cancer-related mortality, highlighting the importance of integrated management strategies. The impact of antihyperglycemic therapy on cancer risk and progression has been extensively studied, and ongoing research continues to evaluate potential protective or tumor-modifying effects. In this article, we summarize the epidemiologic and pathophysiologic evidence describing the relationship between diabetes and cancer and discuss strategies for risk mitigation, screening, and management.
Worldwide metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease. Despite high global prevalence, MASLD is not yet recognized as a noncommunicable disease, although all of the criteria are fulfilled for such a classification. MASLD is strongly associated with type 2 diabetes, cardiovascular disease, chronic kidney disease, and certain extrahepatic cancers. At 65% and 37% the prevalence of MASLD is extremely high in adults and children with type 2 diabetes, respectively. The pathogenesis of MASLD is closely related to that of type 2 diabetes, and diabetes-associated hyperglycemia, hyperinsulinemia, and hyperlipidemia promote progression from simple steatosis to hepatic inflammation and fibrosis. Thus, MASLD is now considered a complication of diabetes. However, there is still a great deal of work to be done to implement screening for and treatment of MASLD in everyday clinical diabetes management. In this article, the major mechanisms involved in the pathogenesis of MASLD and type 2 diabetes are discussed. Furthermore, the heterogeneity in the pathophysiology of MASLD and clusters in MASLD that may be relevant for future stratification of MASLD-associated risk of diseases are addressed. Finally, because of their strong hepato-, cardio-, and nephroprotective effects this article provides support as to why sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor (co)agonists should be used as first-line pharmacotherapies in people with MASLD and type 2 diabetes.
Limitations in Activities of Daily Living represent a crucial risk factor for cognitive decline, while the role of caregiving models in this process remains unclearly elucidated. To examine the correlation between different caregiving models and cognitive decline of people aged 45 and above with Basic Activity of Daily Living (BADL)/Instrumental Activities of Daily Living (IADL) limitations. Data were derived from the China Health and Retirement Longitudinal Study database covering the period 2011-2020. Using multiple linear regression models and linear mixed effect models (LMM), the association between different nursing models and cognitive function trajectories was systematically evaluated, and subgroup analyses were conducted to test the robustness and heterogeneity of the results. Multiple regression analysis indicated that spousal care was negatively associated with Mini-Mental State Examination (MMES) scores (OR=0.68, 95% CI: 0.12-1.24, P=0.017), whereas care provided by children, other relatives, and hired caregivers notably improved MMSE scores (P<0.05), with hired care yielding the greatest improvement (OR=4.61, 95% CI: 2.08-7.14, P<0.001). The LMM further revealed that, compared to no care, all other care types were substantially related to the rate of change in MMSE scores over time. Subgroup analysis demonstrated pronounced interactions in sex and chronic disease subgroups (P for interaction <0.05). This work provides empirical evidence for optimizing long-term care services, highlighting the importance of integrating professional care support to delay cognitive decline among individuals aged 45 and older with BADL/IADL limitations.
Gunshot residue (GSR) is an airborne mixture of chemicals and particles released after firearm discharge. There is limited information on cardiopulmonary effects of GSR specifically in a health relevant size fraction. This study evaluates the acute cardiopulmonary effects of GSR (particles ≤2.5 µm; GSR PM2.5) and investigates the role of the receptor for advanced glycation end-products (RAGE) signaling cascade in the mediation of inflammation and oxidative stress using wild-type (WT) and RAGE knockout (RKO) mice. GSR PM2.5 collected during a law enforcement pistol training contained characteristic GSR markers (lead, copper, and 2,4- dinitrotoluene). Right ventricle measurements were lower in the GSR PM2.5 treated animals compared to the control indicating potential pulmonary vasodilation regardless of genotype. Lead content in the heart was significantly higher in the GSR PM2.5 exposed mice, indicating systemic circulation. Inflammatory markers (NF-κB, TNF-α, SOD-1 and 2) in the lungs of RKO animals were significantly lower compared to the WT groups. The cardiovascular effects, differential inflammatory expression, and influence of RAGE signaling pathway on the cardiorespiratory response to GSR PM2.5 highlight the need for further investigation of longer exposure durations, mechanistic influences, and a more extensive chemical characterization of GSR PM2.5 in toxicological assessments.
Solid tumors remain refractory to chimeric antigen receptor (CAR) T cell therapy largely because they fail to infiltrate the tumor bed. We show that in vitro expanded HER2 CAR-T cells are more than 80% CCR7+ cells that migrate vigorously to CCL19. An E1B-55 kDa-deleted oncolytic adenovirus expressing CCL19 retained full oncolytic potency, secreted bioactive CCL19 and tripled CAR-T migration. In NSG mice bearing SKOV3 ovarian tumors, two intratumoral oAd-CCL19 injections followed by intravenous HER2-CAR-T cells achieved most effective inhibition of tumor growth without significant toxicity, accompanied by increased intratumoral CAR-T cells. Thus, CCL19-armed oncolytic adenovirus safely converts ovarian tumors into chemokine-rich targets that recruit CAR-T cells, providing a readily translatable strategy for solid-tumor CAR-T therapy.
Microneedle arrays (MNAs) is a rapidly emerging technology with broad biomedical applications in drug delivery and biosensing. With sub-millimeter dimensions and periodicity, MNAs possess geometries nearly ideal for biomedical devices operating within the terahertz (THz) spectral window. Because chirality is crucial to the function of deposited drugs and surrounding tissues, realizing chiroptical resonances within MNAs could impart new capabilities to microneedle-based technologies. However, methodologies for fabricating chiral MNAs are largely unknown and their importance remains largerly unrecognized. Here, we present a pathway to arrays of chiral microneedles (ARCHIMs) that exhibit strong and predictable chiroptical resonances in the THz range. These chiroplasmonic microneedles were prepared by glancing angle deposition of two sequential gold layers. ARCHIMs with thin, non-centrosymmetric caps on each needle exhibit strong chiral plasmonic modes characterized by distinct THz circular dichroism (TCD) bands and polarization rotations as large as 5 degrees. To emulate chiral drugs and biologics, we coated the ARCHIMs with L- and D-cystine crystals. We found that chiral phonons in the biocrystals resonate with chiral plasmons in the microneedles; their coupling induces handedness-dependent shifts in the TCD spectra. This photonic effect was quantitatively described using a modified temporal coupled mode theory that incorporates polarization-dependent resonator parameters. Our findings demonstrate that ARCHIMs provide an effective, tunable, and scalable platform for exploiting chiral light-matter interactions, opening new opportunities in TCD sensing, chiral diagnostics, chiral phonon detection and THz photonics.
The composite pollution of microplastics (MPs) and arsenic poses an increasingly severe threat to farmland ecosystems, but their joint toxic effects, especially the key role of MPs particle size, remain unclear. The combined effects of polyethylene microplastics (PE-MPs) with different particle sizes (0.5 μm, 5 μm, 50 μm, 500 μm) and arsenic on Ipomoea aquatica were revealed through hydroponic and pot experiments. It was found that the interaction between PE-MPs and arsenic exhibited a significant particle size-dependent transformation of synergistic-antagonistic effects. Specifically, small particle size PE-MPs (0.5 μm) were observed to act as a toxicity amplifier, with seed germination efficiency significantly inhibited (reduction >40%) even at low arsenic concentrations, and arsenic-induced inhibition of aboveground biomass was synergistically exacerbated (up to 35%) by intensifying oxidative stress (MDA content increased by up to 45.52%) and disrupting the photosynthetic system (lowest chlorophyll a content). In contrast, large particle size PE-MPs (500 μm) were found to play the role of a toxicity mitigator, particularly with antagonistic effects exhibited at higher arsenic concentrations by partially restoring belowground biomass (10-20% increase compared to single arsenic treatment) and alleviating oxidative damage. These findings demonstrate that PE-MPs particle size serves as a key switch regulating the direction and intensity of its combined toxicity with arsenic, which can provide a crucial theoretical basis for accurately assessing the ecological risks of MPs-metals/metalloids composite pollution.
Obesity and autoimmune diseases (AIDs) are each associated with elevated risk of cardiovascular and thromboembolic events. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular and metabolic benefits in patients with type 2 diabetes and obesity, but their effects in patients with obesity and comorbid AID remain uncertain. This study evaluated the association between GLP-1RA use and major adverse cardiovascular and thromboembolic event risk among adults with obesity and AID. This retrospective cohort study emulated a target trial using 2014 to 2024 electronic health record data from the OneFlorida+ network. Adults (aged ≥18 years) with AID and obesity eligible for antiobesity medication therapy were included. Exposure was defined as GLP-1RA use versus nonuse. Participants were matched using 1:1 time-dependent propensity scores. The primary outcomes were myocardial infarction, stroke or transient ischemic attack, pulmonary embolism, venous thromboembolism, and coronary revascularization. Secondary outcomes included hospitalization, emergency department visits, and all-cause mortality. We matched 13 204 GLP-1RA users and 13 204 nonusers (mean ± SD age, 54.7 ± 14.5 years; 73.4% women; mean body mass index, 37 kg/m2). GLP-1RA use was associated with lower hazard of stroke/transient ischemic attack (hazard ratio [HR], 0.87 [95% CI, 0.76-0.99]; P=0.039), pulmonary embolism (HR, 0.69 [95% CI, 0.56-0.86]; P=0.001), venous thromboembolism (HR, 0.83 [95% CI, 0.72-0.95]; P=0.007), emergency department visits (HR, 0.79 [95% CI, 0.75-0.83]; P<0.001), and mortality (HR, 0.56 [95% CI, 0.47-0.66]; P<0.001). Among adults with obesity and AID, GLP-1RA use was associated with reduced thromboembolic events, lower emergency department use, and decreased mortality, suggesting potential cardiovascular and survival benefits in this high-risk population.
CAR T cell therapy has demonstrated remarkable antitumor efficacy in hematologic malignancies, but its application in solid tumors remains challenging. This is primarily due to the suppressive tumor microenvironment, which impedes T cell infiltration and reduces their functionality. Compared with standard intravenous administration, localized delivery strategies offer significant promise for CAR T therapy in solid tumors. Nevertheless, most reported approaches rely on complex biomaterials and are mainly applied in immune-privileged tissues. Here, we developed an injectable, thermosensitive chitosan/β-glycerophosphate/gelatin (CS/G/GP) hydrogel for local delivery of GPC3-CAR T cells and the cytokine IL-15 to enhance therapeutic efficacy against solid tumors. This hydrogel not only supported in vitro survival and proliferation of CAR T cells but also limited passive diffusion of IL-15, thereby sustaining GPC3-CAR T cell activity, expansion, and cytotoxicity. In an in vivo NCG mouse model of hepatocellular carcinoma (HCC), hydrogel-mediated local injection markedly enhanced CAR T cell infiltration and antitumor activity within tumor tissues, without apparent systemic toxicity. Overall, our hydrogel platform offers a safe, feasible, and effective strategy for localized CAR T cell therapy, improving treatment efficacy in solid tumors.