This study aimed to identify heterogeneous subtypes of mouth opening function in patients after oral cancer surgery and explore factors associated with mouth opening function profiles. We recruited 305 patients who underwent oral cancer surgery at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, between April and September 2025. Data were collected using a general information questionnaire, measurements of maximum interincisal opening, the Gothenburg Trismus Questionnaire, and the Tampa Scale of Kinesiophobia for Temporomandibular Disorders. Latent profile analysis (LPA) was used to identify subtypes of mouth opening function, followed by multinomial logistic regression to determine the associated factors. Three subtypes were identified through LPA among included postoperative patients with oral cancer: well-functioning with mild symptoms (28.2%, n = 86), moderate dysfunction with pain (50.2%, n = 153), and severe dysfunction with severe symptoms (21.6%, n = 66). Compared with the first subtype, preoperative mouth opening restriction (odds ratio [OR] = 2.830, P = 0.018) and a higher level of mandibular movement avoidance behavior (OR = 1.394, P = 0.001) were associated with the second subtype. Preoperative mouth opening restriction (OR = 5.624, P = 0.001), a higher level of mandibular movement avoidance behavior (OR = 1.304, P = 0.020), and receipt of flap reconstruction (OR = 13.144, P = 0.002) were associated with the third subtype. Of note, only a small number of patients in Class 3 did not receive flap reconstruction, which resulted in a wide confidence interval. This association should therefore be interpreted cautiously. Using a subjective-objective combined assessment method, this study identified three distinct mouth opening function subgroups in postoperative oral cancer patients. Each subgroup exhibited distinct characteristics and was associated with a combination of factors. These findings may provide a useful basis for early identification and for developing future targeted intervention strategies according to the characteristics of each subtype.
Medial opening wedge high tibial osteotomy is a successful procedure for correction of varus malalignment in isolation or in combination with other knee ligamentous and cartilage procedures. This article describes a technique for medial opening wedge high tibial osteotomy using a Hintermann distractor, which allows better control of the osteotomy gap opening and the posterior tibial slope. Preoperative digital planning is undertaken. A small longitudinal incision and a minimally invasive approach are performed to expose the proximal tibia. The Hintermann distractor is applied over 2 guide wires inserted divergently proximal and distal to the transverse osteotomy. The Hintermann distractor is used to open the osteotomy gap and maintain or change the posterior tibial slope according to the preoperative plan. Unimpeded access is provided, with no instrumentation in the gap, and this allows precise positioning of an allograft bone wedge, which is followed by fixation with an angular stable locking plate. In this technique, the Hintermann distractor serves as an outrigger that provides support to the osteotomy and offers rotational control to change the posterior tibial slope if desired.
The public health service (ÖGD) has had little presence in human medicine studies in Germany to date. As a result, students lack knowledge about its practical tasks, meaning that the ÖGD is rarely considered when choosing a career. This situation contributes significantly to the shortage of young doctors in public health departments. Elective placements during the practical year are intended to attract students to the ÖGD; however, evaluations indicate that the offered places are not being filled, despite the positive assessment. Project description To promote interest in the ÖGD at an early stage and in a low-threshold manner, an extracurricular course was developed at Justus-Liebig-Universität Gießen as a supplementary elective in the interdisciplinary area of Health Economics, Health System, and Public Health. In the summer semester of 2025, a 90-minute bathing water inspection was held for the first time in cooperation with the Giessen Health Authority. The aim was to provide students with practical insights into the work of the ÖGD in the fields of water and environmental hygiene, while also establishing personal contact with the authorities' employees. Feedback from participants showed that the event was found to be enriching both professionally and in terms of career orientation. In contrast to clinical placements or PJ elective terms, the format allowed for very low-threshold access without requiring students to choose between other subject areas. Extracurricular elective courses such as bathing water inspections can serve as a complementary strategy to raise students' awareness of the ÖGD at an early stage and thus contribute to the long-term recruitment of young talent to public health service. Der Öffentliche Gesundheitsdienst (ÖGD) hat im Humanmedizinstudium bislang eine geringe Präsenz. Dadurch fehlt es Studierenden an Kenntnissen über seine praktischen Aufgaben, sodass der ÖGD bei der Berufswahl kaum berücksichtigt wird. Diese Situation trägt wesentlich zur ärztlichen Nachwuchslücke in den Gesundheitsämtern bei. Wahltertiale im Praktischen Jahr sollen Studierende für den ÖGD gewinnen, doch Auswertungen zeigen, dass die angebotenen Plätze nicht ausgeschöpft werden, obwohl die Evaluationen positiv ausfallen. Projektbeschreibung Um das Interesse am ÖGD frühzeitig und niederschwellig zu fördern, wurde an der Justus-Liebig-Universität Gießen ein extracurriculares Lehrangebot als ergänzendes Wahlangebot zum Querschnittsbereich 3 Gesundheitsökonomie, Gesundheitssystem und Öffentliches Gesundheitswesen entwickelt. Im Sommersemester 2025 fand erstmals eine 90-minütige Badegewässerbegehung in Kooperation mit dem Gesundheitsamt Gießen statt. Ziel war es, Studierenden praxisnah Einblicke in die Arbeit des ÖGD im Bereich Wasser- und Umwelthygiene zu ermöglichen und gleichzeitig den persönlichen Kontakt zu Mitarbeitenden der Ämter herzustellen.Die Rückmeldungen der Teilnehmenden zeigen, dass die Veranstaltung sowohl fachlich als auch in Hinblick auf die Berufsorientierung als bereichernd empfunden wurde. Im Unterschied zu Famulaturen oder PJ-Wahltertialen ermöglicht das Format einen sehr niederschwelligen Zugang, ohne dass Studierende sich gegen andere Fachgebiete entscheiden müssen.Extracurriculare Wahlangebote wie die Badegewässerbegehung können als ergänzende Strategie dienen, Studierende frühzeitig für den ÖGD zu sensibilisieren und damit langfristig zur Nachwuchsgewinnung beizutragen.
This study proposes an integrated framework for fatigue crack monitoring, propagation prognostics, and condition-based maintenance of aircraft aluminum alloy structures with large cutouts. A flexible planar eddy current sensor array is developed to achieve real-time, multi-channel monitoring of crack initiation and growth under laboratory fatigue testing conditions, with a minimum detectable crack length of 0.3 mm and a spatial resolution of 2 mm. A dynamic Bayesian network combined with a particle filter and the Walker crack growth model is employed to probabilistically forecast crack propagation by continuously updating model parameters using sensor data. Experimental results demonstrate that the proposed method significantly reduces prognostic uncertainty and improves accuracy compared with deterministic models. Based on the estimated crack evolution, a health index-driven condition-based maintenance strategy is established, enabling rational selection of repair methods and maintenance timing. The results show that the proposed approach effectively supports safe and economical maintenance decision-making for aircraft structures.
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As device miniaturization approaches its physical limits, the performance enhancement of silicon electronics has become increasingly difficult, shifting attention toward 2D semiconductors as potential alternatives. Among these, monolayer platinum diselenide (PtSe2) has garnered significant interest as a next-generation channel material for nanoelectronics. Distinguished by its exceptional theoretical carrier mobility-six times higher than that of MoS2-and remarkable air stability, monolayer PtSe2 emerges as a promising candidate for advanced semiconductor applications. However, achieving uniform growth of high-quality monolayer PtSe2 presents challenges. In this study, we report the first successful growth of high-quality monolayer PtSe2 films using an optimized metal-organic chemical vapor deposition (MOCVD) process. We confirmed the uniform growth of the monolayer films over an area of 1.5 cm × 1.5 cm through various optical analyses, proving superior controllability of precursor flow and growth rate. Oxygen was introduced during the growth process to effectively eliminate carbon impurities, resulting in a high-quality film. Finally, we demonstrated an array-level transistor employing the monolayer PtSe2 as the channel, achieving low off-current and a maximum ION/IOFF ratio of 8.31 × 104. We succeeded in growing an industrially applicable level of semiconducting PtSe2 film, thereby highlighting the advantages of our growth method for future electronic applications.
Temporomandibular joint (TMJ) disc displacements (DD) and osteoarthritis (OA) are types of intra-articular temporomandibular disorders (iTMDs) commonly accompanied by pain and dysfunction. We systematically evaluated the literature to determine the comparative effectiveness of treatments for painful iTMDs. We searched seven databases for randomized clinical trials (RCTs) evaluating the effect of medications, used alone or adjunctively, on pain intensity and mouth opening. Risk of bias and certainty of evidence were assessed using Cochrane's RoB 2.0 tool and the CINeMA approach. Data were synthesized using frequentist network meta-analyses. We included twenty-three RCTs involving 1264 patients. In TMJ-DDs, multiple interventions demonstrated statistically significant short-term (≤ 3 months) pain reductions, with only MESNA (sodium 2-mercaptoethanesulfonate) and arthrocentesis with hyaluronic acid (HA) also showing statistically significant effects in the long-term (> 3 months). Several interventions were also associated with statistically significant improvements in mouth opening. In TMJ-OA, palmitoylethanolamide and avocado-soybean extract showed statistically significant short-term pain reductions, while glucosamine hydrochloride or glucosamine sulfate combined with HA were associated with statistically significant long-term improvements in pain and mouth opening. No intervention showed significant short-term effects on mouth opening in TMJ-OA. For both TMJ-DD and OA, estimates were generally supported by low or very low certainty of evidence and were below the minimal clinically important difference. Overall, the evidence indicates limited and inconsistent clinical benefits, and no available treatment can be recommended with confidence. This study highlights the urgent need for additional high-quality RCTs to generate robust and clinically meaningful evidence to guide practice in painful iTMDs.
Odontogenic space infections can rapidly progress to severe complications, necessitating reliable biomarkers for early assessment and monitoring of treatment response. C-reactive protein (CRP) has been shown to be a sensitive indicator of systemic inflammation. To evaluate the use of serum CRP levels as a monitoring tool in patients with odontogenic space infections and correlate serial CRP changes with clinical recovery. Thirty-six patients with odontogenic space infections requiring surgical intervention were considered for this research. Serial serum CRP measurements were performed at baseline (Day 0, Day 3, Day 5, and Day 7) using an immunoturbidimetric assay. Clinical parameters, including pain (visual analog scale), swelling, and mouth opening, were recorded at the same intervals. Data were statistically analyzed. Mean CRP levels significantly decreased from 84.2 ± 20.6 mg/L on Day 0-9.6 ± 4.3 mg/L on Day 7 (P < 0.001). Pain, swelling, and mouth opening improved in parallel with CRP decline. CRP and pain were found to have strong positive relationships (r = 0.71) along with swelling (r = 0.74), and also for hospital stay (r = 0.69). There was a negative correlation noted with mouth opening (r = -0.65). Higher baseline CRP (>100 mg/L) and it was associated with prolonged hospitalization. Serial serum CRP measurements reliably reflect clinical improvement in odontogenic space infections and can serve as a practical biomarker for monitoring disease progression and treatment response. Résumé Contexte:Les infections des espaces odontogènes peuvent rapidement évoluer vers des complications graves, nécessitant des biomarqueurs fiables pour une évaluation précoce et le suivi de la réponse au traitement. La protéine C-réactive (CRP) s’est révélée être un indicateur sensible de l’inflammation systémique.Objectif:Évaluer l’utilité du dosage de la CRP sérique comme outil de suivi chez les patients atteints d’infections des espaces odontogènes et corréler les variations de la CRP avec la guérison clinique.Matériel et méthodes:Trente-six patients atteints d’infections des espaces odontogènes nécessitant une intervention chirurgicale ont été inclus dans cette étude. Des dosages sériés de la CRP sérique ont été effectués à l’inclusion (jours 0, 3, 5 et 7) par une méthode immunoturbidimétrique. Les paramètres cliniques, notamment la douleur (échelle visuelle analogique), l’œdème et l’ouverture buccale, ont été enregistrés aux mêmes intervalles. Les données ont été analysées statistiquement.Résultats:Les taux moyens de CRP ont diminué significativement, passant de 84,2 ± 20,6 mg/L au jour 0 à 9,6 ± 4,3 mg/L au jour 7 (P < 0,001). La douleur, l’œdème et l’ouverture buccale se sont améliorés parallèlement à la diminution de la CRP. Une forte corrélation positive a été observée entre la CRP et la douleur (r= 0,71), ainsi qu’avec l’œdème (r = 0,74) et la durée d’hospitalisation (r = 0,69). Une corrélation négative a été notée avec l’ouverture buccale (r = −0,65). Un taux de CRP initial élevé (> 100 mg/L) était associé à une hospitalisation prolongée.Conclusion:Les mesures sérielles de la CRP sérique reflètent de manière fiable l’amélioration clinique des infections des espaces odontogènes et peuvent servir de biomarqueur pratique pour le suivi de la progression de la maladie et de la réponse au traitement.
Retromolar trigone carcinoma is a relatively rare malignancy; however, owing to its complex anatomy, it is often diagnosed at an advanced stage. Surgical resection frequently results in complex defects of the maxilla, mandible, and buccal mucosa. Although free-flap reconstruction is commonly used for such defects, reports focusing on defect-oriented flap configuration strategies are limited. In this study, the authors aimed to evaluate the usefulness and clinical significance of a pouch-type flap configuration for the 3-dimensional reconstruction of extensive retromolar defects. Consecutive patients who underwent retromolar defect reconstruction using a pouch-type flap configuration at our institution between January 2022 and January 2025 were retrospectively reviewed. Postoperative outcomes were assessed by measuring maximal mouth opening and objective radiologic evaluation of cheek depression using computed tomography. Eleven patients were included, and complete flap survival was achieved in all cases. Postoperative maximal mouth opening ranged from 18 to 45 mm. Cheek contour evaluation demonstrated excellent outcomes in 5 cases, good outcomes in 3 cases, and fair outcomes in 1 case. The remaining 2 cases could not be evaluated because early tumor recurrence precluded postoperative follow-up. Patients who underwent postoperative radiotherapy tended to exhibit reduced mouth opening. The pouch-type flap configuration represents a useful reconstructive option for treating extensive retromolar defects through 3-dimensional reconstruction and addressing postoperative trismus and cheek depression.
Modern hospitals are increasingly defined by their ability to manage undifferentiated, complex acute medical demand rather than elective programmes or specialist services. The Midland Metropolitan University Hospital (MMUH) opened in October 2024, and is one of the first major UK acute hospitals deliberately designed around an acute internal medicine (AIM)-centred model. This article describes the clinically led design principles underpinning MMUH, how AIM was positioned as the operational core of the hospital, and reports early results demonstrating improvements in flow, bed occupancy, emergency access, workforce resilience, mortality and infection control. Despite consolidating two legacy hospital sites into a single building and opening with 100 fewer acute beds, MMUH has delivered measurable operational improvements within months of opening. These figures provide a compelling blueprint for the New Hospital Programme (NHP), demonstrating how embedding AIM at the architectural and strategic heart of hospital design can enhance safety, efficiency and patient outcomes. These findings represent early outcomes, and longer-term follow-up is required to assess the durability, sustainability and generalisability of the observed improvements.
Voluntary muscle contraction is triggered by the neurotransmitter acetylcholine binding its receptors on the postsynaptic membrane of the neuromuscular junction, opening ion channels that allow cation influx and initiate depolarization1-3. Mutations in muscle acetylcholine receptors disrupt this process by either impairing (fast-channel) or prolonging (slow-channel) channel openings1,4. These defects cause congenital myasthenic syndromes (CMS), characterized by severe muscle weakness that is often present at birth and, in some cases, progresses to paralysis and death5,6. The structural mechanisms underlying these pathogenic defects and their pharmacological correction remain unknown. Here, using cryogenic electron microscopy, chemical biology and electrophysiology, we determined the structures and functional consequences of representative CMS mutant receptors with and without drugs. In fast-channel disease-associated mutants, we discovered a cryptic allosteric site targeted by positive modulators that restore gating in a mutation-specific manner. In receptor mutants associated with slow-channel disease, quinidine, fluoxetine and reboxetine act as pore blockers; notably, the antidepressant reboxetine selectively blocks desensitized receptors in a mutation-independent fashion, suggesting repurposing potential. Mechanistically, fast-channel mutations uncouple agonist binding from gating, whereas slow-channel mutations stabilize an abnormally widened, desensitized-like pore. These findings reveal unifying principles of CMS pathogenesis and provide a framework for precision therapies.
During the floral evolution of Delphinium (Ranunculaceae), the lineage leading to speciose subgenera of Delphinastrum/Oligophyllon gained a novel trait of asymmetric bending in their lateral petals, which further reinforced the highly specialized petal movement, mirrored helical rotation, during their flower opening. Our previous study in Delphinium anthriscifolium identified DeanLATE MERISTEM IDENTITY1 (DeanLMI1) as a key regulator, but its broad expression suggests that additional co-regulators are required for specifying its function. Here, by screening the transcriptome data from DeanLMI1-silenced lateral petals, together with detailed morphological, functional and interaction studies, we aim to uncover the DeanLMI1-mediated module underlying the evolution of lateral petal asymmetric bending in Delphinium. We identified a class II TCP (TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTORS) family gene, DeanTCP4-1, whose expression overlaps with DeanLMI1 at the hinge region of the lateral petals, where the asymmetric bending initiates. Silencing DeanTCP4-1 alone or together with DeanLMI1 resulted in the loss of this trait. Such a function is supported by direct activation of DeanTCP4-1 by DeanLMI1 and their protein-protein interaction. This work highlights that a functional module formed by LMI1 and TCP4 homologs is required for the evolution of lateral petal asymmetric bending in Delphinium, and also provides insights into the molecular mechanisms underlying diverse flower opening and plant movements.
Drought stress is a major limitation to sustainable floriculture in arid regions, severely affecting plant growth and flower quality. To mitigate these effects, this study evaluated foliar application of salicylic acid (SA; 300 ppm) applied alone and in combination with indole-3-acetic acid (IAA; 200 ppm), ascorbic acid (AA; 300 ppm), and chitosan (CS; 300 ppm) on the growth, photosynthetic performance, and antioxidant defense of Polianthes tuberosa L. under graded drought conditions [90%, 70%, and 40% water-holding capacity (WHC)]. The experiment was arranged in a factorial randomized complete block design with five replications. Drought stress was imposed for 8 weeks until first floret opening, while foliar treatments were applied four times (25, 40, 55, and 70 days after planting) starting at the three-leaf stage (BBCH 13). Results showed that severe drought (40% WHC) stress significantly reduced shoot biomass by ~ 60%, root biomass by 65-70%, and root surface area by ~ 45%, compared with well-watered conditions (90% WHC), indicating strong growth inhibition. A significant drought × PGR interaction confirmed that treatment responses were stress dependent. Among treatments, SA + IAA most effectively improved growth, biomass accumulation, and reproductive traits across drought levels, whereas SA + CS improved plant water status and reduced electrolyte leakage. In contrast, SA + AA better maintained chlorophyll fluorescence parameters and photosynthetic efficiency under drought stress. These responses were supported by increased antioxidant enzyme activity (SOD, CAT, POD), higher phenolic content, and soluble proteins, contributing to improved drought tolerance. Overall, SA-based combinations improved drought tolerance in a trait-specific manner, with SA + IAA promoting growth, SA + AA supporting photosynthetic performance, and SA + CS improving water status and membrane stability under water-limited conditions. These findings suggest that SA-based growth regulator combinations may enhance drought resilience and sustain growth in Polianthes tuberosa under water-limited conditions.
Aminobacter niigataensis MSH1 is a candidate for bioaugmentation of sand filters in drinking water treatment plants (DWTP), as it mineralizes the ubiquitous groundwater micropollutant 2,6-dichlorobenzamide (BAM). The DWTP sand filter isolate Piscinibacter sp. K169 improves BAM mineralization by MSH1 in an apparent accidental mutual cooperation, and co-inoculation of the organism was proposed to assist bioaugmentation with MSH1. In this study, we questioned whether this accidental mutual positive interaction extends to four other pesticide catabolic bacterial strains of the same or a different genus of MSH1, and examined the longevity of the cooperation. Negative interactions were never observed in either direction. As observed for BAM mineralization by MSH1, K169 stimulated BAM mineralization by A. niigataensis LG1 and 2,4-D mineralization by Cupriavidus pinatubonensis JMP134 without affecting the cell density of the catabolic strains. Linuron mineralization by Variovorax sp. SRS16 and carbofuran mineralization by Novosphingobium sp. KN65.2 were not affected. In the other direction, growth of K169 was stimulated by all pesticide catabolic strains except JMP134, indicating a common underlying mechanism. After 2 weeks, the beneficial effects of K169 on MSH1, LG1, and JMP134 functionality diminished or even reversed, likely because of organic carbon depletion. In contrast, cell densities of K169 in all dual-species systems remained higher than in the K169 monoculture system. This study extends our knowledge on accidental interactions and the beneficial effect of a sand filter isolate toward other pesticide degraders, opening doors for Piscinibacter sp. K169-assisted bioaugmentation of other/multiple pesticide degraders in DWTPs. Sand‑filter bioaugmentation with the BAM‑catabolic Aminobacter niigataensis MSH1 represents an advanced strategy for removing BAM from groundwater in drinking water treatment; however, prior studies indicate that efficacy lasts only for 1-2 weeks. Piscinibacter sp. K169, an isolate from drinking‑water sand filters, supports mineralization of BAM by MSH1 through accidental mutual cooperation, and co‑inoculation with K169 was suggested as an innovation to improve MSH1 bioaugmentation. We show that K169 promotes mineralization of OMPs by other bacteria and, hence, that the K169-degrader cooperation can be extended to support removal of other or even multiple OMPs. Benefits declined over time, likely due to nutrient depletion, making nutrient management a requirement for maintaining the cooperation. To the best of our knowledge, this is the first study to examine specificity in accidental microbial cooperation, especially in a bioaugmentation context of water treatment. It is relevant both to a fundamental understanding of accidental microbial interactions and to applications in water treatment.
To present the stepwise plication of abdominal mesh (SPAM) as a standardized dynamic closure technique that combines mesh-mediated fascial traction with negative pressure wound therapy for gradual abdominal wall approximation. In this technical report, we present SPAM for progressive closure of peritoneostomy with excessive abdominal wall retraction. It involves a central mesh incision followed by progressive tightening via hemostatic clamp rotation (similar to opening a can with a key), without full-thickness mesh cut. The mesh is secured with continuous suture and covered with a non-commercial negative pressure system. Cycles are repeated every 48-72 hours until fascial closure. SPAM was applied in four patients: three successful cases (52-year-old male with rectal perforation, 36-year-old female post-Hartmann evisceration, 63-year-old female with gastrojejunal anastomosis leak) achieved primary fascial closure in a median of 10 days, with well-tolerated traction, no enteroatmospheric fistula, or incisional hernia. In one failure (59-year-old male with gastrojejunal leak post-laparoscopic gastrectomy), bleeding occurred during traction (controlled surgically), yet the technique was discontinued due to progressive clinical deterioration. SPAM offers a practical, standardized, reproducible approach to delayed fascial closure, particularly in resource-limited settings, enabling controlled progressive approximation without mesh resection.
The widespread use of organophosphate pesticides (OPs) critically endangers food safety and environmental health, necessitating highly sensitive detection strategies. Herein, we report a d-band modulated Au@RuPt core-shell nanozyme for ultrasensitive OP detection via an oxygen reduction reaction (ORR) inhibition mechanism. The Au@RuPt nanodots (RuPt shell ∼1.02 nm on Au core ∼3.08 nm) exhibit enhanced ORR activity (Tafel slope: 49.89 mV dec-1) with a dominant four-electron pathway. Mechanistic studies reveal that Ru incorporation upshifts the d-band center, promoting thiocholine (TCh) chemisorption and consequent ORR poisoning. The biosensing mechanism relies on TCh-induced ORR inhibition and its recovery upon OP-mediated acetylcholinesterase inactivation, enabling a "signal-on" readout. The sensor exhibits a detection limit of 0.0264 ng mL-1 toward phoxim, alongside excellent specificity, reproducibility (RSD < 1.62%), stability (>94.6% after 30 days), and real-sample recoveries (96.3-104.6%). It also enables in situ pesticide monitoring on plant leaves and AChE activity evaluation with IC50 quantification for multiple OPs. This work establishes an alloy nanozyme platform for ORR-based electrochemical biosensing, opening new avenues for point-of-need applications in agricultural safety, toxicology, and clinical diagnostics.
Single-particle techniques have the potential to measure the heterogeneous dynamics at the nanoscale within reaction mixtures. However, new tools are needed to gain insight into the molecular structure of evolving chemical systems at the single-particle level. Here, a single-particle method for measuring the density and mass of freely diffusing polymer nanoparticles is introduced and applied to the ring-opening metathesis polymerization of norbornene. Using 3D single-molecule active real-time tracking, growing polymer nanoparticles are tracked in situ, enabling simultaneous real-time measurement of both particle size and particle density. Particle density is extracted from the descent velocity of growing nanoparticles, giving insight into particle composition at the single-particle level. Using this technique, it is found that polynorbornene nanoparticles have a density of 850 ± 30 kg/m3, validated through control measurements on polystyrene beads. Density and size analysis indicate each nanoparticle contains ∼3.5 × 109 densely packed monomers, rather than loosely packed polymer chains. Simulations show that the accuracy of this method depends on particle size, the distance traveled before contact with the coverslip, solvent properties, and the number of trajectories. Overall, this paper presents a technique that enables in situ characterization of the density and mass of individual growing polymer nanoparticles.
Post-myocardial infarction (post-MI) depression is a common clinical complication affecting approximately 29-40% of post-MI patients, whose pathological mechanism remains incompletely understood. While Shuangxinfang (Psycho-cardiology formula, PCF) has demonstrated efficacy in treating post-MI depression, its specific underlying mechanism of action remains poorly understood. This study seeks to elucidate the common pathological mechanisms underlying myocardial infarction and depression, as well as the therapeutic pathway by which PCF exerts its effects, through an integrated approach combining transcriptomics, cellular experiments, and animal studies. Transcriptomic analysis was employed to identify the potential molecular pathways. Cellular models employing H9C2 cardiomyocytes and astrocytes were established and subjected to hypoxia/reoxygenation intervention and S100A9 overexpression plasmid transfection, respectively. A rat model of post-MI depression was established. To validate the key findings, the following analytical methods were employed in the present study: real-time quantitative PCR (qRT-PCR), Western blotting, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), colorimetric assays, and transmission electron microscopy (TEM). Transcriptomic analysis revealed that PCF potentially targets S100A9, the NLRP3 inflammasome, and mitochondrial dysfunction. Both in vivo and in vitro experiments confirmed that PCF primarily inhibits S100A9, thereby reducing S100A9/NLRP3 inflammatory pathway factors (S100A9, NLRP3, Caspase-1, IL-18, and IL-1β) and ameliorating mitochondrial energy metabolism. These effects included enhanced activity of mitochondrial complexes I-V, elevated mitochondrial membrane potential, decreased mitochondrial permeability transition pore opening, improved mitochondrial ultrastructure, facilitated ADP-to-ATP conversion, and ultimately enhanced ATP production. S100A9/NLRP3 inflammasome-mediated mitochondrial energetic dysfunction may represent the common pathological mechanism linking post-MI cardiac dysfunction and depression, while simultaneously serving as a therapeutic pathway through which PCF exerts its therapeutic effects.
State regulations governing opioid treatment programs (OTPs) vary widely in their restrictiveness, yet how state policies relate to the availability of services offered within OTPs remains understudied. In this study, we compare the availability of medication for opioid use disorder (MOUD) options, psychosocial services, and housing supports across OTPs operating in states with different levels of OTP policy restrictions. We conducted a cross-sectional study of 1501 opioid treatment programs (OTPs) in the United States. Exposures included 11 state-level OTP policies that impose legal or administrative barriers to opening or operating OTPs or to patients' receipt of care (e.g., pharmacy licensure requirements, zoning restrictions, government identification requirements, and administrative discharge for positive drug screenings). Data on OTP service offerings-including buprenorphine, naltrexone, all three medications for opioid use disorder, mental health services, contingency management, trauma-informed counseling, and housing services-and organizational characteristics were obtained from the 2023 Mental Health and Addiction Treatment Tracking Repository, a national longitudinal database of licensed substance use disorder treatment facilities. These data were linked to a previously developed state policy typology using latent class analysis, which categorized states as having low or high OTP restrictiveness. Regression models adjusted for state- and organizational-level characteristics and accounted for clustering within states. In descriptive analyses, OTPs in highly restrictive states were significantly less likely (p < 0.05) to offer all three MOUDs and behavioral health services, including mental health services, trauma-informed counseling, and contingency management, compared with OTPs in low-restrictiveness states. In adjusted Poisson regression models, facilities in highly restrictive states were significantly less likely to offer naltrexone (ARR: 0.73; 95% CI: 0.54-0.97) and all three MOUDs (ARR: 0.70; 95% CI: 0.53-0.92). Given that OTPs are the only facilities in which methadone can be legally dispensed, these facilities are a critical point of access for individuals in need of evidence-based OUD treatment. However, our findings suggest that states that place additional restrictions on OTPs also offer less services within their OTPs.
Transverse maxillary deficiency is nearly universal in patients with cleft lip and/or palate (CLP) and represents a major determinant of occlusal function, surgical accessibility, and long-term stability. Despite established principles of rapid maxillary expansion and secondary alveolar bone grafting (SABG), considerable variability persists in appliance selection, timing, and sequencing of orthodontic and surgical interventions. To develop a standardized, evidence-informed clinical algorithm for the management of transverse discrepancies in non-syndromic CLP patients, integrating orthodontic biomechanics with surgical timing considerations. This study presents an algorithm-development framework based on structured clinical reasoning and synthesis of contemporary cleft care principles. Key variables incorporated into the decision pathway included cleft phenotype, presence of anterior segment collapse, type of posterior crossbite (relative versus absolute), dental development stage, and readiness criteria for SABG. Appliance selection (Hyrax, fan-type expander, differential opening expander), rate of activation, retention strategy, and post-graft orthodontic timing were systematically organized into a stepwise protocol designed for reproducibility across multidisciplinary cleft teams. This work is principally a structured review and synthesis of the existing literature, designed to organize established knowledge into an actionable clinical framework; no novel clinical concepts or techniques are introduced for the first time. The presented algorithm provides a structured, clinically applicable framework to harmonize orthodontic and surgical management of transverse discrepancies in CLP patients, aiming to reduce treatment variability, enhance interdisciplinary coordination, and improve graft-related and occlusal outcomes.