Deciphering the adaptation mechanism of anammox consortia under sulfamethoxazole stress: A model coupling resistance accumulation and interspecies-cooperation.

Sulfamethoxazole (SMX) is frequently detected in wastewater where anammox applications are promising. While it has been demonstrated that anammox consortia can adapt to SMX stress, the underlying community adaptation strategy has not yet been fully addressed. Therefore, in this study, we initially ascertained anammox consortia's ability to co-metabolize SMX in batch tests. Then, a 200-day domestication process of anammox consortia under SMX stress was carried out with community variations and transcriptional activities monitored by metagenomic and metatranscriptomic sequencing techniques. Despite the initial drop to 41.88 %, the nitrogen removal efficiency of the anammox consortia rebounded to 84.64 % post-domestication under 5 mg/L SMX. Meanwhile, a 4.85-fold accumulation of antibiotic resistance genes (ARGs) under SMX stress was observed as compared to the control group. Interestingly, the anammox consortia may unlock the SMX-inhibited folate synthesis pathway through a novel interspecies cooperation triangle among Nitrospira (NAA), Desulfobacillus denitrificans (DSS1), and the core anammox population Candidatus Brocadia sinica (AMX1), in which the modified dihydropteroate synthase (encoded by sul1) of NAA reconnected the symbiotic cooperation between AMX1 and DSS1. Overall, this study provides a new model for the adaptation strategies of anammox consortia to SMX stress.

Joint association of sedentary time and physical activity with abnormal heart rate recovery in young and middle-aged adults.

BACKGROUND: Abnormal heart rate recovery (HRR), representing cardiac autonomic dysfunction, is an important predictor of cardiovascular disease. Prolonged sedentary time (ST) is associated with a slower HRR. However, it is not clear how much moderate-to-vigorous physical activity (MVPA) is required to mitigate the adverse effects of sedentary behavior on HRR in young and middle-aged adults. This study aimed to examine the joint association of ST and MVPA with abnormal HRR in this population. METHODS: A cross-sectional analysis was conducted on 1253 participants (aged 20-50 years, 67.8% male) from an observational study assessing cardiopulmonary fitness in Fujian Province, China. HRR measured via cardiopulmonary exercise tests on a treadmill was calculated as the difference between heart rate at peak exercise and 2 min after exercise. When the HRR was ≤ 42 beats·minute-1 within this time, it was considered abnormal. ST and MVPA were assessed by the IPAQ-LF. Individuals were classified as having a low sedentary time (LST [< 6 h·day-1]) or high sedentary time (HST [≥ 6 h·day-1]) and according to their MVPA level (low MVPA [0-149 min·week-1], medium MVPA [150-299 min·week-1], high MVPA [≥ 300 min·week-1]). Finally, six ST-MVPA groups were derived. Associations between ST-MVPA groups with abnormal HRR incidence were examined using logistic regression models. RESULTS: 53.1% of the young and middle-aged adults had less than 300 min of MVPA per week. In model 2, adjusted for possible confounders (e.g. age, sex, current smoking status, current alcohol consumption, sleep status, body mass index), HST was associated with higher odds of an abnormal HRR compared to LST (odds ratio (OR) = 1.473, 95% confidence interval (CI) = 1.172-1.852). Compared with the reference group (HST and low MVPA), the HST and high MVPA groups have a lower chance of abnormal HRR (OR, 95% CI = 0.553, 0.385-0.795). Compared with individuals with HST and low MVPA, regardless of whether MVPA is low, medium, or high, the odds of abnormal HRR in individuals with LST is significantly reduced (OR, 95% CI = 0.515, 0.308-0.857 for LST and low MVPA; OR, 95% CI = 0.558, 0.345-0.902 for LST and medium MVPA; OR, 95% CI = 0.476, 0.326-0.668 for LST and high MVPA). CONCLUSION: Higher amounts of MVPA appears to mitigate the increased odds of an abnormal HRR associated with HST for healthy young and middle-aged adults.

Bio-based microplastic polylactic acid exerts the similar toxic effects to traditional petroleum-based microplastic polystyrene in mussels.

Microplastics (MPs) have accumulated in the oceans, causing adverse effects on marine organisms and the environment. Biodegradable polylactic acid (PLA) is considered as an excellent substitute for traditional petroleum-based plastics, but it is difficult to degrade completely and easily become MPs in the marine environment. To test the ecological risk of bio-based PLA, we exposed thick-shelled mussels (Mytilus coruscus) to bio-based PLA and petroleum-based polystyrene (PS) (at 102, 104, and 106 particles/L) for 14 days. The significant increase in enzyme activities related to oxidative stress and immune response showed that mussels were under physiological stress after MP ingestion. While enzyme activities of nerve conduction and energy metabolism were significantly disturbed after exposure. Meanwhile, normal physiological activities in respiration, ingestion and assimilation were also suppressed in association with enzyme changes. The negative effects of PS and PLA in mussels were not differentiated, and further integration analysis of integrated biomarker response (IBR) and principal component analysis (PCA) also showed that PLA would induce adverse effects in mussels and ecological risks as PS, especially at environmental concentrations. Therefore, it is necessary to pay more attention to the environmental and ecological risk of bio-based MP PLA accumulating in the marine environment.

SGLT2 Inhibitor Canagliflozin Reduces Visceral Adipose Tissue in db/db Mice by Modulating AMPK/KLF4 Signaling and Regulating Mitochondrial Dynamics to Induce Browning.

Obesity is characterized by excessive accumulation of adipose tissue (mainly visceral). The morphology and function of mitochondria are crucial for regulating adipose browning and weight loss. Research suggests that the SGLT2 inhibitor canagliflozin may induce weight loss through an unknown mechanism, particularly targeting visceral adipose tissue. While Krueppel-Like Factor 4 (KLF4) is known to be essential for energy metabolism and mitochondrial function, its specific impact on visceral adipose tissue remains unclear. We administered canagliflozin to db/db mice for 8 weeks, or exposed adipocytes to canagliflozin for 24 hours. The expression levels of browning markers, mitochondrial dynamics, and KLF4 were assessed. Then we validated the function of KLF4 through overexpression in vivo and in vitro. Adenosine monophosphate-activated protein kinase (AMPK) agonists, inhibitors, and KLF4 si-RNA were employed to elucidate the relationship between AMPK and KLF4. The findings demonstrated that canagliflozin significantly decreased body weight in db/db mice and augmented cold-induced thermogenesis. Additionally, canagliflozin increased the expression of mitochondrial fusion-related factors while reducing the levels of fission markers in epididymal white adipose tissue. These consistent findings were mirrored in canagliflozin-treated adipocytes. Similarly, overexpression of KLF4 in both adipocytes and db/db mice yielded comparable results. In all, canagliflozin mitigates obesity in db/db mice by promoting the brown visceral adipocyte phenotype through enhanced mitochondrial fusion via AMPK/KLF4 signaling.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities: The FOCUS Randomized Clinical Trial.

Importance: Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. Objective: To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Intervention: Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. Main Outcomes and Measures: The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. Results: A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. Conclusions and Relevance: The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Trial Registration: Chinese Clinical Trial Register: ChiCTR1900023241.

Effect of Lentinus sajor-caju on the chemical composition and antioxidant activity of highland barley straw under solid-state fermentation.

Introduction: The efficient utilization of straw resources as animal feed has gained considerable attention. The objective of this study was to evaluate whether Lentinus sajor-caju treatment alters the chemical composition and antioxidant activity of highland barley straw and enhances its functional value as a ruminant feed. Methods: The chemical composition, antioxidant capacity, and metabolomic profile of highland barley straw were determined after 21 days of solid-state fermentation with L. sajor-caju at 25°C. The differential metabolites between fermented and unfermented highland barley straw were identified by LC-MS and the relationship between the identified metabolites and antioxidant capacity was elucidated. Results: The results showed that, compared with untreated highland barley straw, the crude protein and ether extract contents were higher (51.55 and 76.43%, respectively) in highland barley straw after 21 days of incubation with L. sajor-caju, whereas the hemicellulose, cellulose, and acid detergent lignin contents were lower (2.48, 25.08, and 45%, respectively). The total antioxidant capacity was significantly higher in L. sajor-caju-treated than in untreated highland barley straw. In total, 600 differential metabolites (301 upregulated and 299 downregulated) were identified between L. sajor-caju-fermented and unfermented highland barley straw. Correlation analysis results showed that Fe2+ scavenging and total phenolic content were strongly correlated with total antioxidant capacity. Meanwhile, the differential flavonoid metabolites between fermented and unfermented highland barley straw were primarily associated with antioxidant activity, with kaempferol 3-xylosylglucoside, isoginkgetin, and rhoifolin being the most representative. Conclusion: Thus, this study demonstrates that L. sajor-caju could enhance the functional value of highland barley straw, showing the potential of L. sajor-caju for improving the utilization of agricultural straws in ruminants.

Experimental Warming Increased Cooked Rice Stickiness and Rice Thermal Stability in Three Major Chinese Rice Cropping Systems.

Climate warming is a critical environmental issue affecting rice production. However, its effects on cooked rice texture and rice thermal properties remain unstudied in China. To address this gap, we conducted a two-year multi-site field warming experiment using free-air temperature increase facilities across three major Chinese rice cropping systems. Interestingly, warming had a minimal impact on the hardness of cooked rice, while it significantly increased stickiness by an average of 16.3% under warming conditions. Moreover, compared to control treatments, rice flour exhibited a significant increase in gelatinization enthalpy, onset, peak, and conclusion temperatures under warming conditions, with average increments of 8.7%, 1.00 °C, 1.05 °C, and 1.17 °C, respectively. In addition, warming significantly declined the amylose content, remarkedly elevated the protein content and relative crystallinity, and altered the weight distribution of the debranched starch. Correlation analysis revealed significant relationships between cooked rice stickiness, rice flour thermal properties, amylose content, protein content, and partial starch structures. Therefore, warming-induced alterations in rice composition and starch structure collectively enhanced cooked rice stickiness and rice thermal stability.

Adaptive focus stacking for large depth-of-field microscopic structured-light 3D imaging.

This paper presents an adaptive focus stacking method for large depth-of-field (DOF) 3D microscopic structured-light imaging systems. Conventional focus stacking methods typically capture images under a series of pre-defined focus settings without considering the attributes of the measured object. Therefore, it is inefficient since some of the focus settings might be redundant. To address this problem, we first employ the focal sweep technique to reconstruct an initial rough 3D shape of the measured objects. Then, we leverage the initial 3D data to determine effective focus settings that focus the camera on the valid areas of the measured objects. Finally, we reconstruct a high-quality 3D point cloud using fringe images obtained from these effective focus settings by focus stacking. Experimental results demonstrate the success of the proposed method.

Effect of pre-plasma on terahertz radiation from two-color laser plasma filaments in a collinear geometry.

Terahertz (THz) radiation from air plasma in the presence of pre-plasma in a collinear geometry is investigated experimentally, where the pre-plasma is formed by a pre-pulse with a Gaussian beam profile and the measured THz radiation is driven by a main laser pulse. The pre-plasma has a de-focusing effect for the main pulse passing through it, which reduces the effective length of the plasma filament formed by the main laser pulse for THz radiation. It is found that only the part not overlapped by the pre-plasma can actually produce THz radiation. Thus, the amplitude of the THz pulse driven by the main pulse can be modified by changing the spatial separation between two plasma filaments. The experimental observations are qualitatively in agreement with our numerical simulation results. It is also found that the change of the time delay between the pre-pulse and the main pulse does not change the THz radiation amplitude for a given spatial separation. This study suggests a practical way for the manipulation of THz waves through an interaction between laser plasma filaments.

RASSF4 Attenuates Metabolic Dysfunction-Associated Steatotic Liver Disease Progression via Hippo Signaling and Suppresses Hepatocarcinogenesis.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a dynamic chronic liver disease closely related to metabolic abnormalities such as diabetes and obesity. MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). However, the mechanisms underlying the progression of MASLD and further progression to liver fibrosis and liver cancer are unknown. METHODS: In this study, we performed transcriptome analysis in livers from mice with MASLD and found suppression of a potential anti-oncogene, RAS association domain protein 4 (RASSF4). RASSF4 expression levels were measured in liver or tumor tissues of patients with MASH or HCC, respectively. We established RASSF4 overexpression and knockout mouse models. The effects of RASSF4 were evaluated by quantitative polymerase chain reaction, Western blotting, histopathological analysis, wound healing assays, Transwell assays, EdU incorporation assays, colony formation assays, sorafenib sensitivity assays, and tumorigenesis assays. RESULTS: RASSF4 was significantly down-regulated in MASH and HCC samples. Using liver-specific RASSF4 knockout mice, we demonstrated that loss of hepatic RASSF4 exacerbated hepatic steatosis and fibrosis. In contrast, RASSF4 overexpression prevented steatosis in MASLD mice. In addition, RASSF4 in hepatocytes suppressed the activation of hepatic stellate cells (HSCs) by reducing transforming growth factor beta secretion. Moreover, we found that RASSF4 is an independent prognostic factor for HCC. Mechanistically, we found that RASSF4 in the liver interacts with MST1 to inhibit YAP nuclear translocation through the Hippo pathway. CONCLUSIONS: These findings establish RASSF4 as a therapeutic target for MASLD and HCC.

JinLiDa granules alleviates cardiac hypertrophy and inflammation in diabetic cardiomyopathy by regulating TP53.

BACKGROUND: JinLiDa granules (JLD) is a traditional Chinese medicine (TCM) used to treat type 2 diabetes mellitus with Qi and Yin deficiency. Clinical evidence has shown that JLD can alleviate diabetic cardiomyopathy, but the exact mechanism is not yet clear. PURPOSE: The purpose of this study was to examine the potential role and mechanism of JLD in the treatment of diabetic cardiomyopathy through network pharmacological analysis and basic experiments. METHODS: The targets of JLD associated with diabetic cardiomyopathy were examined by network pharmacology. Protein interaction analysis was performed on the targets, and the associated pathways were searched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Diabetic mice were treated with low or high doses of JLD by gavage, and AC16 and H9C2 cardiomyocytes exposed to high-glucose conditions were treated with JLD. The analysis results were verified by various experimental techniques to examine molecular mechanisms. RESULTS: Network pharmacological analysis revealed that JLD acted on the tumor suppressor p53 (TP53) during inflammation and fibrosis associated with diabetic cardiomyopathy. The results of basic experiments showed that after JLD treatment, ventricular wall thickening in diabetic mouse hearts was attenuated, cardiac hypertrophy and myocardial inflammation were alleviated, and the expression of cardiac hypertrophy- and inflammation-related factors in cardiomyocytes exposed to a high-glucose environment was decreased. Cardiomyocyte morphology also improved after JLD treatment. TP53 expression and the tumor necrosis factor (TNF) and transforming growth factor beta-1 (TGFß1) signaling pathways were significantly altered, and inhibiting TP53 expression effectively alleviated the activation of the TNF and TGFß1 signaling pathways under high glucose conditions. Overexpression of TP53 activated these signaling pathways. CONCLUSIONS: JLD acted on TP53 to regulate the TNF and TGFß1 signaling pathways, effectively alleviating cardiomyocyte hypertrophy and inflammation in high glucose and diabetic conditions. Our study provides a solid foundation for the future treatment of diabetic cardiomyopathy with JLD.

Aberrant expression of NEDD4L disrupts mitochondrial homeostasis by downregulating CaMKKß in diabetic kidney disease.

Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKß/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKß in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKß. Moreover, deletion of NEDD4L under high glucose conditions prevented rapid CaMKKß protein degradation. In vitro studies revealed that the aberrant expression of NEDD4L negatively influences the protein stability of CaMKKß. This study also explored the role of NEDD4L in DKD by using AAV-shNedd4L in db/db mice. These findings confirmed that NEDD4L inhibition leads to a decrease in urine protein excretion, tubulointerstitial fibrosis, and oxidative stress, and mitochondrial dysfunction. Further in vitro studies demonstrated that si-Nedd4L suppressed mitochondrial fission and reactive oxygen species (ROS) production, effects antagonized by si-CaMKKß. In summary, the findings provided herein provide strong evidence that dysregulated NEDD4L disturbs mitochondrial homeostasis by negatively modulating CaMKKß in the context of DKD. This evidence underscores the potential of therapeutic interventions targeting NEDD4L and CaMKKß to safeguard renal tubular function in the management of DKD.

Points of interest linear attention network for real-time non-rigid liver volume to surface registration.

BACKGROUND: In laparoscopic liver surgery, accurately predicting the displacement of key intrahepatic anatomical structures is crucial for informing the doctor's intraoperative decision-making. However, due to the constrained surgical perspective, only a partial surface of the liver is typically visible. Consequently, the utilization of non-rigid volume to surface registration methods becomes essential. But traditional registration methods lack the necessary accuracy and cannot meet real-time requirements. PURPOSE: To achieve high-precision liver registration with only partial surface information and estimate the displacement of internal liver tissues in real-time. METHODS: We propose a novel neural network architecture tailored for real-time non-rigid liver volume to surface registration. The network utilizes a voxel-based method, integrating sparse convolution with the newly proposed points of interest (POI) linear attention module. POI linear attention module specifically calculates attention on the previously extracted POI. Additionally, we identified the most suitable normalization method RMSINorm. RESULTS: We evaluated our proposed network and other networks on a dataset generated from real liver models and two real datasets. Our method achieves an average error of 4.23 mm and a mean frame rate of 65.4 fps in the generation dataset. It also achieves an average error of 8.29 mm in the human breathing motion dataset. CONCLUSIONS: Our network outperforms CNN-based networks and other attention networks in terms of accuracy and inference speed.

The effect of acupuncture on gastrointestinal recovery after abdominal surgery: a narrative review from clinical trials.

Abdominal surgery is a critical surgery, with more and more attention being paid to postoperative life quality and associated complications in recent years. Among these complications, postoperative gastrointestinal dysfunction is the most common complication of abdominal surgery. Acupuncture therapy is a treatment approach based on the Traditional Chinese Medicine (TCM) theory, and its feasibility in aiding the gastrointestinal recovery after abdominal surgery is supported by both TCM theory and animal experiments. A lot of clinical research has been conducted to evaluate its efficacy, albeit with limitations and at preliminary stages. Moreover, intervention timing, acupoint selection, and patient benefits should also be considered in clinical practices. This article summarizes the progress of clinical research on acupuncture therapy in the gastrointestinal recovery after abdominal surgery, and discusses related issues and operations, with the aim to provide new insights and prospect for the incorporation of acupuncture into the Enhanced Recovery After Surgery (ERAS) protocol.

Clinical features of patients with mutations in genes for nanophthalmos.

BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (PRSS56), membrane-type frizzled-related protein (MFRP), myelin regulatory factor (MYRF) and transmembrane protein 98 (TMEM98) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. METHODS: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. RESULTS: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP. Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. CONCLUSION: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.

Millijoule Terahertz Radiation from Laser Wakefields in Nonuniform Plasmas.

We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.

Mechanical-Enhanced and Durable Zwitterionic Hydrogel Coating for Inhibiting Coagulation and Reducing Bacterial Infection.

Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-CuII (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.

Interpretation of Frequency Effect for High-Strength Steels with Three Different Strength Levels via Crystal Plasticity Finite Element Method.

The fatigue behavior of a high-strength bearing steel tempered under three different temperatures was investigated with ultrasonic frequency and conventional frequency loading. Three kinds of specimens with various yield strengths exhibited obvious higher fatigue strengths under ultrasonic frequency loading. Then, a 2D crystal plasticity finite element method was adopted to simulate the local stress distribution under different applied loads and loading frequencies. Simulations showed that the maximum residual local stress was much smaller under ultrasonic frequency loading in contrast to that under conventional frequency at the same applied load. It was also revealed that the maximum local stress increases with the applied load under both loading frequencies. The accumulated plastic strain was adopted as a fatigue indicator parameter to characterize the frequency effect, which was several orders smaller than that obtained under conventional loading frequencies when the applied load was fixed. The increment of accumulated plastic strain and the load stress amplitude exhibited a linear relationship in the double logarithmic coordinate system, and an improved fatigue life prediction model was established.

Determinants of Parental Intention to Vaccinate Young Adolescent Girls against the Human Papillomavirus in Taiwan: An Online Survey Study.

Since 2018, Taiwan has included the human papillomavirus (HPV) vaccination into its national immunization program for junior high school girls. However, the reports of side effects following vaccination have increased parental concerns. This study investigated parental intentions regarding the HPV vaccination for their daughters and related factors in Taiwan. A total of 213 parents of girls aged between 12 and 15 years participated in an online survey. The survey collected data on various factors, including the parental intention to vaccinate their daughters against HPV; the motivation behind the vaccinations, as measured using the Motors of Human Papillomavirus Vaccination Acceptance Scale; an understanding of the reasons behind the government's promotion of HPV vaccinations; concerns regarding the side effects of vaccinations for their daughters; an awareness of the reported side effects of HPV vaccines experienced by some individuals; the exposure to information on HPV vaccines from social media; and mental health status, measured using the Brief Symptom Rating Scale. The associations between these variables and the parental intention to vaccinate their daughters against HPV were examined using a multivariable linear regression analysis model. The findings revealed a moderate to high level of intention among participants to vaccinate their daughters against HPV. Parents who perceived a greater value in HPV vaccination for their daughters' health (B = 0.524, standard error [se] = 0.039, p < 0.001) and had greater autonomy in decision-making regarding vaccination (B = 0.086, se = 0.038, p = 0.026) exhibited a higher intention to vaccinate their daughters against HPV. Conversely, parents who expressed greater concern regarding the side effects of HPV vaccines for their daughters had a lower intention to vaccinate (B = -0.762, se = 0.203, p < 0.001). Based on these findings, this study recommends integrating these factors into the design of intervention programs aimed at enhancing parental intentions to vaccinate their daughters against HPV.

A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVE: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). METHODS: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. RESULTS: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). CONCLUSION: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.