The application of multi-criteria decision analysis in evaluating the value of drug-oriented intervention: a literature review.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

A colorimetric tandem combination of CRISPR/Cas12a with dual functional hybridization chain reaction for ultra-sensitive detection of Mycobacterium bovis.

Tuberculosis caused by Mycobacterium bovis poses a global infectious threat to humans and animals. Therefore, there is an urgent need to develop a sensitive, precise, and easy-to-readout strategy. Here, a novel tandem combination of a CRISPR/Cas12a system with dual HCR (denoted as CRISPR/Cas12a-D-HCR) was constructed for detecting Mycobacterium bovis. Based on the efficient trans-cleavage activity of the active CRISPR/Cas12a system, tandem-dsDNA with PAM sites was established using two flexible hairpins, providing multiple binding sites with CRISPR/Cas12a for further amplification. Furthermore, the activation of Cas12a initiated the second hybridization chain reaction (HCR), which integrated complete G-quadruplex sequences to assemble the hemin/G-quadruplex DNAzyme. With the addition of H2O2 and ABTS, a colorimetric signal readout strategy was achieved. Consequently, CRISPR/Cas12a-D-HCR achieved a satisfactory detection linear range from 20 aM to 50 fM, and the limit of detection was as low as 2.75 aM with single mismatched recognition capability, demonstrating good discrimination of different bacterial species. Notably, the practical application performance was verified via the standard addition method, with the recovery ranging from 96.0% to 105.2% and the relative standard deviations (RSD) ranging from 0.95% to 6.45%. The proposed CRISPR/Cas12a-D-HCR sensing system served as a promising application for accurate detection in food safety and agricultural fields.

Comparison of Down Sizing Strategy (HANGZHOU Solution) and Standard Annulus Sizing Strategy in type 0 bicuspid aortic stenosis patients undergoing transcatheter aortic valve replacement: Rationale and design of a randomized clinical trial.

BACKGROUND: There has not been a consensus on the prothesis sizing strategy in type 0 bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Modifications to standard annular sizing strategies might be required due to the distinct anatomical characteristics. We have devised a Down Sizing Strategy for TAVR using a self-expanding valve specifically for patients with type 0 bicuspid AS. The primary aim of this study is to compare the safety and efficacy of Down Sizing Strategy with the Standard Annulus Sizing Strategy in TAVR for patients with type 0 bicuspid AS. TRIAL DESIGN: It is a prospective, multi-center, superiority, single-blinded, randomized controlled trial comparing the Down Sizing and Standard Annulus Sizing Strategy in patients with type 0 bicuspid aortic stenosis undergoing transcatheter aortic valve replacement. Eligible participants will include patients with severe type 0 bicuspid AS, as defined by criteria such as mean gradient across aortic valve ≥40 mmHg, peak aortic jet velocity ≥4.0 m/s, aortic valve area (AVA) ≤1.0 cm², or AVA index ≤0.6 cm2/m2. These patients will be randomly assigned, in a 1:1 ratio, to either the Down Sizing Strategy group or the Standard Sizing Strategy group. In the Down Sizing Strategy group, a valve one size smaller will be implanted if the "waist sign" manifests along with less than mild regurgitation during balloon pre-dilatation. The primary end point of the study is a composite of VARC-3 defined device success, absence of both permanent pacemaker implantation due to high-degree atrioventricular block and new-onset complete left bundle branch block. CONCLUSION: This study will compare the safety and efficacy of Down Sizing Strategy with the Standard Annulus Sizing Strategy and provide valuable insights into the optimal approach for sizing in TAVR patients with type 0 bicuspid AS. We hypothesize that the Down Sizing Strategy will demonstrate superiority when compared to the Standard Annulus Sizing Strategy. (Down Sizing Strategy (HANGZHOU Solution) vs Standard Sizing Strategy TAVR in Bicuspid Aortic Stenosis (Type 0) (TAILOR-TAVR), NCT05511792).

Morphological Integrated Preparation Method and Implementation of Inorganic/Organic Dual-Phase Composite Gradient Bionic Bone Scaffold.

Large bone defects caused by congenital deformities and acquired accidents are increasing day by day. A large number of patients mainly rely on artificial bone for repair. However, artificial bone cannot fully imitate the structure and composition of human bone, resulting in a large gap with autologous bone function. Therefore, this article proposes a continuous preparation method for inorganic/organic biphasic composite gradient biomimetic bulk bone scaffolds. First, a controllable gradient hybrid forming platform for inorganic/organic dual-phase biomaterials was constructed, and the feeding control strategy was studied to achieve precise control of the feeding of sodium alginate/gelatin composite organic materials and hydroxyapatite inorganic materials. The speed is, respectively, sent from the corresponding feeding nozzle to the mixing chamber to realize the uniform mixing of the biphasic material and the extrusion of the composite material, and the inorganic/organic biphasic composite gradient biomimetic bone scaffold with gradual structure and composition is prepared. Second, to prove the superiority of the preparation method, the physicochemical and biological properties of the prepared scaffolds were evaluated. The test results showed that the morphological characteristics of the biphasic composite gradient bone scaffold showed good microscopic porosity and the structure and composition showed gradients. The mechanical properties are close to that of human bone tissue and in vitro cell experiments show that the scaffold has good biocompatibility and bioactivity. In conclusion, this article provides a new type of bone scaffold preparation technology and equipment for the field of tissue engineering, which has research value and application prospects.

APAF1 Silencing Ameliorates Diabetic Retinopathy by Suppressing Inflammation, Oxidative Stress, and Caspase-3/GSDME-Dependent Pyroptosis.

Objective: Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR. Methods: Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells. Results: Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1ß, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells. Conclusion: APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis.

Population-based deep image prior for dynamic PET denoising: A data-driven approach to improve parametric quantification.

The high noise level of dynamic Positron Emission Tomography (PET) images degrades the quality of parametric images. In this study, we aim to improve the quality and quantitative accuracy of Ki images by utilizing deep learning techniques to reduce the noise in dynamic PET images. We propose a novel denoising technique, Population-based Deep Image Prior (PDIP), which integrates population-based prior information into the optimization process of Deep Image Prior (DIP). Specifically, the population-based prior image is generated from a supervised denoising model that is trained on a prompts-matched static PET dataset comprising 100 clinical studies. The 3D U-Net architecture is employed for both the supervised model and the following DIP optimization process. We evaluated the efficacy of PDIP for noise reduction in 25%-count and 100%-count dynamic PET images from 23 patients by comparing with two other baseline techniques: the Prompts-matched Supervised model (PS) and a conditional DIP (CDIP) model that employs the mean static PET image as the prior. Both the PS and CDIP models show effective noise reduction but result in smoothing and removal of small lesions. In addition, the utilization of a single static image as the prior in the CDIP model also introduces a similar tracer distribution to the denoised dynamic frames, leading to lower Ki in general as well as incorrect Ki in the descending aorta. By contrast, as the proposed PDIP model utilizes intrinsic image features from the dynamic dataset and a large clinical static dataset, it not only achieves comparable noise reduction as the supervised and CDIP models but also improves lesion Ki predictions.

[Clinical Study of Allogeneic Hematopoietic Stem Cell Transplantation Patients with Co-Reactivation of Cytomegalovirus and Epstein-Barr Virus].

OBJECTIVE: To explore the clinical characteristics and risk factors of cytomegalovirus(CMV) and Epstein-Barr virus(EBV) co-reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its influence on prognosis. METHODS: The clinical data of 222 patients who received allo-HSCT from January 2015 to December 2020 were collected, and the patients were divided into groups according to the occurrence of CMV and EBV infection. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard regression model was used to analyze the risk factors of co-reactivation of CMV and EBV. RESULTS: After allo-HSCT, there were 30 patients with co-reactivation of CMV and EBV (CMV++EBV+ group), 101 patients with CMV viremia (CMV+ group), 149 patients with EBV viremia (EBV+ group), and 28 patients with CMV and EBV inactivation (CMV-+ EBV- group). Compared with the other groups, the incidence of acute graft-versus-host disease (aGVHD) and hemorrhagic cystitis (HC) was higher in CMV++ EBV+ groups (53.3% vs 42.6%, 36.9%, 17.9%, P < 0.001; 36.7% vs 32.7%, 22.8%, 10.7%, P =0.042). The incidence of post-transplant lymphoproliferative disease (PTLD) in CMV++ EBV+ group was similar to CMV+ group and EBV+ group (3.3% vs 3.0%, 3.4%, P =0.811). Univariate and multivariate analysis showed that the persistent time of CMV and EBV after transplantation were independent risk factors for co-reactivation of CMV and EBV. Compared with the other groups, the 2-year overall survival (OS) rate and 2-year disease-free survival (DFS) rate of patients in CMV++EBV+ group were lower (46.7% vs 74.9%, 83.4%, 71.4%, P < 0.001; 46.7% vs 70.9%, 79.5%, 69.9%, P =0.002), and 2-year non-recurrence mortality (NRM) was higher (48.2% vs 22%, 13.6%, 18.7%, P <0.001). CONCLUSION: The persistent time of CMV and EBV after transplantation are independent risk factors for patients with co-reactivation of CMV and EBV. Patients with co-reactivation of CMV and EBV had lower OS and DFS rate and higher NRM, suggesting that the clinical prognosis of the patients are worse.

Health Qigong Mawangdui Guidance can improve pelvic floor muscle function and quality of life in females with stress urinary incontinence: A randomized controlled trial pilot study.

BACKGROUND: Urinary incontinence (UI) is a great problem of public health, especially for women's quality of life. UI afflicts at least 21.6% of the global population, and more than half of the UI is related to female stress urinary incontinence (SUI). Mawangdui Guidance plays an important role in preventing diseases and maintaining health. METHODS: Sixty female patients with SUI were randomly divided into a control group (n = 30) and an experimental group (n = 30). Patients in both groups were treated with basic rehabilitation therapy under the guidance of rehabilitation therapists who were trained in Mawangdui Guidance, based on the former, the experimental group was taught to exercise Mawangdui Guidance(including selected movements: "Qishi," "Longdeng," "Chishi," and "Yinyao"), while the control group performed Kegel exercise with a procedure of 20 min, six times per week for 6 weeks. The function was mainly evaluated by the 1 h pad-test, incontinence quality of life questionnaire (I-QOL), and international consultation on incontinence questionnaire urinary incontinence short form (ICI-Q-SF). In addition, evaluation of pelvic floor muscle function was also included in our assessment. RESULTS: The leakage of urine in the 1 h pad-test was significantly decreased in both two groups after treatment (P < .05), and the urine leakage in the experimental group was significantly less than that in the control group (P < .05). The muscle strength of type I and II muscle fibers of the pelvic floor, intravaginal pressure, and I-QOL score in both two groups were increased after treatment; moreover, the experimental group was more significant than the control group (P <.05). The fatigue degree of type I and type II muscle fibers of the pelvic floor, and the ICI-Q-SF score in both groups were significantly improved after treatment (P < .05); however, there were no differences between these two groups. The total effective rate of the experimental group was 90.00%, and 76.67% in the control group (P <.05). CONCLUSION: Mawangdui Guidance can effectively improve the function of pelvic floor muscle, improve the ability of urine storage and control, and alleviate the symptoms of female patients with SUI. However, the international research on Mawangdui Guidance is very limited, and more in-depth research is needed.

A high heterozygosity genome assembly of Aedes albopictus enables the discovery of the association of PGANT3 with blood-feeding behavior.

The Asian tiger mosquito, Aedes albopictus, is a global invasive species, notorious for its role in transmitting dangerous human arboviruses such as dengue and Chikungunya. Although hematophagous behavior is repulsive, it is an effective strategy for mosquitoes like Aedes albopictus to transmit viruses, posing a significant risk to human health. However, the fragmented nature of the Ae. albopictus genome assembly has been a significant challenge, hindering in-depth biological and genetic studies of this mosquito. In this research, we have harnessed a variety of technologies and implemented a novel strategy to create a significantly improved genome assembly for Ae. albopictus, designated as AealbF3. This assembly boasts a completeness rate of up to 98.1%, and the duplication rate has been minimized to 1.2%. Furthermore, the fragmented contigs or scaffolds of AealbF3 have been organized into three distinct chromosomes, an arrangement corroborated through syntenic plot analysis, which compared the genetic structure of Ae. albopictus with that of Ae. aegypti. Additionally, the study has revealed a phylogenetic relationship suggesting that the PGANT3 gene is implicated in the hematophagous behavior of Ae. albopictus. This involvement was preliminarily substantiated through RNA interference (RNAi) techniques and behavioral experiment. In summary, the AealbF3 genome assembly will facilitate new biological insights and intervention strategies for combating this formidable vector of disease. The innovative assembly process employed in this study could also serve as a valuable template for the assembly of genomes in other insects characterized by high levels of heterozygosity.

See farther and more: a master-slave UAVs based synthetic optical aperture imaging system with wide and dynamic baseline.

An open challenge remained in designing an optical system to capture the aerial image with a wide field of view (FoV) and high resolution. The optical system of one camera from a single unmanned aerial vehicle (UAV) can hardly promise the FoV and resolution. The conventional swarm UAVs can form the camera array with a short or fixed baseline. They can capture the images with a wide FoV and high resolution, but the cost is the requirement of many UAVs. We aim to design a camera array with a wide and dynamic baseline to reduce the demand for UAVs to organize a synthetic optical aperture. In this thought, we propose a master-slave UAVs-based synthetic optical aperture imaging system with a wide and dynamic baseline. The system consists of one master UAV and multiple slave UAVs. Master and slave UAVs provide the global and local FoVs, respectively, and improve the efficiency of image acquisition. In such a system, fusing UAV images becomes a new challenge due to two factors: (i) the small FoV overlap of slave UAVs and (ii) the gap in resolution scale from slave to master UAV images. To deal with it, a coarse-to-fine stitching method is proposed to stitch up the multi-view images into one to obtain a wide FoV with high resolution. A video stabilization method has also been designed for the proposed imaging system. Challenges caused by wide and dynamic baselines can thus be solved by the above methods. Actual data experiments demonstrate that the proposed imaging system achieves high-quality imaging results.

Identifying and validating potential therapeutic targets for septic heart failure and the cardioprotective effects of lycorine.

BACKGROUND: Septic heart failure has been recognized as a puzzle since antiquity and poses a major challenge to modern medicine. Our previous work has demonstrated the potential effects of lycorine (LYC) on sepsis and septic myocardial injury. Nonetheless, further exploration is needed to elucidate the underlying cellular and molecular mechanisms. METHODS: In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure. PURPOSE: This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice. RESULTS: Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury. CONCLUSION: In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.

DuDoCFNet: Dual-Domain Coarse-to-Fine Progressive Network for Simultaneous Denoising, Limited-View Reconstruction, and Attenuation Correction of Cardiac SPECT.

Single-Photon Emission Computed Tomography (SPECT) is widely applied for the diagnosis of coronary artery diseases. Low-dose (LD) SPECT aims to minimize radiation exposure but leads to increased image noise. Limited-view (LV) SPECT, such as the latest GE MyoSPECT ES system, enables accelerated scanning and reduces hardware expenses but degrades reconstruction accuracy. Additionally, Computed Tomography (CT) is commonly used to derive attenuation maps (µ-maps) for attenuation correction (AC) of cardiac SPECT, but it will introduce additional radiation exposure and SPECT-CT misalignments. Although various methods have been developed to solely focus on LD denoising, LV reconstruction, or CT-free AC in SPECT, the solution for simultaneously addressing these tasks remains challenging and under-explored. Furthermore, it is essential to explore the potential of fusing cross-domain and cross-modality information across these interrelated tasks to further enhance the accuracy of each task. Thus, we propose a Dual-Domain Coarse-to-Fine Progressive Network (DuDoCFNet), a multi-task learning method for simultaneous LD denoising, LV reconstruction, and CT-free µ-map generation of cardiac SPECT. Paired dual-domain networks in DuDoCFNet are cascaded using a multi-layer fusion mechanism for cross-domain and cross-modality feature fusion. Two-stage progressive learning strategies are applied in both projection and image domains to achieve coarse-to-fine estimations of SPECT projections and CT-derived µ-maps. Our experiments demonstrate DuDoCFNet's superior accuracy in estimating projections, generating µ-maps, and AC reconstructions compared to existing single- or multi-task learning methods, under various iterations and LD levels. The source code of this work is available at https://github.com/XiongchaoChen/DuDoCFNet-MultiTask.

Pleiotropic role of GAS6 in cardioprotection against ischemia-reperfusion injury.

INTRODUCTION: Myocardial ischemia-reperfusion (IR) injury is a common medical issue contributing to the onset and progression of ischemic heart diseases (IHD). Growth arrest-specific gene 6 (GAS6), a vitamin K-dependent secretory protein, promotes cell proliferation and inhibits inflammation and apoptosis through binding with Tyro3, Axl, and Mertk (TAM) receptors. OBJECTIVES: Our study aimed to examine the effect of GAS6 pathways activation as a potential new treatment in myocardial IR injury. METHODS: Gain- and loss-of-function experiments were utilized to determine the roles of GAS6 in the pathological processes of myocardial IR injury. RESULTS: Our results revealed down-regulated levels of GAS6, Axl, and SIRT1 in murine hearts subjected to IR injury, and cardiomyocytes challenged with hypoxia reoxygenation (HR) injury. GAS6 overexpression significantly improved cardiac dysfunction in mice subjected to myocardial IR injury, accompanied by reconciled mitochondrial dysfunction, oxidative stress, and apoptosis. In vitro experiments also observed a protective effect of GAS6 in cardiomyocytes. SIRT1 was found to function as a downstream regulator for GAS6/Axl signaling axis. Through screening a natural product library, a polyphenol natural compound catechin was identified to exhibit a protective effect by turning on GAS6/Axl-SIRT1 cascade. CONCLUSIONS: Together, our findings indicate that GAS6 emerges as a potential novel target in the management of myocardial IR injury and other related anomalies.

Dahuang-Wumei decoction protects against hepatic encephalopathy in mice: Behavioural, biochemical, and molecular evidence.

BACKGROUND: Disturbance of the blood‒brain barrier (BBB) and associated inflammatory responses are observed in patients with hepatic encephalopathy (HE) and can cause long-term complications. Dahuang-Wumei decoction (DWD) is a renowned traditional Chinese herbal medicine with a long history of clinical use and has been widely employed as an effective treatment for hepatic encephalopathy (HE). Despite its established efficacy, the precise mechanisms underlying the therapeutic effects of DWD have not been fully elucidated. PURPOSE: The present study aimed to comprehensively explore the potential effects and underlying molecular mechanisms of DWD on HE through an integrated investigation that included both in vivo and in vitro experiments. METHODS: In the present study, carbon tetrachloride (CCl4) and thioacetamide (TAA) were used to establish an HE model in mice. The therapeutic effects of DWD on liver injury, fibrosis, brain injury, behaviour, and consciousness disorders were evaluated in vivo. C8-D1A and bEnd.3 cells were used to construct a BBB model in vitro. The effects of DWD on proinflammatory factor expression, BBB damage and the Wnt/ß-catenin pathway were detected in vivo and in vitro. RESULTS: Our results showed that DWD can improve liver injury and fibrosis and brain damage and inhibit neurofunctional and behavioural disorders in mice with HE. Afterwards, we found that DWD decreased the levels of proinflammatory factors and suppressed BBB disruption by increasing the levels of junction proteins in vivo and vitro. Further studies verified that the Wnt/ß-catenin pathway may play a pivotal role in mediating the inhibitory effect of DWD on HE. CONCLUSION: These results demonstrated that DWD can treat HE by preventing BBB disruption, and the underlying mechanisms involved were associated with the activation of the Wnt/ß-catenin pathway and the inhibition of inflammatory responses.

Se-methylselenocysteine ameliorates mitochondrial function by targeting both mitophagy and autophagy in the mouse model of Alzheimer's disease.

Background: Alzheimer's disease (AD) exerts tremendous pressure on families and society due to its unknown etiology and lack of effective treatment options. Our previous study had shown that Se-methylselenocysteine (SMC) improved the cognition and synaptic plasticity of triple-transgenic AD (3 × Tg-AD) mice and alleviated the related pathological indicators. We are dedicated to investigating the therapeutic effects and molecular mechanisms of SMC on mitochondrial function in 3 × Tg-AD mice. Methods: Transmission electron microscopy (TEM), western blotting (WB), mitochondrial membrane potential (ΔΨm), mitochondrial swelling test, and mitochondrial oxygen consumption test were used to evaluate the mitochondrial morphology and function. Mitophagy flux and autophagy flux were assessed with immunofluorescence, TEM and WB. The Morris water maze test was applied to detect the behavioral ability of mice. Results: The destroyed mitochondrial morphology and function were repaired by SMC through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in 3 × Tg-AD mice. In addition, SMC ameliorated mitochondria by activating mitophagy flux via the BNIP3/NIX pathway and triggering autophagy flux by suppressing the Ras/Raf/MEK/ERK/mTOR pathway. SMC remarkably increased the cognitive ability of AD mice. Conclusions: This research indicated that SMC might exert its therapeutic effect by protecting mitochondria in 3 × Tg-AD mice.

Interfacial complexation between Fe3+ and Bi2MoO6 promote efficient persulfate activation via Fe3+/Fe2+ cycle for organic contaminates degradation upon visible light irradiation.

To address the observed decrease in efficiency during Fe2+-mediated persulfate (PDS) activation caused by slow electron transfer rates and challenges in cycling between Fe3+/Fe2+ states, we devised a strategy to establish interfacial complexation between Fe3+ and Bi2MoO6 in the presence of PDS. The proposed approach facilitates more efficient capture of photogenerated electrons, thereby accelerating the rate-limiting reduction process of the Fe3+/Fe2+ cycle under visible light irradiation and promoting PDS activation. The Bi2MoO6/Fe3+/PDS/Vis system demonstrates complete degradation of organic pollutants, including Atrazine (ATZ), carbamazepine (CBZ), bisphenol A (BPA), and 2,4-dichlorophenol (DCP) at a concentration of 10 mg/L within a rapid reaction time of 30 min. Radical scavenging experiments and electron paramagnetic resonance spectra (EPR) confirm that the sulfate radical (•SO4-) is the dominant species responsible for organic contaminant degradation. The real-time conversion process between Fe3+ and Fe2+ was monitored by observing changes in iron species forms and concentrations within the reaction system. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy verify the formation of a complexation between Fe3+ and Bi2MoO6, facilitating anchoring of Fe3+ onto material surface. Based on these findings, we propose a reliable mechanism for the activation reaction. This work presents a promising heterogeneous PDS activation method based on Fe3+/Fe2+ cycle for water treatment.

Identification of novel homozygous asthenoteratospermia-causing ARMC2 mutations associated with multiple morphological abnormalities of the sperm flagella.

PURPOSE: To identify the genetic causes of multiple morphological abnormalities in sperm flagella (MMAF) and male infertility in patients from two unrelated Han Chinese families. METHODS: Whole-exome sequencing was conducted using blood samples from the two individuals with MMAF and male infertility. Hematoxylin and eosin staining and scanning electron microscopy were performed to evaluate sperm morphology. Ultrastructural and immunostaining analyses of the spermatozoa were performed. The HEK293T cells were used to confirm the pathogenicity of the variants. RESULTS: We identified two novel homozygous missense ARMC2 variants: c.314C > T: p.P105L and c.2227A > G: p.N743D. Both variants are absent or rare in the human population genome data and are predicted to be deleterious. In vitro experiments indicated that both ARMC2 variants caused a slightly increased protein expression. ARMC2-mutant spermatozoa showed multiple morphological abnormalities (bent, short, coiled, absent, and irregular) in the flagella. In addition, the spermatozoa of the patients revealed a frequent absence of the central pair complex and disrupted axonemal ultrastructure. CONCLUSION: We identified two novel ARMC2 variants that caused male infertility and MMAF in Han Chinese patients. These findings expand the mutational spectrum of ARMC2 and provide insights into the complex causes and pathogenesis of MMAF.

Acute Exacerbation of Chronic Obstructive Pulmonary Disease Due to Carbapenem-Resistant Klebsiella pneumoniae-Induced Pneumonia: Clinical Features and Prognostic Factors.

Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis. Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360-57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112-65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037-1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006-1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%). Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient's condition more seriously and significantly increases the risk of death.

Multi-modal ultrasound multistage classification of PTC cervical lymph node metastasis via DualSwinThyroid.

Objective: This study aims to predict cervical lymph node metastasis in papillary thyroid carcinoma (PTC) patients with high accuracy. To achieve this, we introduce a novel deep learning model, DualSwinThyroid, leveraging multi-modal ultrasound imaging data for prediction. Materials and methods: We assembled a substantial dataset consisting of 3652 multi-modal ultrasound images from 299 PTC patients in this retrospective study. The newly developed DualSwinThyroid model integrates various ultrasound modalities and clinical data. Following its creation, we rigorously assessed the model's performance against a separate testing set, comparing it with established machine learning models and previous deep learning approaches. Results: Demonstrating remarkable precision, DualSwinThyroid achieved an AUC of 0.924 and an 96.3% accuracy on the test set. The model efficiently processed multi-modal data, pinpointing features indicative of lymph node metastasis in thyroid nodule ultrasound images. It offers a three-tier classification that aligns each level with a specific surgical strategy for PTC treatment. Conclusion: DualSwinThyroid, a deep learning model designed with multi-modal ultrasound radiomics, effectively estimates the degree of cervical lymph node metastasis in PTC patients. In addition, it also provides early, precise identification and facilitation of interventions for high-risk groups, thereby enhancing the strategic selection of surgical approaches in managing PTC patients.