Sacubitril/valsartan reversal of left ventricular remodeling is associated with improved hemodynamics in resistant hypertension.

BACKGROUND: Sacubitril/valsartan (S/V) has been shown to be an effective antihypertensive drug combination. However, its therapeutic effects on blood pressure (BP), hemodynamics, and left ventricular (LV) remodeling in resistant hypertension (RHTN) remain unclear. METHODS: Eighty-six patients completed this self-control study, during which olmesartan was administered within the first 8 weeks (phase 1), followed by S/V within the second 8 weeks (phase 2), with nifedipine and hydrochlorothiazide taken as background medications. Office BP, echocardiography, and hemodynamics assessment using impedance cardiography were performed at baseline and at the eighth and sixteenth weeks. RESULTS: The reduction in office BP was larger in phase 2 than in phase 1 (19.59/11.66 mmHg vs. 2.88/1.15 mmHg). Furthermore, the treatment in phase 2 provided greater reductions in systemic vascular resistance index (SVRI) and thoracic blood saturation ratio (TBR), with differences between the two phases of -226.59 (-1212.80 to 509.55) dyn·s/cm5/m2 and -0.02 (-0.04 to 0.02). Switching from olmesartan to S/V also significantly reduced E/E', LV mass index, LV end-diastolic volume index, and LV end-systolic volume index (all P < 0.05). Decreases in arterial stiffness, SVRI, and TBR were correlated with changes in indicators of LV remodeling (all P < 0.05). This correlation persisted even after adjusting for confounders including changes in BP. CONCLUSIONS: Switching from olmesartan to S/V effectively lowered BP and reversed ventricular remodeling in RHTN. In addition, hemodynamic improvement was also observed. Changes in hemodynamics played an important role in reversing LV remodeling of S/V, and were independent of its antihypertensive effect.

Exploring the Multifaceted Landscape of Pediatric Obstructive Sleep Apnea: Insights into Prevalence, Severity, and Coexisting Conditions.

Background: Pediatric obstructive sleep apnea (OSA) is a multifaceted disorder marked by recurrent upper airway obstruction during sleep, often coexisting with various medical conditions. This study, aimed to comprehensively analyze the Multifaceted Landscape of Pediatric Insights into Prevalence, Severity, and Coexisting Conditions. With a sample of 1928 participants, our study sought to determine the prevalence, severity, and associations between OSA and diverse conditions. Methods: Conducted retrospectively from February 2019 to April 2023, the study included pediatric patients. Data were collected through electronic health records, involving clinical assessments, medical histories, and diagnostic tests to establish OSA and coexisting condition diagnoses. Relationships between sleep parameters, apnea types, and severity indices were evaluated. Results: High OSA prevalence was evident across age groups, with severity peaking between 3 to 12 years. Among the participants, coexisting conditions included allergic rhinitis (59.6%), tonsillar hypertrophy (49.7%), adenoid hypertrophy (28.4%), and obesity (15.3%). Analysis revealed intriguing relationships between different sleep parameters and apnea types. Notable associations were observed between Obstructive Apnea (OA) and Central Apnea (CA), and Mixed Apnea (MA) displayed associations with both OA and CA. Hypopnea correlated directly with the Apnea-Hypopnea Index (AHI), reflecting its role in OSA severity. Conclusion: This study provides a comprehensive understanding of the intricate dynamics between pediatric OSA and coexisting conditions. The prevalence of OSA and its coexistence with various conditions underscore the need for comprehensive evaluation and management strategies. By revealing associations between different sleep parameters and apnea types, the study emphasizes the complexity of OSA diagnosis and management. These findings hold the potential to enhance clinical approaches, ultimately leading to improved care and outcomes for affected children.

Case report: A novel splice-site mutation of MTX2 gene caused mandibuloacral dysplasia progeroid syndrome: the first report from China and literature review.

Background: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported. Methods: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date. Results: The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades. Conclusion: This is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

Alexithymia and negative emotions among nursing students: a moderated mediation model.

Nursing students, who comprise a high percentage of China's college students, experience many psychological problems; however, few studies explored the mechanisms underlying these problems. This cross-sectional study explored the relationships and mechanisms of depression, anxiety, stress, and narrative disorders in senior nursing students. Questionnaires were administered to 380 senior nursing students in Hubei Province using the Sociodemographic Questionnaire, Toronto Alexithymia-20 Scale, Perceived Social Support Scale, 10-Item Connor-Davidson Resilience Scale, and Depression-Anxiety-Stress Scale. After controlling for sociodemographic variables, Hayes' PROCESS macros were used to test how psychological resilience moderates the relationships among narrative disorders, negative affect, and perceived social support. Bootstrap confidence intervals tested for indirect effects. Correlation analyses revealed that alexithymia was correlated significantly positively with depression-anxiety-stress (r = 0.57, 0.56, and 0.58, resp.) and significantly negatively with perceived social support (r = 0-0.46). Psychological resilience was correlated significantly negatively with alexithymia (r=-0.39) and depression-anxiety-stress (r=-0.31, -0.30, and-0.32, resp.) but significantly positively with perceived social support(r = 0.50). Perceived social support was correlated significantly negatively with depression-anxiety-stress (r=-0.33, -0.34, and - 0.42 resp.). Stress was correlated significantly positively with anxiety and depression (r = 0.81 and 0.77, resp.). Psychological resilience was a partial mediator between depression and dysphoria (ß=-0.08, p < 0.05). Dysphoria directly predicted anxiety (ß = 0.31) and stress (ß = 0.37); moreover,alexithymia predicted depression not only directly but also through the mediating effect of psychological resilience. Therefore, educators and clinical administrators must promote and recognise negative emotions among nursing students to help ensure the nursing workforce's stability.

Nanosecond Laser Fabrication of Novel Micro-/Nanostructured Metal Surfaces: A Dual-Functional Supersurface Combining Antireflectivity and Superhydrophobic Properties.

The research and applications in the field of micro/nano surface manufacturing are progressively shifting their focus toward multifunctional surfaces. In practical applications, objects often need to operate under demanding environmental conditions, and single-function surfaces have inherent limitations in terms of performance, adaptability, and longevity. In this paper, a micro-/nanolayered structural strategy with dual functions of ultrahigh antireflective properties and superhydrophobicity was created on the surface of titanium alloy by using nanosecond pulsed laser processing, and two structural modes of periodic honeycomb and lattice with controllable shapes were designed. In addition, the morphology and formation mechanism of multilevel micro-/nanostructures were investigated in depth, combining laser texturization and silanization of substrate microstructures. The effects of the micro-/nanostructured morphology on the reflection and wettability properties were evaluated with different pulse widths and lateral overlap index. This study also demonstrated that water droplets exhibit excellent bouncing and rolling behavior on superhydrophobic surfaces, further verifying the excellent hydrophobic properties of the prepared samples. Furthermore, in addressing the challenges of susceptibility to dust contamination and performance degradation in extreme environments associated with antireflective surfaces, a series of durability and mechanical stability tests were conducted on controllability periodic micro-/nanostructured surfaces. Successfully meeting this challenge will open up great potential and opportunities for significant improvements in equipment performance and stable operation under extreme operating conditions.

Controllable Circularly Polarized Luminescence with High Dissymmetry Factor via Co-Assembly of Achiral Dyes in Liquid Crystal Polymer Films.

Circularly polarized luminescence (CPL) materials are highly demanded due to their great potential in optoelectronic and chiroptical elements. However, the preparation of CPL films with high luminescence dissymmetry factors (glum ) remains a formidable task, which impedes their practical application in film-based devices. Herein, a facile strategy to prepare solid CPL film with a high glum through exogenous chiral induction and amplification of liquid crystal polymers is proposed. Amplification and reversion of the CPL appear when the films are annealed at the chiral nematic liquid crystalline temperature and the maximal glum up to 0.30 due to the enhancement of selective reflection. Thermal annealing treatment at different liquid crystalline states facilitates the formation of the chiral liquid phase and adjusts the circularly polarized emission. This work not only provides a straightforward and versatile platform to construct organic films capable of exhibiting strong circularly polarized emission but also is helpful in understanding the exact mechanism for the liquid crystal enhancement of CPL performance.

Fibronectin Connecting Cell Sheet Based on Click Chemistry for Wound Repair.

As a living repair material, cell sheet exhibits significant potential in wound repair. Nonetheless, wound healing is a complicated and protracted process that necessitates specific repair functions at each stage, including hemostasis and antibacterial activity. In this work, on the basis of harvesting the cell sheet via a photothermal response strategy, a fibronectin attached cell sheet (FACS) is prepared to enhance its wound repair capability. For this purpose, the azide group (N3 ) is initially tagged onto the cell surface through metabolic glycoengineering of unnatural sugars, and then the conjugate (DBCO-fibronectin) comprises of the dibenzocyclooctyne (DBCO) and fibronectin with multiple wound repair functions is linked to N3 using click chemistry. Biological evaluations following this demonstrates that the FACS preparation exhibits excellent biocompatibility, and the fibronectin modification enhances the capacity for cell proliferation and migration. Moreover, in vivo wound healing experiment confirms the reparative efficacy of FACS. It not only has a wound closure rate 1.46 times that of a conventional cell sheet but also reduces inflammatory cell infiltration, promotes hair follicle and blood vessel regeneration, and encourages collagen deposition. This strategy holds enormous clinical potential and paves the way for advanced functional modifications of cell sheets.

Formation and modulation of multi-pulse femtosecond laser-induced periodic surface structures by electromagnetic and partial differential equation simulations.

In order to demonstrate the formation of laser-induced periodic surface structures (LIPSS), simulations were performed to investigate the effect of multiple femtosecond laser pulses with different laser energy densities on a Ti6Al4V surface. In this work, a set of partial differential equations calculating the electron and lattice temperature variations, followed by coupling with an electric field, is used to analyze the evolution of the periodic surface structure induced by the interaction of the femtosecond laser with the material. As the number of pulses increases, the surface structure of the material changes from none to produce LIPSS structure and from low spatial frequency LIPSS (LSFL) structure to high spatial frequency LIPSS (HSFL) structure. In order to compare the results, single-point laser scanning ablation experiments were carried out at femtosecond laser energy. The experimental results are consistent with the simulation results.

Machine-Learning-Enabled Framework in Engineering Plastics Discovery: A Case Study of Designing Polyimides with Desired Glass-Transition Temperature.

Great and continuous efforts have been made to discover high-performance engineering plastics with specific properties to replace traditional engineering materials in many fields. The utilization of machine learning (ML) has brought more opportunities for the discovery of high-performing engineering plastics. However, hindered by either the relatively small database or a lack of accurate structure descriptors with clear physical and chemical meanings relating to polymer properties, the current ML studies show some flaws in the accuracy and efficiency in polymer development. Herein, we collected a dataset of 878 polyimides (PI), one of the best engineering plastics, with experimentally measured glass-transition temperature (Tg) values, and developed a rapid and accurate ML approach to design PI candidates with the desired Tg value. After the conversion from PI structures into "mechanically identifiable" SMILES (Simplified molecular input line entry system) language, the eight most critical descriptors were ultimately obtained by multiple analysis methods. The physiochemical meaning of the key descriptors was further analyzed carefully to translate the implicit "machine language" to chemical knowledge. The artificial neural network (ANN)-based model gave the most accurate results with a root-mean-square error of ∼11 K among the studied ML methods. More importantly, three potential PI candidates with desired Tg (DPIs) were designed according to the chemical insight of the key descriptors, which were then verified by experiments. The experimental and predicted Tg values of DPIs have an acceptable average deviation of ca. 3.66%. This accuracy has reached the level of the traditional molecular simulation, but the time consumption and hold-up computing resource are tremendously reduced. Furthermore, the current ML approach could offer a scalable and adaptable framework in future engineer plastics innovation.

Comparison of Homo-Polyimide Films Derived from Two Isomeric Bis-Benzimidazole Diamines.

Heteroaromatic polyimides (PIs) containing benzimidazole have attracted tremendous attention due to their positive impact on the properties of PIs. Some research on PIs containing 4,4'-[5,5'-bi-1H-benzimidazole]-2,2'-diylbis-benzenamine (4-AB) has been reported. However, reports are lacking on homo-polyimides (homo-PIs) containing 3,3'-[5,5'-bi-1H-benzimidazole]-2,2'-diylbis-benzenamine (3-AB), which is one of the isomers of 4-AB. In this paper, the influence of amino groups' positions on the performance of homo-PIs was investigated. It was found that the net charge of the amine N group in 4-AB was lower than that of 3-AB, resulting in higher reactivity of 4-AB. Consequently, PIs containing 4-AB displayed better mechanical performance. Molecular simulation confirmed that 3-AB and its corresponding PI chain exhibited distorted conformation, leading to the PI films containing 3-AB having a lighter color. In addition, the 3-AB structure was calculated to have higher rotational energy compared to 4-AB, resulting in a higher glass transition temperature (Tg) in PIs prepared from 3-AB. On the other hand, PIs containing 4-AB exhibited a higher level of molecular linearity, leading to a lower coefficient of thermal expansion (CTE) compared to PIs prepared from 3-AB. Furthermore, all PIs showed higher thermal stability with a 5% weight loss temperature above 530 °C and Tg higher than 400 °C.

The rise and fall of acute rheumatic fever and rheumatic heart disease: a mini review.

Introduction: The incidences of acute rheumatic fever (ARF) and rheumatic heart disease (RHD), which were leading causes of death in children in the 1920s, have decreased substantially. Considering the recent resurgence of scarlet fever and increased incidence of streptococcal pharyngitis in children, an investigation of the current status of ARF and RHD may be worthwhile. Objective: To summarize the prevalence trends, pathogenic factors, and prevention strategies for ARF and RHD in children. Methods: A selective search of literature published between January 1920 and February 2023 was done in PubMed, using the terms "acute rheumatic fever", "rheumatic heart disease", "group A Streptococcus", "pharyngitis", "pharyngeal tonsillitis", "scarlet fever", "impetigo", "obstructive sleep apnea syndrome" and "child". Results: Overcrowded homes and inadequate sanitation led to recurrent group A streptococcal infection, and the causal relationship between group A streptococcal infection and ARF/RHD was well established. Streptococcal infectious diseases, such as group A streptococcal pharyngeal tonsillitis, SF, impetigo, and obstructive sleep apnea syndrome, were associated with the occurrence of ARF and RHD. ARF and RHD were still prevalent in young people of developing countries and economically poor populations of high-income countries. Universal disease registration systems were critical to locating disease outbreaks, tracking disease transmission, and identifying high-risk populations. Four-level prevention strategies were effective in reducing the incidence and mortality of ARF and RHD. Conclusions: Registry and preventive measures for ARF and RHD should be strengthened in areas of dense population; poor sanitation; resurgence of SF; and high incidence of streptococcal pharyngitis, impetigo, and obstructive sleep apnea syndrome.

Baseline Data and HLA Alleles and Haplotypes Diversity and Panel Reactive Antibody in Kidney Transplant Candidates in Southwest China.

BACKGROUND: To investigate the baseline data characteristic, human leukocyte antigen (HLA) polymorphisms, and panel reactive antibody (PRA) in end-stage kidney disease (ESKD) patients awaiting kidney transplantation in Southwest China. METHODS: HLA genotyping was performed using the real-time PCR sequence-specific primer. PRA was detected by enzyme-linked immunosorbent assay. The patients' medical records were extracted from the hospital information database. RESULTS: A total of 281 kidney transplant candidates with ESKD were analyzed. The average age was 35.7 ± 13.8 years. There were 61.6% patients had hypertension, 40.2% patients had dialysis ≥ 3 times per week, 47.3% patients had moderate or severe anemia, 30.2% patients with albumin < 35 g/L, 49.1% patients had serum ferritin < 200 ng/mL, 40.5% patients had serum calcium in target range (2.23 - 2.80 mmol/L), 43.4% patients had serum phosphate in target range (1.45 - 2.10 mmol/L), and 93.6% patients with parathyroid hormone > 88.00 pg/mL. In total, 15 HLA-A, 28 HLA-B, 15 HLA-DRB1, and 8 HLA-DQB1 allelic groups were identified. The most frequent alleles for each locus were HLA-A*02 (33.63%), HLA-B*46 (14.41%), HLA-DRB1*15 (21.89%), and HLA-DQB1*05 (39.50%). The most frequent haplotypes were HLA-A*33-B*58-DRB1*17-DQB1*02. A total of 9.60% of patients tested positive for PRAs - Class I or Class II. CONCLUSIONS: The data from this study provide some new insights into baseline data, the distribution of HLA polymorphisms, and PRA results in the population of Southwest China. This is of great significance in this region, and indeed in the country as a whole, in comparison with other populations and in the process of organ transplant allocation.

DFML: Dynamic Federated Meta-Learning for Rare Disease Prediction.

Millions of patients suffer from rare diseases around the world. However, the samples of rare diseases are much smaller than those of common diseases. Hospitals are usually reluctant to share patient information for data fusion due to the sensitivity of medical data. These challenges make it difficult for traditional AI models to extract rare disease features for disease prediction. In this paper, we propose a Dynamic Federated Meta-Learning (DFML) approach to improve rare disease prediction. We design an Inaccuracy-Focused Meta-Learning (IFML) approach that dynamically adjusts the attention to different tasks according to the accuracy of base learners. Additionally, a dynamic weight-based fusion strategy is proposed to further improve federated learning, which dynamically selects clients based on the accuracy of each local model. Experiments on two public datasets show that our approach outperforms the original federated meta-learning algorithm in accuracy and speed with as few as five shots. The average prediction accuracy of the proposed model is improved by 13.28% compared with each hospital's local model.

Group A Streptococcus Is Still at Large.

Group A Streptococcus (GAS) is a major human pathogen that can cause diseases, ranging from mild to severe systemic and invasive diseases [...].

Precise Preparation of a Multilayer Tubular Cell Sheet with Well-Aligned Cells in Different Layers to Simulate Native Arteries.

Compared with artificial vascular grafts, bottom-up tubular cell sheets (TCSs) without scaffolds have shown promise for patients with cardiovascular disease. However, TCS therapy also faces the challenges of lengthy maturation time, elaborate operation, and weak mechanical strength. In this work, a structured small-diameter vascular graft (SDVG), consisting of three layers of TCSs, with different cell types and arrangements, was fabricated using layer-by-layer assembly of naturally formed TCSs and further cell culture. To this end, a surface-patterned collagen-coated cylindrical substrate was designed for the efficient harvesting of naturally formed and well-aligned TCSs. The patterned collagen (type I) layer facilitated the adhesion and orientation of cells, and a continuous tubular cell monolayer was naturally formed after approximately 4 days in cell culture. Biocompatible near-infrared (NIR) light was used to trigger the photothermal phase transition of the collagen coated on the cylindrical substrate to dissociate the collagen layer. As a result, an intact TCS could be harvested within a few minutes. These naturally formed and well-aligned TCSs exhibited outstanding free-standing performance without rugosity, facilitating their operability and practical application. A ring tensile test showed that orientation was critical for improving the mechanical properties of TCSs. The layer-by-layer assembly of SDVGs not only is easy to manipulate and has a short preparation time but also overcomes the bottleneck of forming a hierarchically structured vascular graft. This approach shows promise for repairing damaged blood vessels.

The relationship between psychiatric nurses' perceived organizational support and job burnout: Mediating role of psychological capital.

Background: Psychiatric nurses need to keep close contact with patients suffering from mental illness. Because of the special nature of their profession, there is an increasing incidence of job burnout among psychiatric nurses. Aim: This study examined the relationship between psychiatric nurses' perceived organizational support, job burnout, and psychological capital. It also investigated the mediating role of psychological capital in the relationship between their perceived organizational support and job burnout. Methods: A total of 916 psychiatric nurses were recruited from 6 grade-III mental facilities in Shandong Province using the stratified sampling approach. Their data were collected and examined using a general demographic data questionnaire, The Maslach Burnout Inventory, the Perceived Organizational Support Scale, and the Psychological Capital Questionnaire. Results: The total score of job burnout was 53.71 ± 16.37. Specifically, 73.69% of the nurses had moderate to severe emotional exhaustion, 76.75% had moderate to severe job burnout pertaining to depersonalization, and 98.80% had moderate to severe job burnout pertaining to personal accomplishment. Spearman's correlation analysis showed that both psychological capital (r = -0.35, p < 0.01) and perceived organizational support (r = -0.31, p < 0.01) were adversely related to job burnout. Additionally, psychological capital somewhat mediated the relationship between perceived organizational support and job burnout. Its mediating impact accounted for 33.20% of the overall effect. Conclusion: This study's participants had a moderate to severe level of job burnout. However, organizational support and psychological capital can be crucial in alleviating this problem among psychiatric nurses. Therefore, nursing managers and medical institutions should undertake timely and positive interventions to improve psychiatric nurses' mental health and prevent job burnout. While exploring the impact of organizational support and psychological capital on job burnout, future studies should consider other effective influencing factors, and the relationship between the different factors should be explored in depth. This would provide a basis for developing a job burnout prevention mechanism.

Drug self-framework delivery system-coated gold nanorods for multi-modal imaging and combination therapy for breast cancer.

Herein, we report a multifunctional nanodrug (Au NRs@DSFDSs NPs) by coating a drug self-framework delivery system (DSFDS) on Au NRs with absorption at 1300 nm via simple condensation polymerization, with the purpose of developing an efficient theranostic nanoagent with multi-modal imaging ability, and synergistic chemo-photothermal therapy (CT-PTT) for the monitoring and suppression of tumor growth. Thus, this strategy provides a new idea for the design of a multifunctional platform for the accurate and effective image-guided treatment of tumors.

CRISPR/Cas9-mediated gene editing of vacuolar ATPase subunit d mediates phytohormone biosynthesis and virus resistance in rice.

Vacuolar ATPases (V-ATPases) are proton pumps for proton translocation across membranes that utilize energy derived from ATP hydrolysis; OsV-ATPase subunit d (OsV-ATPase d) is part of an integral, membrane-embedded V0 complex in the V-ATPase complex. Whether OsV-ATPase d is involved in phytohormone biosynthesis and resistance in rice remains unknown. The knockout mutants of OsV-ATPase d in rice were generated using the CRISPR/Cas9 system, and mutation of OsV-ATPase d did not show any detrimental effect on plant growth or yield productivity. Transcriptomic results showed that OsV-ATPase d is probably involved in mediating the biosynthesis of plant hormones and resistance in rice. Compared to wild type, mutation of OsV-ATPase d significantly increased JA and ABA biosynthesis and resistance against Southern rice black-streaked dwarf virus (SRBSDV), but it decreased resistance against Rice stripe virus (RSV) in rice. The data presented in this study reveal that OsV-ATPase d mediates phytohormone biosynthesis and virus resistance in rice and can be selected as a potential target for resistance breeding in rice.

A whole-joint histopathologic grading system for murine knee osteoarthritis.

This study aims to develop a comprehensive and easily executable histopathologic grading scheme for murine knee osteoarthritis (OA) using specific scoring criteria for both cartilage and periarticular changes, which may overcome important limitations of the existing grading systems. The new grading scheme was developed based on mouse knee OA models with observation periods up to 24 months of age (spontaneous OA) or 24-week post-injury (posttraumatic OA). Semi-quantitative assessments of the histopathologic OA changes were applied to all four quadrants per femorotibial joint for 50 joints (200 quadrants) using specific scoring criteria rather than mild to severe grades. Scoring elements per quadrant were as follows: cartilage lesion (0-7), osteophyte (0-3), subchondral bone change (0-3), synovitis (0-3), and ectopic periarticular soft-tissue chondrogenesis and ossification (0-3). The new histopathologic grading scheme had high intra- and interobserver reproducibility (correlation coefficients r > 0.95) across experienced and novice observers. Sensitivity and reliability analyses confirmed the ability of the new scheme to detect minimal but significant OA progression (p < 0.01) within a 2-week interval and to accurately identify tissue- and quadrant-specific OA severity within the joints. In conclusion, this study presents the first whole-joint histopathologic grading scheme for murine knee OA that covers all-stage osteoarthritic changes in all major joint tissues, including periarticular soft-tissue ossification that is not included in any of the existing OA grading systems. This reproducible scheme is easy to execute and sensitive to minimal OA progression without using computer software, suitable for quick OA severity assessments of the entire femorotibial joint.