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Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg. Results indicated that added 50 and 500 mg/kg nano-ZnOs showed minimal toxicity. However, 5000 mg/kg nano-ZnOs significantly decreased body weight (from week 4 to 16) and increased the relative weights of the pancreas, brain and lung. Added 5000 mg/kg nano-ZnOs significantly increased the serum glutamic-pyruvic transaminase activity and zinc content, and significantly enhanced mRNA expression of zinc metabolism-related genes, including metallothionein 1(32.66 folds), metallothionein 2 (31.42 folds), ZIP8 (2.21folds), ZIP14 (2.45 folds), ZnT1 (4.76 folds), ZnT2 (6.19 folds) and ZnT4 (1.82 folds). The biodistribution determination showed that there was a significant accumulation of zinc in the liver, pancreas, kidney, and bones (tibia and fibula) after receiving 5000 mg/kg nano-ZnO diet, while no significant effects on Cu, Fe, and Mn levels, except for liver Fe content and pancreas Mn level. Our results demonstrated that long term exposure to 50 and 500 mg/kg nano-ZnO diets showed minimal toxicity. However, high dose of nano-ZnOs (5000 mg/kg) caused toxicity on development, and altered the zinc metabolism and biodistribution in mice.

While large scientific and medical evidence has demonstrated the increased risk of death and cardiovascular mortality in patients with severe AS, the independent contribution of moderate AS to an increased risk of death remains uncertain. We conducted a multicenter study including a cohort of 30,865 US patients and another cohort of 217,599 Australian patients with equivalent echocardiographic and aortic valve profiling over the same period (2003-2017). During a median 5.2 years (US) and 4.4 years (Australian) follow-up, the risk of death (hazard ratio) of patients with moderate AS as compared to those without AS was 1.66 (95%CI 1.52-1.80) and 1.37 (95%CI 1.34-1.41) in the US and Australian cohorts, even after adjusting this analysis for age and sex. This increased risk of death and cardiovascular mortality (odds ratio) in patients with moderate AS was consistent also across subgroups of left ventricular ejection fraction (LVEF) (subgroups of LVEF < 40%, 40-49%, 50-59%, and ≥ 60%: OR of moderate AS for CV mortality 2.0 [95%CI 1.4-2.7], 1.7 [95%CI 1.2-2.4], 1.5 [95%CI 1.1-1.9], and 1.4 [95%CI 1.2-1.6], respectively). The findings of this study suggest that patients with moderate AS have a potential increased risk of death and cardiovascular mortality, regardless of age, sex, and LVEF. Hence, these data suggest the need to develop specific strategies to detect and treat individuals with moderate AS.

Food contamination caused by food-spoilage bacteria and pathogenic bacteria seriously affects public health. Staphylococcus aureus is a typical foodborne pathogen which easily forms biofilm. Once biofilm is formed, it is difficult to remove. The use of nanotechnology for antibiofilm purposes is becoming more widespread because of its ability to increase the bioavailability and biosorption of many drugs. In this work, chitosan nanoparticles (CSNPs) were prepared by the ion–gel method with polyanionic sodium triphosphate (TPP). Cinnamaldehyde (CA) was loaded onto the CSNPs. The particle size, potential, morphology, encapsulation efficiency and in vitro release behavior of cinnamaldehyde–chitosan nanoparticles (CSNP-CAs) were studied, and the activity of CA against S. aureus biofilms was evaluated. The biofilm structure on the silicone surface was investigated by scanning electron microscopy (SEM). Confocal laser scanning microscopy (CLSM) was used to detect live/dead organisms within biofilms. The results showed that CSNP-CAs were dispersed in a circle with an average diameter of 298.1 nm and a zeta potential of +38.73 mV. The encapsulation efficiency of cinnamaldehyde (CA) reached 39.7%. In vitro release studies have shown that CA can be continuously released from the CSNPs. Compared with free drugs, CSNP-CAs have a higher efficacy in removing S. aureus biofilm, and the eradication rate of biofilm can reach 61%. The antibiofilm effects of CSNP-CAs are determined by their antibacterial properties. The minimum inhibitory concentration (MIC) of CA is 1.25 mg/mL; at this concentration the bacterial cell wall ruptures and the permeability of the cell membrane increases, which leads to leakage of the contents. At the same time, we verified that the MIC of CSNP-CAs is 2.5 mg/mL (drug concentration). The synergy between CA and CSNPs demonstrates the combinatorial application of a composite as an efficient novel therapeutic agent against antibiofilm. We can apply it in food preservation and other contexts, providing new ideas for food preservation.

Background: Polygonatum sibiricum (PS), a perennial herbaceous plant belonging to the Liliaceae family, is widely distributed in China and other East Asian countries. PS has been used as food and medicine for thousands of years, and its rhizomes are rich in Polygonatum sibiricum polysaccharides (PSP), which exhibit various bioactivities, yet their structural features and therapeutic mechanisms against ulcerative colitis (UC) remain unclear. Methods: A homogeneous polysaccharide, PSP-1b (57.45 kDa), was isolated from the rhizomes of PS via ion-exchange and gel filtration chromatography and structurally characterized using chromatographic and spectroscopic methods. In vivo, its effects were evaluated in a dextran sulfate sodium (DSS)-induced mouse model of UC, while in vitro mechanisms were explored using macrophages stimulated with lipopolysaccharide (LPS) and neutrophil extracellular traps (NETs). Results: PSP-1b was identified as a neutral polysaccharide with minimal branching. Its primary structural backbone was largely composed of →4)-β-D-Galp-(1→ residues. A portion of these backbone residues was substituted at the O-6 position by side chains primarily composed of β-D-Galp-(1→ units. In vivo, PSP-1b significantly alleviated DSS-induced colitis by reducing inflammatory cytokine secretion, suppressing colonic macrophage infiltration, and reversing neutrophil extracellular traps (NETs) deposition. In vitro, PSP-1b directly interacted with TLR4, inhibited the MAPK/NF-κB signaling pathway, and attenuated LPS- and NET-induced macrophage polarization and inflammation. Conclusions: PSP-1b as a promising candidate for functional foods or therapeutic agents targeting inflammatory bowel disease.

Background Speech disorders and freezing of gait (FOG) in Parkinson's disease (PD) may have some common pathological mechanisms. The purpose of this study was to compare the acoustic parameters of PD patients with dopamine-responsive FOG (PD-FOG) and without FOG (PD-nFOG) during \"ON state\" and explore the ability of \"ON state\" voice features in distinguishing PD-FOG from PD-nFOG. Methods A total of 120 subjects, including 40 PD patients with dopamine-responsive FOG, 40 PD-nFOG, and 40 healthy controls (HCs) were recruited. All subjects underwent neuropsychological tests. Speech samples were recorded through the sustained vowel pronunciation tasks during the \"ON state\" and then analyzed by the Praat software. A set of 27 voice features was extracted from each sample for comparison. Support vector machine (SVM) was used to build mathematical models to classify PD-FOG and PD-nFOG. Results Compared with PD-nFOG, the jitter, the standard deviation of fundamental frequency (F0SD), the standard deviation of pulse period (pulse period SD) and the noise-homophonic-ratio (NHR) were increased, and the maximum phonation time (MPT) was decreased in PD-FOG. The above voice features were correlated with the freezing of gait questionnaire (FOGQ). The average accuracy, specificity, and sensitivity of SVM models based on 27 voice features for classifying PD-FOG and PD-nFOG were 73.57%, 75.71%, and 71.43%, respectively. Conclusions PD-FOG have more severe voice impairment than PD-nFOG during \"ON state\".

Previous studies have reported that white matter hyperintensities (WMHs) are associated with freezing of gait (FOG), but it is not clear whether their distribution areas have correlations with FOG in Parkinson's disease (PD) and the potential influencing factors about WMHs. Two hundred and forty-six patients with PD who underwent brain MRI were included. Participants were divided into PD with FOG (  = 111) and PD without FOG (  = 135) groups. Scheltens score was used to assess the WMHs burden in the areas of deep white matter hyperintensities (DWMHs), periventricular hyperintensities (PVHs), basal ganglia hyperintensities (BGHs), and infratentorial foci of hyperintensities (ITF). Whole brain WMHs volume was evaluated by automatic segmentation. Binary logistic regression was used to evaluate relationships between WMHs and FOG. The common cerebrovascular risk factors that may affect WMHs were evaluated by mediation analysis. There were no statistical differences between PD with and without FOG groups in whole brain WMHs volume, total Scheltens score, BGHs, and ITF. Binary logistic regression showed that the total scores of DWMHs (OR = 1.094; 95% CI, 1.001, 1.195;  = 0.047), sum scores of PVHs and DWMHs (OR = 1.080; 95% CI, 1.003, 1.164;  = 0.042), especially the DWMHs in frontal (OR = 1.263; 95% CI, 1.060, 1.505  = 0.009), and PVHs in frontal caps (OR = 2.699; 95% CI, 1.337, 5.450;  = 0.006) were associated with FOG. Age, hypertension, and serum alkaline phosphatase (ALP) are positively correlated with scores of DWMHs in frontal and PVHs in frontal caps. These results indicate that WMHs distribution areas especially in the frontal of DWMHs and PVHs play a role in PD patients with FOG.

AbstractObjectivesTo characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza.DesignRetrospective cohort study.SettingUnited States.Participants883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics.Main outcome measuresAll cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days.ResultsThe covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference −0.12) and had a lower proportion of women (51.7% v 57.3%, −0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, −0.12), heart failure (43.4% v 49.9%, −0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, −0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;–0.1%, −0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%.ConclusionsMedicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.