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Objective: To investigate whether the immunohistochemical results of two markers PMS2 and MSH6 (2-MMR) could replace the four markers MLH1, PMS2, MSH2 and MSH6 (4-MMR) to detect mismatch repair deficient (dMMR) cancers. Methods: A retrospective analysis was conducted with summary of immunohistochemical data from 7 867 cases of gastric cancer, colorectal cancer, endometrial cancer, and other diseases in the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, from March 2018 to March 2023. The consistency of 2-MMR and 4-MMR results was examined. Microsatellite instability (MSI) and next-generation sequencing (NGS) were performed in patients with specific phenotypes. Results: The Cohen κ values of 2-MMR and 4-MMR in gastric cancer, colorectal cancer, endometrial cancer and other diseases were 0.88, 0.99, 0.88 and 1.00, respectively. The overall consistency, sensitivity and specificity were 0.97, 99.6%, and 100.0%, respectively. Both 2-MMR and 4-MMR could detect the difference between various clinicopathological features. 24 (0.3%) of the 7 867 patients were found to have a special phenotype of MMR, and 6 of them were selected for MSI and NGS molecular testing. MSI analysis showed MSI-H in all cases, while NGS found that 5 of them had MMR-related gene mutations and 1 had POLE p.S297F mutation. Conclusions: Compared with 4-MMR, 2-MMR has high consistency, specificity and sensitivity. The cases with special phenotype only account for extremely low proportion. Therefore, 4-MMR may be replaced with 2-MMR in dMMR screening.

Osteoporosis, a significant bone disease predominantly affecting elderly and postmenopausal women, leads to increased bone fragility and fracture risk, presenting a major public health concern with substantial socioeconomic implications. This study investigated the therapeutic potential of Lactobacillus strains, known for their immunomodulatory properties, in an ovariectomy-induced osteoporosis mouse model. Among three tested strains Lactobacillus casei GKC1, Lactobacillus rhamnosus GKLC1, and Lactobacillus johnsonii GKJ2, GKC1 demonstrated superior efficacy in promoting osteogenesis-related gene expression, including alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). In ovariectomized mice (n = 8/group), both live and heat-inactivated GKC1 (57 mg/kg) and fermented GKC1 (1000 mg/kg) were administered orally for 28 days, with alendronate (2.5 mg/kg) serving as a positive control. The treatment significantly improved bone mineral density and femoral microstructure parameters compared to the ovariectomized control group. For the first time, heat-inactivated GKC1 exhibited superior anti-inflammatory effects through reduction of IL-17A and enhanced bone microstructural integrity, suggesting its potential as a safe and effective therapeutic agent for postmenopausal osteoporosis management. These findings provide compelling evidence for the development of postbiotic-based interventions in osteoporosis treatment, offering a promising alternative to conventional therapeutics., Competing Interests: Declaration of Competing interest Grape King Bio Ltd. provided salaries and research materials to Tsung-Ju Li, You-Shan Tsai, Ci-Sian Wang, Shih-Wei Lin, Yen-Lien Chen, and Chin-Chu Chen. The company had no other involvement in the research process. The remaining authors declare no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

This study is the first to explore the effects of the novel yellow pigment monascinol (Msol) from red mold rice (RMR) on reducing body fat and to compare its effects with those of monascin (MS) and ankaflavin (AK). In a high-fat diet-induced rat model, different doses of RMR fermented rice (RL, RM, RH) and purified Msol, MS, and AK were administered over an 8-week period. The results showed that all treatment groups significantly reduced body weight and fat mass. Msol, in particular, activated acetyl-CoA carboxylase (ACC), inhibiting fatty acid synthesis and reducing triglyceride accumulation. All treatments suppressed the differentiation of preadipocytes into mature adipocytes by inhibiting CCAAT/enhancer-binding proteins β (C/EBPβ) and C/EBPα, as well as peroxisome proliferator-activated receptor γ (PPARγ). In the liver, RL, RM, RH, MS, and AK enhanced the expression of AMP-activated protein kinase (AMPK), ACC, peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase-1α (CPT-1α), thereby promoting fatty acid metabolism. Additionally, RMR and its active components, MS and Msol, reduced body fat by modulating gut microbiota. These compounds significantly decreased the abundance of bacteria associated with fat storage, such as Oliverpabstia intestinalis, while increasing the abundance of bacteria linked to energy expenditure and lipid breakdown, such as Akkermansia muciniphila and Ruminococcus callidus. Moreover, MS and Msol upregulated proteins involved in fat degradation, such as UCP1, thereby enhancing fat burning and reducing fat accumulation. These regulatory effects suggest that Monascus and its components have potential in managing metabolic health and reducing obesity.

The growing popularity of three-dimensional (3D) food printing has highlighted the need for suitable printable materials. This study explores the impact of xanthan gum on octenyl succinic anhydride (OSA) starch-stabilized High Internal Phase Emulsions (HIPEs) for 3D food printing applications. Xanthan gum was added to increase the viscosity of the continuous phase, which helps to slow down the movement and reduce the collision of emulsion droplets. The enhanced rheological properties resulting from the addition of xanthan gum enabled the successful use of OSA-based HIPEs in 3D printing. The formulation containing 0.3 wt% xanthan gum produced accurately detailed printed scaffolds. Furthermore, the study demonstrates improved thermal stability of β-carotene when encapsulated within these HIPEs. These findings provide comprehensive guidelines for formulating starch HIPE inks, presenting a promising method for incorporating diverse hydrophobic molecules in 3D food printing applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hallux valgus (HV) is a complex, multiplanar deformity. In this study, we examined the interrelationships between various components of this deformity using weightbearing computed tomography (WBCT). We hypothesized that the severity of traditional axial plane deformities would correlate with malpositioning of the metatarsosesamoid complex, first-ray coronal rotational deformity, and malalignment of the hindfoot and midfoot. The findings may offer valuable insights for guiding the correction of HV deformities., Methods: Patients with an HV angle greater than 15 degrees who underwent WBCT were included. Traditional 2-dimensional parameters were semiautomatically assessed. Manual measurements included hindfoot and midfoot WBCT parameters, for example, foot and ankle offset, talar posterior and middle facet morphology, and forefoot arch angle. First-ray parameters, including first metatarsal rotation, sesamoid rotation angle, hallucal pronation angle, and sesamoid position, were measured using established methods. Patients were categorized by hindfoot moment arm values to evaluate hindfoot-forefoot relationships., Results: Sixty-eight feet (53 patients) were included. Manual measurements exhibited excellent interobserver reliability, with ICCs of 0.845 to 0.987 and a kappa coefficient of 0.899 for the sesamoid position. The mean HV angle was 27.4 ± 7.8 degrees, whereas the mean IM angle was 15.8 ± 3.5 degrees. Significant correlations were observed between the HV and intermetatarsal (IM) angles, with all metatarsosesamoid complex parameters and first-ray coronal plane rotational parameters distal to the metatarsal head. The axial and sagittal talar-first metatarsal angles correlated with the HV angle but not with the IM angle. Significant differences in the HV angle, sagittal first tarsal-metatarsal joint angle, and first metatarsal head rotation were observed between the hindfoot moment arm groups, as confirmed by post hoc analysis., Conclusion: The findings support our hypothesis, identifying significant correlations between metatarsosesamoid complex malposition, distal first-ray coronal pronation, and traditional axial plane deformities in HV. Some hindfoot-midfoot alignments correlated with the HV angle but not with the IM angle., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Cesar de Cesar Netto, MD, PhD, holds financial interests related to CurveBeam, Paragon 28, and Disior, including but not limited to equity, royalties, advisory roles, and consultancy fees. These interests have been managed in accordance with relevant regulations and Duke University’s policies. The author has entered into a conflict management plan with the relevant departments to ensure the objectivity of the research and the fairness of educational activities, as well as to uphold the reputation of Duke University. All other authors declare no conflicts of interest. Disclosure forms for all authors are available online.

Background: The Centers for Disease Control and Prevention (CDC) Environmental Justice Index Social-Environmental Ranking (EJI-SER) combines a Social Vulnerability Module (SV) with an Environmental Burden Module (EB) to characterize cumulative environmental and social burden at the census tract level. This analysis evaluates the association between EJI-SER and kidney outcomes in glomerular disease (GD) patients., Methods: Cure Glomerulopathy (CureGN) is an observational cohort study of adults and children with biopsy-proven GD. EJI-SER is a percentile ranking by census tract, with a higher score indicating a more severe burden. Associations between EJI-SER and its components with kidney failure (initiation of kidney replacement therapy, transplant, or two estimated glomerular filtration rates [eGFRs] <15ml/min/1.73m2) and longitudinal eGFR were tested using multivariable Cox regression and linear mixed models, respectively, adjusted for demographics, histologic diagnosis, eGFR and urine protein to creatinine ratio at enrollment, and time from biopsy to enrollment., Results: Among 1,149 participants with census tract data, the median (IQR) follow-up was 5.4 (3.0-7.0) years, the median (IQR) age at biopsy was 24 (10-48), and self-identified racial distribution was 5% Asian, 18% Black, and 70% White. Median (IQR) EJI-SER was 0.49 (0.26-0.75). EJI-SER scores in the lowest two quartiles were associated with a lower hazard of kidney failure compared to the highest quartile (adjusted HR [95% CI] 0.62 [0.36-1.08] and 0.43 [0.25-0.76] for EJI-SER 0-25% and >25-50% vs. >75%, respectively) and higher eGFR at enrolllment (adjusted mean 90.1 vs. 87.1 ml/min/1.73m2 for 0-25% vs. >75%, p=0.08)., Conclusion: As captured by EJI-SER, higher environmental and social burdens are associated with lower eGFR and a higher risk of kidney failure in the CureGN cohort. This first use of the EJI-SER in GD demonstrates the need for additional investigation into social drivers of disparities in GD and policies and resources that address these structural inequities., (Copyright © 2025 by the American Society of Nephrology.)

Organic photoelectrochemical transistor (OPECT) is an emerging technology studying photo-electric-biological recognition events. Here, this work reports the three-dimensional (3D) Z-scheme poly (1,4-diethynylbenzene) (pDEB)@Cu 2 O heterojunction as a high-efficacy photogating module and its application for OPECT bioassay. Specifically, 3D Z-scheme pDEB@Cu 2 O heterojunction enabled fast charge transport and ion diffusion in the system, achieving remarkable amplification capability with a current gain as high as ca. 9.6 × 10 3 . By linking with GOx-labeled sandwich immunorecognition, the impact of GOx-generated H 2 O 2 on the OPECT made possible the sensitive bioassay. Exemplified by carcinoembryonic antigen (CEA) as the model target, the OPECT device achieved a linear detection range spanning from 100 fg/mL to 100 ng/mL and coupled with a detection limit as low as 72 fg/mL. This work provided a generic and extensible platform for the designation of novel bioassay systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Since females grow faster in penaeid shrimp, all-female aquaculture was proposed. Environmental conditions in the Pacific white shrimp were not found to affect genetic sex determination (ZZ/ZW system). The androgenic gland-secreting insulin-like androgenic gland hormone is a key controlling factor in crustacean male differentiation. However, functional sex reversal (neo-male) in penaeid shrimp has not yet been achieved by manipulating the insulin-like androgenic gland hormone-sexual switch. Therefore, understanding the molecular mechanisms of gonadal differentiation may help build appropriate tools to generate neo-male for all-female breeding. This study describes the potential role of the novel penaeid-specific testicular zinc finger protein (pTZFP) in the gonads of Pacific white shrimp. First, pTZFP transcripts show a male-bias expression pattern in undifferentiated gonads, which is then exclusively expressed in the testis and absent or slightly expressed in the ovary and other tissues. Besides, the knockdown of pTZFP in undifferentiated males results in smaller testes but no sex reversal. Immunohistochemical staining of proliferating cell nuclear antigen further confirmed that the smaller testes in pTZFP-deficient males are due to the lower proliferating activity of spermatogonia. These data reveal that pTZFP may be involved in testicular development but have fewer effects on gonadal differentiation. Moreover, testicular pTZFP transcription levels were not reduced with estradiol-17β (E2) administration or AG excision. Therefore, our data suggest that pTZFP may regulate testicular development through downstream genes regulating spermatogonia proliferation. Moreover, our data provide an appropriate molecular marker for identifying the sex of undifferentiated gonads., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Breath biopsy is emerging as a rapid and non-invasive diagnostic tool that links exhaled chemical signatures with specific medical conditions. Despite its potential, clinical translation remains limited by the challenge of reliably detecting endogenous, disease-specific biomarkers in breath. Synthetic biomarkers represent an emerging paradigm for precision diagnostics such that they amplify activity-based biochemical signals associated with disease fingerprints. However, their adaptation to breath biopsy has been constrained by the limited availability of orthogonal volatile reporters that are detectable in exhaled breath. Here, we engineer multiplexed breath biomarkers that couple aberrant protease activities to exogenous volatile reporters. We designed novel intramolecular reactions that leverage protease-mediated aminolysis, enabling the sensing of a broad spectrum of proteases, and that each release a unique reporter in breath. This approach was validated in a mouse model of influenza to establish baseline sensitivity and specificity in a controlled inflammatory setting, and subsequently applied to diagnose lung cancer using an autochthonous Alk -mutant model. We show that combining multiplexed reporter signals with machine learning algorithms enables tumor progression tracking, treatment response monitoring, and detection of relapse after 30 minutes. Our multiplexed breath biopsy platform highlights a promising avenue for rapid, point-of-care diagnostics across diverse disease states.

Objectives: To determine the incidence of subglottic stenosis (SGS) in children after tracheostomy and identify risk factors for development., Study Design: Retrospective cohort., Methods: All patients (<18 years) undergoing tracheostomy at a tertiary children's hospital between 2015 and 2020 were included. Patients with a direct laryngoscopy (DL) concurrent with tracheostomy and a subsequent DL were included. Medical records, including operative reports, were reviewed to identify subglottic stenosis and associated risk factors., Results: A total of 140 patients were included with mean age at tracheostomy of 2.4 years (standard deviation [SD]: 4.3) (median: 0.5 years, interquartile range [IQR]: 0.3-1.5 years) and gestational age of 33.8 weeks (SD: 5.9) (median: 36 weeks, IQR: 28-39 weeks). At initial DL, 24% (N = 34) had subglottic injury and 26% (N = 37) developed SGS. The incidence of SGS after tracheostomy was 11.5 cases per 100 patients per year. At tracheostomy, lower birth weight (1.8 vs. 2.3 kg, p = 0.005), shorter gestational age (31.8 vs. 34.6 weeks, p = 0.01), younger age (0.8 vs. 2.9 years, p = 0.01), lower weight (5.8 vs. 14.7 kg, p = 0.01), and subglottic injury (44% vs. 21%, p = 0.01) were associated with the development of SGS. Multivariable logistic regression analysis associated birth weight (odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.31-0.75, p = 0.001) and early subglottic injury (OR: 3.22, 95% CI: 1.31-7.88, p = 0.01) with SGS development., Conclusions: The incidence of SGS after pediatric tracheostomy is estimated at 11.5 cases per 100 patients per year. Low birth weight and subglottic injury at the time of tracheostomy were associated with SGS in this vulnerable population of children., Level of Evidence: 3 Laryngoscope, 135:402-408, 2025., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Steroid hormones, including estrone (E1), androstadienedione (ADD), and androstenedione (AED), are prevalent in aquatic ecosystems and pose ecological risks due to their disruptive influence on fish populations. However, little consideration has been given to the endocrine disrupting effects of fish exposed to complex mixtures of hormones in the real world. In this study, adult female western mosquitofish (Gambusia affinis) were exposed to two concentrations of E1 (100 ng/L for E1L and 5,000 ng/L for E1H), ADD (100 ng/L for ADDL and 10,000 ng/L for ADDH), and AED (100 ng/L for AEDL and 10,000 ng/L for AEDH) as well as four binary mixture treatments (ADDL+E1L, ADDH+E1H, AEDL+E1L, and AEDH+E1H). After 42 d, their basic physiological parameters, secondary sex characteristics, gonadal health, embryo numbers, and HPG axis-related gene expression were evaluated. Results showed that the P/D ratio of hemal spines in AEDH+E1H exhibited a pronounced reduction, approximately half that of E1H. Moreover, the number of embryos in ADDH+E1H and AEDH+E1H was reduced by approximately 3-fold compared to E1H. Correspondingly, G. affinis exposure to ADDH+E1H and AEDH+E1H increased the proportion of degenerated oocytes. Exposure to combined treatments led to significant changes in the transcription of HPG axis-related genes in fish and displayed a certain degree of interaction. Furthermore, cluster heatmap analysis of target genes demonstrated that ADD+E1 and AED+E1 (both high and low concentrations) were far apart from ADD, AED and E1. Collectively, these observations imply the presence of antagonistic interactions in combined treatments, and the negative impact on the growth, maturation, and endocrine system of G. affinis varies accordingly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Progressive collapsing foot deformity (PCFD) and hallux valgus (HV) are complex 3-dimensional deformities of the foot. This study aimed to investigate structural and alignment differences between PCFD with and without HV using weightbearing computed tomography., Methods: Patients with PCFD aged 18 years or older who underwent weightbearing computed tomography were consecutively enrolled. Standard 2-dimensional PCFD and HV parameters were assessed semiautomatically. Foot and ankle offset, forefoot arch angle, and pronation of the medial column bones in the coronal plane, with the ground as a reference, were manually measured. Additionally, the angles from the inferior aspect of subtalar posterior facet of the talus to the ground (subtalar horizontal angle), from the inferior (posterior facet) to superior facets of the talus (infratalar-supratalar angle), and from the inferior (posterior facet) of the talus to the superior facet of the calcaneus (infratalar-supracalcaneal angle) were examined. HV deformity was defined by an HV angle of ≥15 degrees., Results: Among 72 feet (58 patients) studied, 33 displayed HV, whereas 39 did not. In the coronal plane, the PCFD with HV group showed a higher infratalar-supratalar angle and greater pronation at the first tarsometatarsal joint, first metatarsal bone, and head. The PCFD with HV group also exhibited greater naviculocuneiform joint supination. Generalized estimating equation logistic regression analysis revealed significant associations of HV deformity with the intrinsic rotation of the first metatarsal bone ( P  < .001), infratalar-supratalar angle ( P  = .004), and rotation of the first tarsometatarsal joint ( P  < .001)., Conclusion: This study confirmed significant structural and alignment differences between PCFD with and without HV. Notably, the infratalar-supratalar angle, rotation of the first tarsometatarsal joint, and intrinsic rotation of the first metatarsal bone were associated with HV deformity., Level of Evidence: Level III, retrospective comparative study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Cesar de Cesar Netto, MD, PhD, reports financial interests in CurveBeam, Paragon 28, and Disior, companies whose software has been specifically used for measuring radiographic parameters in this research. These interests include equity, royalties, advisory roles, and paid consultancy, and are compliant with applicable regulations and Duke University’s policies. Disclosure forms for all authors are available online.

Infectious diseases pose significant challenges to public health, leading to illness and even death. Vaccinations are vital for protecting society, yet beliefs in conspiracy theories related to infectious diseases increase vaccine hesitancy. This paper delves into vaccination decisions in the context of COVID-19, which continues to strain the health care system. While past research focuses on countering conspiratorial beliefs with cognitive persuasion interventions, we propose a social intervention as an alternative. Our novel intervention seeks to mitigate the effects of conspiratorial beliefs by fostering individuals' interdependent self-construal - viewing oneself in the context of social relationships. Interdependent self-construal was operationalized in multiple ways (measured in Studies 1, 2 and 3; manipulated to test causality in Studies 4 and 5). Conspiratorial beliefs were also manipulated in Study 5. The results show that the association between conspiratorial beliefs and vaccine hesitancy is weakened among individuals whose interdependent self-construal is more accessible. Moreover, this effect was mediated by prosocial motivation. We discuss the implications of our findings for developing and communicating health policies and propose potential contexts where this intervention may be relevant, thereby providing valuable insights into enhancing societal well-being in the face of conspiratorial beliefs., (© 2024 The Author(s). British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)