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The standard treatment modality for high grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of ovarian cancer, consists of surgery followed by chemotherapy, which is associated with major challenges including off-target effects and therapy resistance. Ferroptosis, a non-apoptotic regulated cell death program, has gained recent interest for its potential to effectively eliminate therapy-resistant cells. Leveraging ferroptosis, we report the development of an intrinsically therapeutic lipid-based nanoparticle platform through the incorporation of bioactive polyunsaturated fatty acid (PUFA)-containing vinyl ether-linked phospholipids, known as plasmalogens, into liposomes that encapsulate ferroptosis inducer RSL3 to effectively eliminate human OVCAR8 ovarian cancer cells. These bioactive lipids were chosen due to their ability to sensitize the cells toward ferroptosis, thus imparting on the nanocarriers a therapeutic role beyond their function as a delivery vehicle. The developed nanoparticle platform showed enhanced therapeutic efficacy compared to free RSL3 in OVCAR8 cells. In addition, by surface modification with hyaluronic acid (HA) through electrostatic layer-by-layer deposition, we further improved the therapeutic efficacy of the platform by increasing nanocarrier uptake in OVCAR8 cells. Further, we showed that the use of plasmalogen-containing nanocarriers for synergistic ferroptosis induction could be extended to nucleic acid cargo delivery via lipid nanoparticles (LNPs). Plasmalogen-containing LNPs that encapsulated small interfering RNA (siRNA) designed to downregulate expression of the gene responsible for ferroptotic evasion showed improved cancer cell cytotoxicity compared to the control LNPs without any plasmalogens. Overall, this integrated approach presents a novel strategy to tackle ovarian cancer, with the possibility of translation into an effective treatment approach for ovarian cancer patients who are not responsive to standard treatment modalities.
Recombinant measles virus (rMeV) vectors are promising platforms for vaccine development against emerging infectious diseases due to their safety, stability, and potent immunogenicity. However, conventional rMeV rescue systems frequently exhibit low efficiency, thereby constraining their scalability and throughput. In this study, we developed a modular, helper-virus-free and high-efficiency rescue platform based on an orthogonal transcription system utilizing orthogonal promoters and engineered RNA polymerases fused to an mRNA capping enzyme. This innovative system facilitated robust cytoplasmic manufacture of both genomic and auxiliary components, eliminating the need for helper virus co-infection (such as modified vaccinia virus) and enhancing rescue efficiency by more than 50-fold relative to traditional rescue approaches. Utilizing this technology, we demonstrated the versatility of the platform by successfully generating six rMeV-based vaccine antigen candidates from influenza virus, Pseudomonas aeruginosa, and Brucella spp. All rescued vaccine candidates exhibited stable transgene expression, sustained replication, and strong antigen production. Immunization studies in golden Syrian hamsters verified that the vaccine candidates elicited high titers of neutralizing and antigen-specific antibodies without any observable adverse effects. These results demonstrate that our orthogonal transcription-based platform facilitates the efficient and safe production of rMeV vectors and provides a proof-of-concept methodological framework for the rapid development of vaccine candidates.
Disease relapse remains the leading cause of failure following allogeneic hematopoietic cell transplantation (HCT). As novel prophylactic strategies increasingly aim to universally eliminate all forms of graft‑versus‑host disease (GVHD), how these approaches may inadvertently sacrifice graft‑versus‑leukemia (GVL) activity in the post‑transplant cyclophosphamide (PTCy) era is unclear. To evaluate the associations between time‑updated GVHD phenotypes and clinical outcomes, including relapse, non‑relapse mortality (NRM), and overall survival (OS), in patients undergoing PTCy‑based haploidentical or mismatched unrelated donor (MMUD) HCT. This was a retrospective cohort study using the Center for International Blood and Marrow Transplant Research registry. Participants included 7,055 patients with hematologic malignancies who received a first haploidentical or MMUD HCT with PTCy from 2013-2021. Associations with relapse, NRM and OS were evaluated using multi‑state time‑dependent Cox proportional hazards models and a multi‑state random survival forest (MS‑RSF). Time‑updated acute and chronic GVHD phenotypes included isolated grade II acute GVHD (aGVHD), grade III-IV aGVHD, mild chronic GVHD (cGVHD), and immunosuppressive therapy-requiring (IST‑requiring) cGVHD. IST‑requiring cGVHD without antecedent aGVHD was associated with a lower modeled relapse hazard compared with remaining GVHD‑free (Hazard Ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.89; False Discovery Rate (FDR)-adjusted p (q)=0.006) and lower overall mortality (HR 0.62; 95% CI, 0.53-0.73; q < 0.001). In contrast, grade III-IV aGVHD was associated with significantly higher modeled NRM (HR, 3.15; 95% CI, 2.57-3.84; q < 0.001). Mild cGVHD and isolated grade II aGVHD showed intermediate patterns without consistent associations. These associations were directionally consistent across multiple analytic approaches, including standard time‑dependent Cox regression, dynamic and fixed landmark analyses, and MS‑RSF. In this large PTCy‑treated mismatched donor cohort, IST‑requiring cGVHD was the GVHD phenotype most consistently associated with lower relapse incidence, whereas severe aGVHD was associated with higher NRM. These findings highlight heterogeneity in GVHD phenotypes and suggest that strategies distinguishing toxic acute GVHD from chronic alloreactivity patterns may better balance morbidity and long‑term disease control. Given that relapse remains the predominant cause of post‑transplant mortality, approaches aiming to universally eliminate all GVHD warrant careful reconsideration.
The precise mechanistic role of Interleukin-13 receptor alpha-2 (IL-13Rα2) in colorectal cancer (CRC) remains elusive, specifically regarding whether it functions as an active signaling receptor or a passive decoy. Its unique role in metastatic phenotypic plasticity remains poorly understood. We identified IL-13Rα2 as a powerful oncogenic signaling hub that significantly increases CRC cell proliferation, migration, and colony formation using shRNA knockdown and CRISPR activation to modify IL-13Rα2 across a range of CRC cell lines with different baseline characteristics. Most importantly, we found that its regulation of the epithelial-mesenchymal transition (EMT) is highly context-dependent. IL-13Rα2 controls the mesenchymal phenotype in highly plastic cells in a partial-EMT (p-EMT) stage (such as SW-480 and SW-620). Its removal completely reverses EMT and collapses core plasticity-driving nodes, such as AGR2 and p63. On the other hand, IL-13Rα2 precisely functions as a phenotypic amplifier limited by the cellular epigenetic landscape in strictly epithelial cells (such as HT-29), where it controls cellular survival but does not initiate EMT. The STAT6 signaling cascade is monopolized by IL-13Rα2. Targeted downregulation eliminates IL-13-induced STAT6 phosphorylation, which in turn causes severe cell cycle dysregulation marked by a delayed G1/S transition and intra-S phase arrest. In conclusion, our research demonstrates that IL-13Rα2 is a crucial, context-dependent signaling receptor that maintains the p-EMT state and malignant progression via the STAT6 axis, making it a precise therapeutic target for advanced, phenotypically plastic colorectal cancer.
Aryl hydrocarbon receptor (AhR) agonist facilitates the repair of damaged intestinal barriers in experimental colitis. Nobiletin, a distinct polymethoxyflavone present in citrus peel, has been reported to mitigate Dextran sulfate sodium (DSS) induced colitis in mice. Nevertheless, its specific roles in improving the colonic barrier homeostasis through AhR remain to be fully defined. This study was designed to determine the effects of nobiletin on AhR and intestinal barrier integrity during colitis and to uncover the involved mechanism. Models of intestinal injury were established using DSS-treated mice and TNF-α-stimulated HT-29 cells, followed by intervention with nobiletin. A series of techniques, including immunofluorescence, immunohistochemistry, hematoxylin and eosin (H&E)/alcian blue-periodic acid-Schiff (AB-PAS) staining, fluorescein isothiocyanate-dextran (FITC-dextran) flux assay, quantitative real-time polymerase chain reaction (qPCR), and Western blotting, were employed to assess its effects on colitis progression and barrier function. Mechanistic insights were gained using the AhR antagonist CH223191, AhR-knockout mice, and AhR-specific siRNA. The findings indicated that nobiletin markedly alleviated DSS-induced colitis, enhanced the expression of tight junction proteins, and improved barrier function. Concurrently, it acts as an AhR agonist and increases its downstream gene, CYP1A1. Crucially, these beneficial effects were eliminated upon pharmacological inhibition or genetic ablation of AhR. In summary, nobiletin attenuates intestinal epithelial barrier impairment in colitis involving activation of the AhR pathway, highlighting its therapeutic potential for conditions characterized by barrier dysfunction.
To solve the problem of rigid motion artifacts caused by patient movement and gantry vibration during long-duration cone-beam computed tomography (CBCT) using geometric parameter decoupling and motion-constrained optimization. Using a motion estimation framework based on 3D-2D rigid registration, the rigid motion parameters were categorized into out-of-plane and in-plane motions, and a stepwise optimization sequence was designed to decouple the mutual interference among the parameters. In response to dynamic evolution of artifact characteristics from multi-contour overlap to edge blurring during the iterative process, a progressive cost function was formulated to facilitate an adaptive transition of the optimization objective from projection data consistency constraints to structural detail recovery. To address the issue of multi-solution in 3D-2D registration and the potential spatial misalignment introduced during iteration, a motion estimation constraint mechanism was incorporated to eliminate global bias, thereby enhancing the algorithm's convergence. The proposed algorithm accurately estimated rigid motion trajectories and restored the images via motion compensation. On head simulation data, this model achieved optimal quantitative metrics across 3 motion levels, improved PSNR by 2.1% and SSIM by 2.9%, and reduced RMSE by 6.5% compared to the suboptimal methods. Additional validation on knee simulation and real porcine data further demonstrated its efficacy and generalization capability. The proposed rigid motion artifact correction algorithm demonstrates good performance in estimating motion trajectories and compensating for image artifacts, thus providing a viable and robust solution for suppressing rigid motion artifacts in clinical CBCT imaging. 目的: 为了解决锥形束计算机断层扫描（CBCT）长时间扫描过程中因患者运动和机架抖动导致的刚性运动伪影问题，我们提出一种基于运动参数解耦与运动约束驱动的CBCT刚性运动校正方法。方法: 采用基于3D-2D刚性配准的运动估计框架，将刚性运动参数划分为层间运动和层内运动，并设计分步优化顺序解耦参数间的相互干扰。针对迭代过程中伪影表征由多轮廓重叠向边缘模糊的动态演变，构建渐进式代价函数，实现优化目标从投影数据一致性约束向结构细节恢复的适应性过渡。为解决3D-2D配准的多解性问题及迭代过程中可能引入的图像空间位置偏移，引入运动估计约束机制消除全局偏差，从而增强算法收敛性。结果: 所提算法能够准确估计刚性运动轨迹并运动补偿修复CBCT图像。在头部仿真数据中，本文方法在3种运动程度下均取得最优量化指标。相较于次优方法，峰值信噪比（PSNR）平均提升约2.1%，结构相似性（SSIM）平均提升约2.9%，均方根误差（RMSE）平均降低约6.5%。在膝关节仿真与真实猪肢干数据上的实验结果进一步验证了算法的有效性与泛化能力。结论: 本文提出的刚性运动伪影校正算法在估计运动轨迹与抑制图像伪影方面具有良好性能，为临床CBCT成像中刚性运动伪影的抑制提供了一种可行且稳定的解决方案。.
Standard endoscopic gynecomastia surgery, while offering better cosmetic outcomes than open procedures, is often hindered by suboptimal visualization of the glandular-adipose interface, instrument clashing due to multiple concealed ports, and the risk of nipple-areolar complex (NAC) ischemia. This paper describes a technical modification using a single-incision platform and advanced imaging to overcome these limitations. The authors utilize the GelPOINT Mini platform for single-site access through a concealed 3-cm incision behind the anterior axillary fold. To enhance visualization, the VISERA ELITE III Yellow Enhancement (YE) imaging system is employed. This technology brightens fat-rich yellow tissues, allowing for a clearer distinction between the glandular tissue and overlying fat. This technique is specifically indicated for Simon Grade IIa-IIb patients with firm glandular tissue and minimal skin excess. The single-incision approach eliminates instrument clashing and poor triangulation associated with multi-port techniques. The use of YE imaging facilitates a more precise dissection in the plane beneath the NAC, reducing the risk of vascular compromise, residual pathology, and contour irregularities. The integration of a single-port platform with Yellow Enhancement imaging offers a refined approach to endoscopic gynecomastia surgery. By improving visualization and ergonomics, this modification enhances surgical precision and aesthetic outcomes while minimizing visible scarring.
Targeted protein degradation is an emerging concept of drug discovery to selectively eliminate the pathogenic proteins by activating their degradation in cells. The proteolysis-targeting chimeras (PROTACs) are bifunctional small molecules that induce the degradation of a protein of interest (POI) by proteasome. Here we describe a method that utilizes an ssrA-based BacPROTAC (bacterial PROTACs) to target the drug-resistant proteins CTX-M-14, a class A β-lactamase commonly found in extended-spectrum beta-lactamase (ESBL) plasmids of antimicrobial resistance (AMR) bacteria. This strategy could resensitize the drug-resistant bacteria and revive previously disregarded antibiotics, opens up a new avenue for therapeutic development of AMR bacteria.
All-solid-state Marx generators have shown broad application prospects in fields such as dielectric barrier discharge, biomedical engineering, and environmental treatment. When pursuing nanosecond-scale fast-front pulses, the extremely high voltage change rate (dv/dt) can readily induce Miller false turn-on in switching devices. Meanwhile, conventional isolated driving schemes with robust noise immunity typically rely on bulky independent power supplies, which severely limit the development of highly compact pulsed power systems. To address these challenges, this paper proposes a compact composite magnetic isolation drive circuit that eliminates the need for an independent high-voltage isolated power supply. The proposed topology integrates a passive negative-voltage bootstrap network with an active Miller clamp (AMC) branch. Through the establishment of a transient mathematical model and ablation experiments, the synergistic immunity mechanism of the composite drive is revealed: the steady-state negative bias generated by bootstrapping, together with the low-impedance discharge path provided by the AMC, physically blocks the path through which high-frequency displacement currents could otherwise elevate the gate potential. Quantitative parasitic parameter scanning shows that even with a severe gate stray inductance of 50 nH, the proposed scheme maintains the transient gate voltage within the safe operating area of the device. Based on the above investigation, a 20-stage SSMG experimental prototype was developed. Experimental results demonstrate that the system operates stably under a wide load range (2-20 kΩ) at a repetition frequency of 1 kHz, successfully outputting fast-front high-voltage pulse sequences with an amplitude of 20 kV and a rise time of 22.9 ns.
A residual false lumen after type A aortic dissection repair may rarely serve as an embolic route to the cerebral circulation. A woman in her 60s underwent ascending aortic replacement for Stanford type A aortic dissection, leaving a residual patent dissection involving the supra-aortic branches and the descending aorta. Despite receiving anticoagulant and antiplatelet therapies, the patient developed recurrent multifocal cerebral infarctions. Transesophageal echocardiography (TEE) demonstrated an entry tear in the descending aorta communicating from the true lumen to the false lumen. Flow became markedly stagnant toward the proximal false lumen, with thrombus-like echogenic material. Four-dimensional computed tomography (4DCT) confirmed delayed retrograde flow ascending within the false lumen toward the arch. Total arch replacement was performed to eliminate the suspected embolic route. Intraoperative findings confirmed thrombotic material within the false lumen. No recurrent cerebral infarctions were observed postoperatively.
Perfluorooctane sulfonic acid (PFOS) is a persistent perfluoroalkyl substance known to exert adverse effects on soil and terrestrial ecosystems. However, the toxicological risks of its substitutes, particularly sodium p-perfluorinated nonenoxybenzene sulfonate (OBS), and their impacts on perennial plants and food-chain transfer remain insufficiently understood. Here, mulberry (Morus alba) seedlings were used as a model perennial species to compare the phytotoxic effects of PFOS and OBS. PFOS exerted markedly stronger inhibitory effects than OBS, as evidenced by significant reductions in plant height, biomass, and photosynthetic performance. Transcriptomic analyses revealed that both compounds primarily modulated general stress-responsive pathways, whereas OBS induced substantially fewer differentially expressed genes than PFOS, indicating a lower level of molecular disturbance. PFOS accumulation in mulberry was dominated by root retention, with approximately 85.2% retained in roots, followed by leaves (around 14.3%) and stems (around 0.5%). To assess PFOS toxicity along the mulberry-silkworm PFOS exposure, silkworms (Bombyx mori) were fed PFOS-contaminated mulberry leaves. Low PFOS exposure did not affect silkworm growth or silk production, whereas high exposure levels caused growth retardation and impaired cocoon formation. Approximately 58.6% of ingested PFOS was eliminated via excretion. Transcriptomic analysis further revealed that reduced silk production under high PFOS exposure was associated with the downregulation of genes involved in silk protein biosynthesis and processing, including polypeptide N-acetylgalactosaminyltransferase (GALNT). Collectively, these findings improve our understanding of PFOS- and OBS-induced stress responses in mulberry and highlight the potential of mulberry as a candidate species for PFOS uptake and provide preliminary information relevant to future phytoremediation research.
Nipah virus (NiV) poses a major risk to global public health due to its high infectivity and associated mortality rates. Currently, no licensed vaccines or antiviral medications are available for NiV infection, leaving clinical management limited to supportive care. The viral receptor glycoprotein responsible for binding NiV to host cell receptors (ephrin-B2/B3) represents an ideal therapeutic target. This study proposes a novel peptide-ligand conjugate (PLC) immunotherapeutic approach that exploits pre-existing immune responses in NiV-endemic populations to selectively target and eliminate infected cells. We employed biomolecular modeling (in silico) to establish binding affinities and perform docking studies using a compound library obtained from the MolProphet database. A non-cleavable oxime linker was selected to enhance physical stability and ensure robust conjugation between ligand and peptide components. The peptide was engineered to contain immunogenic minimal epitope regions derived from measles, mumps, and rubella vaccines, selected based on their high immunization rates and long-lived memory responses in individuals residing in NiV-endemic areas. The PLC design demonstrated selective binding capacity to a transmembrane protein present on NiV-infected cells. The oxime linker provided enhanced stability, and the peptide epitope design successfully incorporated regions associated with established long-term immunity. This PLC system represents a promising framework for antiviral therapeutic development by harnessing pre-existing immune recognition to promote selective clearance of NiV-infected cells. The findings highlight critical structural components and functional roles of PLCs in therapeutic development, including drug target screening and rational design strategies for enhancing targeting specificity and molecular stability. Future work should focus on experimental validation of the computational predictions and in vitro/in vivo efficacy studies.
Agricultural systems are major sources of methane emissions, contributing to climate change with potential downstream effects on population health. West Africa faces a growing burden of non-communicable diseases (NCDs) alongside agricultural intensification, yet the relationship between agricultural emissions and NCD mortality remains unexplored. We examined whether changes in agricultural methane emissions were associated with NCD mortality trends across West African countries. We conducted an ecological panel study of 11 West African countries from 2015 to 2020 using World Bank World Development Indicators data. The exposure was agricultural methane emissions, measured in carbon dioxide equivalents (Mt CO₂e). The primary outcome was the probability (%) of dying from NCDs between exact ages 30 and 70 for both sexes combined; sex-stratified outcomes for women and men were examined as secondary analyses. We classified countries by emission trajectory: decreasing (> 5% reduction), stable, or increasing (> 10% increase). For each outcome we estimated associations using pooled ordinary least squares, within-country fixed effects, mixed effects models with random intercepts, and a descriptive group-by-period comparison of NCD mortality trajectories between The Gambia (largest emission reduction: -28.3%) and other countries. Sensitivity analyses assessed robustness to influential observations, functional form, and temporal specification. For both sexes combined, pooled analysis suggested an inverse cross-sectional association between agricultural methane and NCD mortality (β = -0.085; 95% CI: -0.126 to -0.043; p < 0.001). However, within-country fixed effects models showed no association (β = 0.027; 95% CI: -0.081 to 0.134; p = 0.62), indicating confounding by time-invariant country characteristics. The intraclass correlation coefficient was 0.984, indicating 98.4% of variance occurred between countries. A descriptive group-by-period comparison found no differential change for The Gambia versus other countries (0.62 percentage points; 95% CI: -0.78 to 2.03; p = 0.39). Sex-stratified analyses were consistent: the pooled inverse association was present for both women (β = -0.077; p = 0.001) and men (β = -0.096; p = 0.004) but was eliminated under fixed effects (women p = 0.27; men p = 0.88), and excluding Nigeria reversed the pooled association (both sexes β =  + 0.091, p = 0.014), confirming it was driven by a single influential country. Agricultural methane emission reductions were not associated with short-term changes in NCD mortality in West Africa. The high between-country clustering suggests that stable country-level factors including health system capacity, socioeconomic development, and baseline disease burden are more strongly associated with NCD mortality patterns. Longer follow-up periods and individual-level studies are needed to evaluate potential health co-benefits of agricultural emission reductions.
Today we are accustomed to the idea that eating certain foods can help to support the immune system. Over the last two decades, this familiar narrative has been bolstered by the rise of microbial science and the growing popularity of biome-led nutrition, which encourages eaters to nourish the flora and fauna of their guts for the sake of better overall health. While our current preoccupation with the microbiome can be dated to the launch of the Human Microbiome Project in 2007, its origin story can be traced much further back. It begins with work undertaken by scientists and physicians around the turn of the 20th century aimed at understanding the significance of microbes in the digestive system. One of those, the Russian zoologist Élie Metchnikoff (1845-1916), is perhaps best remembered as the founder of modern immunology, and his work on phagocytosis-the capacity of certain specialized cells to engulf and eliminate intruders-earned him the Nobel Prize in 1908. According to Metchnikoff, the gut was the "engine of senility," where pathogenic bacteria multiplied and threatened to overwhelm the body's defenses. Transforming the belly into a battleground where good bacteria went to war with bad, Metchnikoff's influential work extended his theorization of organic immunity as a form of intercellular defense to the vexed question of what to eat and created the foundation for Emily Martin's "immunological body," an understanding of the body that likens it to a nation state, defined through the careful maintenance of the boundary between self and non-self, at this intersection of dietetics and immunology.
Compressed sensing formulations that target an $\ell _{0}$ -norm objective are inherently nonconvex and discontinuous. In this article, a global optimization problem with a power-mean function is first formulated for compressed sensing. To mitigate the numerical instability of minimizing the power-mean function with a large negative exponent, the problem is reformulated as a sequential majorization-minimization (MM) problem with iteratively reweighted convex surrogate functions at different anchor points. To eliminate the dependency of the solution quality on anchor points, multiple neurodynamic optimization models are employed to seek global optimal solutions collaboratively through repeated reinitialization using a particle swarm optimization rule. Extensive experiments demonstrate that the proposed method achieves superior performance compared to 14 state-of-the-art algorithms in terms of signal sparsity and reconstruction accuracy.
Compared with heterosexual persons, non-heterosexual persons have worse mental health. Sexual Minority Stress Theory (SMST) explains the disparity as resulting from stigma and discrimination. To the extent that heterosexual genetic relatives reared with non-heterosexual persons also have worse mental health, SMST is falsified. We conducted a systematic meta-analysis of studies containing family-genetic comparison data to interrogate the empirical support for SMST. We systematically identified 17 empirical studies in which twins or non-twin siblings reported on both their sexual orientation and their mental health. Subsequently, we conducted a multilevel meta-analysis, focusing on the degree to which any sexual orientation disparity in mental health diminished with genetic relatedness. Most of the mental health disparities between non-heterosexual and heterosexual persons were eliminated after controlling for family-genetic factors. The mental health disparity between non-heterosexual and heterosexual persons is reduced by up to two-thirds once familial background factors are accounted for by comparing monozygotic twins discordant for sexual orientation. This suggests that shared familial causes, and not minority stress, are the most important causes of mental health disparities in non-heterosexual persons.
: D-malic acid is one of the two stereoisomers that make up racemic (DL-) malic acid, which is commonly produced through chemical synthesis. In contrast, naturally occurring malic acid found in fruits, fruit juices, and wines consists almost exclusively of the L-isomer, with little or no D-malic acid being present. Therefore, the presence of D-malic acid in a natural product such as wine or fruit juice serves as an indicator that racemic DL-malic acid has been artificially added. To validate the performance of the D-Malic acid test kit (Enzytec™ Liquid D-Malic acid) for the determination of D-malic acid in food such as soft drinks, fruit juices, tomato juice, and wine. D-malic acid is oxidized by NAD+ in the presence of D-malate dehydrogenase to pyruvate and carbon dioxide. The NADH produced is equivalent to D-malic acid converted and is measured at 340 nm. α-Ketoglutaric acid, sulfite, and meso-tartaric acid do not interfere at or below 0.5 g/L, 0.5 g/L and 0.2 g/L, respectively. L-tartaric acid reacts and leads to a creep reaction which can be eliminated by precipitation or extrapolation. LOD is at 4 mg/L for 100 µL. The linear measurement range is 14 mg/L to 500 mg/L for a test volume of 100 µL. Recovery was checked in grape juice, tomato juice, lemonade, pineapple juice, currant juice, bitter lemon and apple juice and resulted in mean recoveries between 90 and 103%. Trueness was also evaluated using reference wines and a fruit juice CRM. For automation, two applications with different test volumes were validated. Linearity is given from 5 up to 2500 mg/L. The method is robust and accurate for manual and automated applications. The method was approved as AOAC Official Method of Analysis℠. The kit contains two ready-to-use components which make handling easy and suitable for automation.
Periodontitis, characterized by progressive alveolar bone resorption and periodontal defect formation, remains a major clinical challenge driven by bacterial infection and a dysregulated inflammatory immune microenvironment. Neutrophils, as the predominant innate immune cells, accumulate at infected sites to eliminate microbes but concurrently suppress osteoblast function, thereby impairing bone formation and accelerating alveolar bone loss. Lipopolysaccharide-preconditioned dental follicle stem cell-derived small extracellular vesicles (L-DFSC-sEV) exhibit potent immunomodulatory activity, facilitating the clearance of proinflammatory neutrophils and attenuating neutrophil hyperactivation, and reshaping the periodontal immunoregulatory microenvironment. However, the therapeutic efficacy of sEV is often hindered by the hostile infectious and inflammatory environment, as well as the lack of an appropriate delivery system tailored to periodontal conditions. To overcome these limitations, we developed a multifunctional, dynamically cross-linked hydrogel comprising gelatin, oxidized chondroitin sulfate, and epigallocatechin gallate at physiological pH, which encapsulates L-DFSC-sEV (L-DFSC-sEV@GCSE). This hydrogel exhibits excellent tissue adhesion, self-healing capability, antibacterial activity, and immunoregulatory properties, thereby creating a favorable microenvironment for sustained sEV release. In a rat periodontal defect model, L-DFSC-sEV@GCSE markedly enhanced sEV retention and delivery, effectively controlled infection and inflammation, modulated the osteoimmune microenvironment, and significantly promoted periodontal tissue regeneration.
To assess the safety of aortic intravascular ultrasound (IVUS) immediately after proximal repair in acute type A aortic dissections (ATAADs) and to identify malperfusion early, guiding interventions to restore arterial flow, limit end-organ damage, and improve outcomes. In this prospective cohort study, 50 consecutive patients with ATAAD were stratified according to clinical presentation into 2 groups; group 1, no malperfusion at presentation, and group 2, malperfusion at presentation. All patients underwent standard emergent operative repair and then were assessed with IVUS intraoperatively for evidence of distal malperfusion. Primary outcome included a composite of death, mesenteric, renal and limb ischemia, and vascular complications. Secondary outcomes included length of intensive care unit and hospital stay. Follow-up was completed at 30 days post-op or the date of discharge. Primary outcome was observed in 10 patients (20.0%), with 7 deaths, 2 vascular complications, and 1 case of new permanent dialysis. IVUS identified distal arterial malperfusion in 5 patients after proximal aortic repair, who underwent emergent additional vascular interventions to correct the residual malperfusion. These interventions resulted in no cases of death, paralysis, renal, bowel, or limb ischemia. Individuals requiring additional vascular procedures had a similar length of intensive care unit and total stay compared with group 1. IVUS is safe in ATAAD and provides immediate guidance in the treatment of residual malperfusion after proximal repair. This technique eliminates any delays, provides immediate distal perfusion assessment, limits end-organ damage, and is associated with excellent clinical outcomes. The results of this study warrant further investigation.
Triphenyl phosphate (TPHP), an emerging pollutant with neurotoxic and reproductive toxicity, severely threatens global food safety and human health through environmental exposure risks and bioaccumulation. A rapid and non-destructive detection method for TPHP was established using terahertz time-domain spectroscopy (THz-TDS). This study systematically analyzed the impact of window functions on TPHP fingerprint spectra and integrated DFT calculations, chemometric analysis, and baseline correction algorithms for TPHP quantitation and qualitation in real samples. Boxcar window optimally retained absorption peaks of TPHP at 0.94, 1.21, 1.45, and 1.70 THz. B3LYP-D3/6-31G(d,2p) basis set effectively corrected the frequency shift caused by weak intermolecular interactions, resulting in a high degree of agreement between the theoretical and experimental spectra in 0.1-2.0 THz range. AirPLS algorithm effectively eliminated matrix interference in real samples, enabling accurate analysis of TPHP with a LOD of 0.09%, which advanced the practical application of THz-TDS in food safety and environmental monitoring.